NEUROLOGY – LABORATORY AND CLINICAL RESEARCH DEVELOPMENTS
SOCIETY, BEHAVIOUR AND EPILEPSY No part of this digital document may be reproduced, stored in a retrieval system or transmitted in any form or by any means. The publisher has taken reasonable care in the preparation of this digital document, but makes no expressed or implied warranty of any kind and assumes no responsibility for any errors or omissions. No liability is assumed for incidental or consequential damages in connection with or arising out of information contained herein. This digital document is sold with the clear understanding that the publisher is not engaged in rendering legal, medical or any other professional services.
NEUROLOGY – LABORATORY AND CLINICAL RESEARCH DEVELOPMENTS Additional books in this series can be found on Nova‘s website under the Series tab. Additional E-books in this series can be found on Nova‘s website under the E-book tab.
PSYCHOLOGY RESEARCH PROGRESS Additional books in this series can be found on Nova‘s website under the Series tab. Additional E-books in this series can be found on Nova‘s website under the E-book tab.
NEUROLOGY – LABORATORY AND CLINICAL RESEARCH DEVELOPMENTS
SOCIETY, BEHAVIOUR AND EPILEPSY
JAYA PINIKAHANA AND
CHRISTINE WALKER EDITORS
Nova Biomedical Books New York
Copyright © 2011 by Nova Science Publishers, Inc. All rights reserved. No part of this book may be reproduced, stored in a retrieval system or transmitted in any form or by any means: electronic, electrostatic, magnetic, tape, mechanical photocopying, recording or otherwise without the written permission of the Publisher. For permission to use material from this book please contact us: Telephone 631-231-7269; Fax 631-231-8175 Web Site: http://www.novapublishers.com NOTICE TO THE READER The Publisher has taken reasonable care in the preparation of this book, but makes no expressed or implied warranty of any kind and assumes no responsibility for any errors or omissions. No liability is assumed for incidental or consequential damages in connection with or arising out of information contained in this book. The Publisher shall not be liable for any special, consequential, or exemplary damages resulting, in whole or in part, from the readers‘ use of, or reliance upon, this material. Independent verification should be sought for any data, advice or recommendations contained in this book. In addition, no responsibility is assumed by the publisher for any injury and/or damage to persons or property arising from any methods, products, instructions, ideas or otherwise contained in this publication. This publication is designed to provide accurate and authoritative information with regard to the subject matter covered herein. It is sold with the clear understanding that the Publisher is not engaged in rendering legal or any other professional services. If legal or any other expert assistance is required, the services of a competent person should be sought. FROM A DECLARATION OF PARTICIPANTS JOINTLY ADOPTED BY A COMMITTEE OF THE AMERICAN BAR ASSOCIATION AND A COMMITTEE OF PUBLISHERS. Additional color graphics may be available in the e-book version of this book. Library of Congress Cataloging-in-Publication Data Society, behaviour and epilepsy / editors, Jaya Pinikahana, Christine Walker. p. cm. Includes index. ISBN 978-1-61761-385-2 (eBook) 1. Epilepsy--Social aspects. I. Pinikahana, Jaya. II. Walker, Christine, Ph. D. RA645.E64S636 2010 362.196'853--dc22 2010027274
Published by Nova Science Publishers, Inc. New York
Contents Preface
vii
About the Contributors
xi
Chapter I
Towards a Better Understanding of Living with Epilepsy: The Lived Experience of Seizures Jaya Pinikahana and Joanne Dono
Chapter II
Indicators of the Social Consequences of Epilepsy Kevin M. Brown
Chapter III
From Public to Personal: A Social and Ethnographic View of Epilepsy Lisa Francesca Andermann
1 17
29
Chapter IV
Quality of Life in Epilepsy Deirdre P. McLaughlin
43
Chapter V
Addressing the Treatment Gap in Epilepsy Christine Walker
59
Chapter VI
Health Literacy and the Outcomes of Care among Individuals with Epilepsy Ramon Edmundo D. Bautista and Maria Adela B. Bautista
Chapter VII
Epilepsy and Employment Malachy Bishop and Chung-Yi Chiu
Chapter VIII
Gender and Epilepsy: Clinical, Social and Psychological Impact R. Shallcross, R. L. Bromley and G. A. Baker
Chapter IX
Sociology and Epilepsy: Mind-body Medicalisation Peter Morrall
Chapter X
Crossing Continents: Meanings and Management of Epilepsy among People of Pakistani Origin Living in the UK Penny Rhodes and Neil Small
73 93
115 143
163
vi Chapter XI
Contents Adherence to Antiepileptic Drug Therapy across the Developmental Life-Span Avani C. Modi and Shanna M. Guilfoyle
Chapter XII
Social Competence and Children with Epilepsy K. Rantanen, K. Eriksson and P. Nieminen
Chapter XIII
Psychosocial Adjustment in Children with Epilepsy and Their Families Soraya Otero-Cuesta and Amador Priede
175 207
227
Chapter XIV
Perspectives on Depression in Epilepsy Adrian Palomino and Alexander W. Thompson
247
Chapter XV
Depression in People with Epilepsy Elizabeth Reisinger Walker and Colleen DiIorio
257
Chapter XVI
Epilepsy in the Elderly: Diagnostic Approach and Treatment Sophie Dupont, B. De Toffol, Marc Verny, and Caroline Hommet
289
Chapter XVII Use of Complementary and Alternative Medicine for Treatment of Epilepsy Reyna M. Durón and Kenton R. Holden
313
Index
331
Preface What is it like to live with epilepsy? How does this common neurological condition impact on the lives of those who have it and the people who care about them? How far have communities come in their understandings of epilepsy? These seemingly simple questions and the answers to them can be as diverse as the contexts in which they are framed. Consider for the moment the experience of a person with epilepsy in a remote mountain village in northern China, or the experience of another person in New York. How different their experiences are, will depend on their access to treatment, supplies of medicines, their own understanding of the condition and their families understanding as well as how many barriers their communities put in the way of them participating in their community. The authors cannot assume that the person surrounded by all the accoutrements of a modern industrial economy will have better outcomes to the person in remote China. Social and behavioral researchers need to analyse the multifaceted contexts of each society such as the social position each person holds in his or her own community; the resources they can access, including treatments and medicines; their cultural contexts; access to education and employment and how the attitudes of others around them create barriers or open the way to more opportunities. While those contexts make such questions complex, additionally epilepsy itself is no longer a simple diagnosis. Syndromes and seizure types of this condition will be experienced by people in the many different contexts in which they live their lives. A complex condition is experienced in an increasingly complex world. Questions such as those above must be tailored to suit each context in which they are asked. Thus the experience of the person with epilepsy in remote northern China may be quite different to the person in New York‘s experience, or it may indeed have some surprising similarities. But no single answer will be found. The predominant reason social and behavioural researchers are driven to explore epilepsy in relation to these contexts, is to improve people‘s lives. Clinical and pharmacological research in epilepsy has led to huge advances in the diagnosis and care of people with epilepsy, giving many people with epilepsy the opportunity to live safely in their communities, pursuing their own life choices. However, whereas in other diseases such as cancer, syphilis and tuberculosis, similar medical advances have served to remove long-held prejudices and change attitudes towards those with the conditions, this has not been the case with epilepsy. Parallel to these clinical advances in the care of epilepsy runs another body of deeply ingrained beliefs and behaviours-lived experience of social exclusion; social concepts
viii
Jaya Pinikahana and Christine Walker
of epilepsy, all of which form a layer of community attitudes. These beliefs and behaviours may sometimes be dismissed as prejudices or superstitions which can be ameliorated through better education on the physiological aspects of epilepsy. But they continue despite such efforts at education because they carry with them the weight of history and are deeply embedded in every society and every social structure. It is only by bringing them into the light of day they can be actively addressed through the application of policies and programs relating to social inclusion, or equal rights and social justice. This book takes as its point of departure that neurological medical research and pharmacological research has provided massive benefits to the care of people with epilepsy but it has not addressed the social needs of people with epilepsy. That is not its role. Now is the time to make the social advances commensurate with those neurological and pharmacological benefits. This can only be done by furthering The authors understanding of what such questions as the ones above, mean for people with epilepsy, their community and then using the results to inform policies and programs. Each chapter of this book discusses an aspect of epilepsy such as experience or its care and treatments within the specific social and behavioural contexts in which it is experienced. The aim is to highlight those policy and program areas where community leaders need to direct their energies to improve the lives of people with epilepsy. The first eight chapters concentrate on broad demographic issues while the next nine discuss more specific issues relating to the experience and care of epilepsy. Chapter I begins the journey with a study which documents one aspect of the lived experience of epilepsy-self-perceived warning signs, initial symptoms and triggers of epileptic seizures. Respondents to a survey who perceived they had warnings of seizures reported the techniques they undertook to avoid those seizures occurring. These results demonstrate some respondents were able to recognise warning signs, initial symptoms and triggers of seizures, and some were able to stop seizures. This suggests scope for developing interventions, such as promoting avoidance of high risk triggers, to supplement existing treatments of epilepsy. Chapter II presents Australian data that for the first time estimate the proportion of the population affected by epilepsy in an inclusive sense, that is provide combined figures for both those suffering epilepsy and their household members. It is argued that the key issues for the better understanding of the realities and determinants of living with epilepsy can be set out in three major research strands: the need for (more) accurate prevalence data; the fuller use of existing official statistics/data sources and quality of life issues. These data form the basis for more accurate and informed debates on the role of stigma and discrimination in epilepsy. Chapter III is a review of literature from the social sciences on the lived experience of epilepsy. It includes a discussion of the influences on public perceptions and examines stigma relating to epilepsy through some examples from current literature, the arts and the Internet. The author argues that while there has been progress in certain areas of public education, stigma reduction and perception around epilepsy, work still remains to be done. She identifies health disparities and immigrant and newcomer health as areas of particular concern. Chapter IV continues with the themes from previous chapter, by examining the concept of quality of life (QOL) and the psychosocial issues that affect QOL of people with epilepsy. From the perspective of adult life span, the chapter looks at the functioning of adults and
Preface
ix
older adults with epilepsy and discusses the differences in the manifestations and impact of epilepsy on QOL across the adult lifespan. Chapter V uses a political economy of health approach to explore the treatment gap in epilepsy across both developing and developed economies. This chapter undertakes an analysis of health systems and health financing that contribute to the treatment gap and looks at some of the health systems reforms that would assist in closing the treatment gap. Chapter VI represents another under-developed area where epilepsy is concerned. Health literacy is known to be associated with quality of life and optimal disease management. However little is known of health literacy and epilepsy and there have been few attempts to improve health literacy among people with epilepsy and their caregivers. The authors argue that models may be adopted from other conditions and new models developed in order to optimize epilepsy care and accelerate the societal integration of these individuals. Chapter VII addresses the important issue of unemployment and underemployment of people with epilepsy. Despite improved treatments and legislation to improve employment opportunities for people with disabilities, adults with epilepsy have relatively low levels of employment. The complex factors involved in employment of people with epilepsy is viewed from an international perspective exploring the barriers to employment as well as the value of epilepsy-specific employment programs. Chapter VIII argues that gender is an important aspect to consider in epilepsy care though research often treats people with epilepsy as a homogenous group. Healthcare professionals need to be aware of gender differences in the management of people with epilepsy and information needs to be tailored to suit both genders. Chapter IX takes the reader on a different journey with a critical examination of the ‗medicalisation‘ of epilepsy and its status as both a medical condition and a stigmatized condition. The author argues that epilepsy attracts both stigmatisation and medicalisation of the mind and body. Interpersonal and social reaction to epilepsy results in subjective experiences of ‗shame‘, ‗spoiled identity‘, ‗discredited status‘, and ‗hidden distress‘. However, the author concludes that people with epilepsy make the trade-off of living with a level of stigma in order to benefit from the effective management achieved under ‗mind-body medicalisation.‘ Chapter X shows another level of complexity regarding Western medicine. A Pakistani community in the United Kingdom combines traditional beliefs and practices with a strong belief in the efficacy of Western medicine. The resulting hybrid experience, the authors argue, is likely to be a characteristic of migrant communities worldwide. Chapter XI undertakes an evaluation of the problem of adherence to antiepileptic drugs, which is largely underappreciated and unrecognized. The authors explore the current state of adherence research in both adult and paediatric epilepsy. They evaluate adherence measurement issues, how predictors of adherence are measured and interventions to promote adherence as well as looking at directions for future research. Chapter XII reviews social issues associated with childhood epilepsy. Children with epilepsy are at risk for developing behavioral problems and impaired social competence. After summarising definitions of social competence, this chapter focuses on current knowledge about social competence, including behavior problems related to epilepsy. The authors discuss the need for early assessment of social competence in children and that it is important to support the development of appropriate psychosocial skills to avoid long-lasting social and behavioural problems.
x
Jaya Pinikahana and Christine Walker
Chapter XIII continues the focus on children with epilepsy and their families. While the problems present in children with epilepsy are similar to those in the general population, there are some symptoms relatively specific to children with epilepsy, for instance attention problems, social problems and thought problems. These are more likely to be related to family factors, including family coping with illness, parent-child relationships and stress. The authors argue that future research and interventions should include the use of psychiatric interviews and direct observation to gather information on psychopathology instead of assessments exclusively relying on scales and questionnaires, while neuropsychological assessment and neurodevelopmental perspectives are essential to develop models explaining complexity of relationships between epilepsy, brain, and behaviour. Multidisciplinary approaches are also necessary to develop interventions in such a complex area. Chapter XIV turns readers‘ attention to depression in epilepsy, a common comorbidity. This chapter looks at the relative values of different approaches to depression, the purely clinical, the biopsychosocial and the ‗four perspective‘ approach which attempts to guide treatment for depression where it is interconnected with multiple factors including seizures, cognitive problems and side-effects of anti-epileptics. Chapter XV continues with depression, this time focussing on the barriers and facilitators for treatment of depression among people with epilepsy. When depression is recognised intervention can be made to treat it. The literature on depression and epilepsy is examined in this chapter, with regard to the factors influencing the diagnosis and treatment of depression among people with epilepsy, addressing barriers to treatment, and approaches for treating depression in people with epilepsy. The chapter concludes with suggested future research. Chapter XVI considers epilepsy in the elderly, an important area in view of the ageing of the population in developed countries. Epilepsy is particularly complex in older people since they are more likely to have co-morbidities than younger individuals. At the same time epilepsy may be confused with other conditions such as stroke or dementia thus delaying the diagnosis. Treatment must be adapted to the particular susceptibilities of elderly people. Chapter XVII finally addresses the common usage of complementary and alternative medicines (CAM) for epilepsy throughout the world. The authors consider herbal medicines, acupuncture, prayer, music and meditation as well as diet-based treatments. CAM use is associated with the belief it is safe and effective, as well as higher levels of education. It may also be associated with dissatisfaction with AEDs or their lack of availability. At the same time in cultures where epilepsy is held to be caused by supernatural forces CAM use is often the preferred treatment. The authors argue there are five possible outcomes associated with CAM use and some of these outcomes may be detrimental for the individual. The authors consider open discussion about CAM should be promoted in association with education programs and access to treatment. Research into adjuvant therapies might also determine which CAM are affective. Jaya Pinikahana and Christine Walker
About the Contributors Gus A. Baker, PhD, FBPsS, is a Consultant Clinical Neuropsychologist, Professor of Clinical Neuropsychology in the University Division of Neurosciences at the University of Liverpool, UK. He obtained his master‘s degree and his PhD from the University of Liverpool, both in the field of clinical psychology/neuropsychology (medicine). The focus of Professor Baker‘s research is understanding the impact of chronic diseases, especially epilepsy. One outcome of this research, supported by Wellcome and Medical Research Council grants, has been the development of methodology to quantify the different effects of treatment. This methodology has been used to assess the efficacy of new drug and surgical treatments for epilepsy. An author or co-author of more than 200 books, chapters, and articles—appearing in such peer-reviewed journals as the Epilepsia, Epilepsy and Behaviour, Neurology and Epilepsy Research and The New England Journal of Medicine—on the psychological and neuropsychological consequences of epilepsy, Professor Baker is also a member of the editorial board of Epilepsy and Behavior and Seizure. Professor Baker has served as a member of the International League Against Epilepsy (ILAE) commission on the burden of epilepsy and the IBE Research Commission. The latter commission advises the ILAE on all matters pertaining to outcome measures for use in clinical practice and research. Underscoring the international scope of his endeavors, he has served as a member of the Center for Disease Control and Prevention‘s working party for epilepsy. Professor Baker is a past recipient of the Ambassador for Epilepsy Award of the ILAE/International Bureau for Epilepsy (IBE) in recognition of his international contribution to activities advancing the cause of epilepsy. In 2001, Professor Baker was awarded the British Psychological Society lifetime award for distinguished contribution to professional psychology in recognition of his services to epilepsy. Professor Baker is also a member of the Global Campaign Against Epilepsy, a World Health Organization/ILAE/IBE initiative. Colleen Di Iorio, PhD, RN, FAAN, is Professor in the Department of Behavioral Sciences and Health Education at Rollins School of Public Health at Emory University in Atlanta, Georgia, U.S.A. Dr. Di Iorio earned a doctoral degree in nursing research and theory development from New York University, a masters degree in nursing from New York University and a baccalaurate in nursing from the University of Iowa. Her work in epilepsy self-management has included the study of psychosocial factors associated with medication adherence and self-management practices and factors associated with depression, stigma, and quality of life among those with epilepsy. Dr. Di Iorio has been involved in the development of the Managing Epilepsy Well (MEW) Network and serves as the director of the MEW
xii
About the Contributors
Network coordinating site at Emory University. Recently, she has developed an Internetbased, theory driven self-management program for promoting self-management among people with epilepsy. The program named WebEase is currently being evaluated in a randomized controlled trial funded by the United States Centers for Disease Control and Prevention (CDC). She received the Distinguished Nurse Scholar Award from New York University and the Distinguished Alumni Award from the University of Iowa. Jaya Pinikahana MSc, PhD is Principal Social Researcher/Head, research division at the Epilepsy Foundation of Victoria, Australia. Since completing his PhD in 1990, he has gained research experience in numerous areas including chronic illness, mental illness and ageing. He was the chief investigator for a WHO funded study on malaria transmission in Sri Lanka in the early 90s. He swapped life in Sri Lanka as a senior university lecturer to being a senior researcher in Western Australia. Prior to coming to the Epilepsy Foundation of Victoria, he worked as a research fellow at the National Ageing Research Institute in Melbourne and as a senior research fellow in nursing at Monash University, Victoria. He has published more than 30 papers in national and international journals. Jaya has been extensively involved in teaching general sociology, health sociology, and research methods for arts, medical and nursing students in Sri Lanka, the United Kingdom, New Zealand and Australia. He is a regular reviewer of manuscripts for health and nursing journals and funding bodies. He is a co-editor of Social Epileptology: Understanding Social Aspects of Epilepsy published by Nova Science Publishers in 2009. Joanne Dono has a Honours degree in Psychology from Deakin University, Melbourne and is currently working towards obtaining a Masters degree in Organisational Psychology at the University of Adelaide. She was employed by the Epilepsy Foundation of Victoria as a research assistant while the research regarding subjective experiences of seizures was carried out. Christine Walker PhD is a member of the Management Committee of the Epilepsy Foundation of Victoria and the President of Epilepsy Australia. She is an experienced social researcher specializing in the area of health policy and health services that relate to the needs of people with chronic illnesses. She is currently a Chief Investigator in several Australian National Health and Medical Research Council research grants on diabetes and heart disease. Having conducted research into the value of chronic disease self-management as a strategy to prevent chronic diseases, she has published the results in national and international journals. More recently she has written several reports on the status of epilepsy in the Australian community. She has co-edited a book on chronic illness which presents the most recent thinking about approaches to the care of people with chronic illnesses in Australia. In April 2007 Christine received an award from the University of New South Wales Research Centre for Primary Health Care and Equity for her contribution to chronic disease care. She is currently the CEO of the Chronic Illness Alliance, Australia. She is a co-editor of Social Epileptology: Understanding Social Aspects of Epilepsy published by Nova Science Publishers in 2009. Ramon Edmundo D. Bautista, M.D., M.B.A. is Associate Professor of Neurology and Director of the Comprehensive Epilepsy Program, University of Florida Health Science Center in Jacksonville, Florida. Dr. Bautista graduated from the University of the Philippines College of Medicine and completed his residency in neurology at Washington University in St. Louis, Missouri. He did post-graduate training in clinical neurophysiology and epilepsy at Emory University in Atlanta, Georgia and Yale University in New Haven, Connecticut. Dr.
About the Contributors
xiii
Bautista is a member of the American Academy of Neurology and the American Epilepsy Society. His research interests include clinical epilepsy and neurophysiology as well as health-related outcomes of epilepsy care. His publications can be found in various peerreviewed journals such as Neurology, Epilepsia, Epilepsy and Behavior, and Seizure. Maria Adela B. Bautista, M.D. obtained her medical degree from the University of the Philippines. She finished a research internship at the Jacksonville Health and Transition Services program at the University of Florida Health Sciences in Jacksonville, Florida and is currently completing a Masters degree in Public Health at the University of North Florida. Avani C. Modi, PhD, is Assistant Professor at the University of Cincinnati College of Medicine and within the Center for the Promotion of Adherence and Self Management in the Division of Behavioral Medicine and Clinical Psychology at Cincinnati Children's Hospital Medical Center. Dr Modi's program of research focuses on adherence to pediatric medical regimens, including the measurement of adherence and identifying barriers to effective disease management. Dr Modi, received a K23 Career Development Award from the National Institutes of Health (K23 HDO57333) documenting patterns of adherence in children with new-onset epilepsy (ages 2-12 years), developing a surrogate marker of adherence and identifying predictors of adherence that will serve as the focus of future intervention trials to improve adherence. In addition, Dr Modi is a co-investigator on grants examining 1) longitudinal outcomes in adolescents with extreme obesity undergoing bariatric surgery and 2) designing and implementing a web-based assessment of barriers to adherence for children and adolescents with sickle cell disease. Shanna M. Guilfoyle, PhD, is a Postdoctoral Fellow in the Center for Adherence Promotion and Self-Management at Cincinnati Children‘s Hospital Medical Center. She completed her doctoral work in Clinical Psychology with emphasis on Child Clinical Psychology at the Kent State University and internship within the Division of Behavioral Medicine and Clinical Psychology at Cincinnati Children's Hospital Medical Center. Her research interests include examining parenting and family factors and their relative impact on adherence to pediatric treatment regimens and clinical outcomes in children managing chronic illnesses. Elizabeth Reisinger Walker, MAT, MPH is a doctoral student in the Department of Behavioral Science and Health Education in the Rollins School of Public Health at Emory University, Atlanta, Georgia, U.S.A. Ms. Walker earned a Master of Public Health from Emory University, a Master of Arts in Teaching from Johns Hopkins University, and a baccalaureate in biology and history from the University of Rochester. She is a research assistant on WebEase, a theory-driven, web-based, self-management program for people with epilepsy. She has presented at the American Public Health Association annual conference and is an author on several peer-reviewed articles. Ms. Walker has received a Woodruff Fellowship from Emory University for her MPH and doctoral studies and several awards from the University of Rochester for student leadership and academic excellence. Deirdre McLaughlin, PhD, is a Research Fellow with the Men, Women and Ageing study at the University of Queensland, School of Population Health. She holds a Bachelor of Behavioural Science, Bachelor of Science and PhD in psychology. Deirdre‘s background is in health psychology and her research has included health related quality of life issues and coping with chronic illness. Her doctoral thesis examined the impact of epilepsy on the quality of life of older adults. Deirdre has also worked with Epilepsy Queensland Inc examining the impact of chronic disease on families and has produced a report entitled
xiv
About the Contributors
―Living in the Shadows: Families who care for children with uncontrolled epilepsy or epilepsy and another disability‖. Deirdre is a registered psychologist and is a member of the Australian Psychological Society and is the current national treasurer and state secretary of the Psychology of Ageing Interest Group of the APS. Rebekah Shallcross, BSc, is currently conducting research at the University of Liverpool, UK as part of her Doctorate degree. She obtained her undergraduate psychology degree from Royal Holloway and Bedford New College, The University of London, UK. Ms Shallcross‘ research compares the developmental, cognitive and behavioural outcomes of children exposed in utero to Antiepileptic medications, which she has presented at various national and international conferences. Rebecca L. Bromley, PhD, is currently a Research Associate at the University of Liverpool, UK. She obtained her undergraduate and PhD degree from the University of Liverpool, UK, both in the field of psychology. Her main area of interest is the cognitive, behavioural and neurodevelopmental profile of children exposed in utero to antiepileptic medication, and has published several articles within this area. She has received the American Epilepsy Societies and the ILAE young investigators travel awards to present her work internationally. Recently, she was also successful in securing a Epilepsy Research UK grant in order to carry out further research regarding cognitive outcome and in utero exposure to the second generation antiepileptic medications, furthering and expanding our knowledge in this very important area. Neil Small is Professor of Health Research in the School of Health Studies, University of Bradford, UK. He is a sociologist with a long standing interest in health inequalities and in chronic and life limiting illness. His current research is on ethnicity and health and is centred on the large scale birth cohort study, Born in Bradford. Penny Rhodes is Senior Research Fellow at the Bradford Institute for Health Research, Bradford Hospitals NHS Teaching Trust. Most of her work has been in the field of health and social care, with a particular focus on chronic illness and patient/service user involvement in the research process. She is currently working with the Yorkshire Quality and Safety Research Group. Malachy Bishop is Professor of Rehabilitation Counseling at the University of Kentucky. Dr. Bishop completed his doctoral study in Rehabilitation Psychology at the University of Wisconsin-Madison. He conducts research primarily in the areas of quality of life, adaptation to disability, and the psychosocial aspects of living with neurological conditions including epilepsy, multiple sclerosis, and brain injury. He is a member of the Epilepsy Foundation of America‘s Professional Advisory Board and has served on the American Epilepsy Society‘s Task Force on Employment Issues. He has authored over 50 articles in rehabilitation and related professional journals. Chung-Yi Chiu, PhD, is Assistant Professor in the Department of Rehabilitation Counseling, School of Health Professions, University of Texas Southwestern Medical Center at Dallas. Dr. Chiu received her PhD in Rehabilitation Psychology from the University of Wisconsin-Madison and a master‘s degree in occupational therapy from the National Taiwan University. She is currently a consulting editor for the Australian Journal of Rehabilitation Counseling and serves on the board of the North Texas Area Rehabilitation Association.
About the Contributors
xv
Soraya Otero-Cuesta, MD, PhD is a Consultant in Child and Adolescent Psychiatry, Child and Adolecent Psychiatry and Psychology Unit, Department of Psychiatry, University Hospital Marques de Valdecilla, Santander, Cantabria, Spain. Associated Lecturer on Child and Adolescent Psychiatry, School of Medicine, University of Cantabria, Spain Amador Priede is a Clinical Psychologist, Child and Adolecent Psychiatry and Psychology Unit, Department of Psychiatry, University Hospital Marques de Valdecilla, Santander, Cantabria Lisa Andermann MPhil, MDCM, FRCPC is Assistant Professor in the Department of Psychiatry at the University of Toronto and psychiatrist at Mount Sinai Hospital, where she works in the Psychological Trauma Clinic as well as the Ethnocultural Assertive Community Treatment Team. She is also a psychiatric consultant with the Canadian Centre for Victims of Torture. She has a longstanding interest in social aspects of epilepsy and has done research on epilepsy in developing countries, with fieldwork in Ethiopia. Together with Dr. Steven Schachter, she co-edited The Brainstorms Village: Epilepsy in our world (2003); republished by Oxford University Press in 2008 as Epilepsy in our world: Stories of living with seizures from around the world), a collection of first-person narratives written by people with epilepsy from over 20 countries. She has an undergraduate degree in Anthropology from McGill University, where she completed her medical studies, and a graduate degree in Social Anthropology from Cambridge University. Sophie Dupont is Associate Professor, ―Maître de conferences‖, in the Clinical Epilepsy Department at La Pitié-Salpêtrière Hospital (Paris, FRANCE). She has specialized in clinical epilepsy, antiepileptic clinical trials, and neuroimaging. She also works at the anatomy department of the Pitiè-Salpêtrière University and the CRICM research unit located in Paris. Dr Dupont trained in adult neurology and neuroradiology at the Pitiè-Salpêtrière Hospital. Dr Dupont received her PhD degree in neuroscience at the university of Paris VI. Her research interests focus on neuroimaging and memory in adult epilepsy patients. She is the author or co author of several clinical and research papers in such journals as Brain, Neurology, Annals of Neurology. Bertrand de Toffol PhD is Professor of Neurology, head of the Neurology Department at Tours Hospital. He has specialized in neurology and psychiatry and he is past president of the French Chapter of the International League Against Epilepsy (ILAE). He has special interest in both psychiatric disturbances in epilepsy and clinical neurophysiology. Prof de Toffol received his PhD degree in neuroscience at the university of Paris VI in 1991. He is the author or co-author of several books devoted to epileptology and of more than 130 papers indexed in PubMed. Marc Verny PhD is Professor of Geriatry and he is chief of the Geriatric Department at La Pitié-Salpêtrière Hospital. He has specialized in neurological diseases in the elderly with particular attention to the interaction between neurological diseases and systemic pathologies. He has a special interest in dementia. Pr VERNY trained in adult neurology and geriatry at the Pitiè-Salpêtrière Hospital. He has received his PhD degree in neuroscience at the university of Paris VI. His research interests focus on dementia in older patients, notably diagnostic difficulties and neuropathologic correlations. He is the author or coauthor of several clinical and research papers in such journals as Brain, Neurology, Annals of Neurology, Journal of American Geriatric Society, Age and Ageing.
xvi
About the Contributors
Caroline Hommet PhD is Professor of Geriatrics and the chief of the department of Neuropsycholology in Aging and the Regional Memory Center in Alzheimer Disease and related disorders. Her special interest concerns neurological diseases in the elderly, particularly dementia. Pr Hommet received her PhD degree at the university of Tours. Her research interests focus on dementia, neuropsychology, clinical epilepsy, and neuroimaging. She also works at the INSERM U 930 research unit (Imaging and Brain) located in Tours. She is the author or co-author of several clinical research papers in journal‘s such as Journal of American Geriatric Society, Neuropsychologia, Demntia and Geriatric Cognitive Disorders or Neurosciences and Biobehavioral review. Kevin M Brown, PhD is a Sociologist who has researched and published widely in the areas of community association, the third sector, social capital and social exclusion. In 2006-7 he was the foundation researcher at the Epilepsy Foundation of Victoria where he helped initiate and grow a social research agenda. Current research includes comparative forms of active citizenship, Asian cosmopolitanism, the social effects of community sport involvement and the hidden costs of volunteering. He is currently a senior lecturer in sociology at Deakin University, Melbourne where he is also deputy director of the Centre for Citizenship, Development and Human Rights at Deakin University. He is the immediate past President of the Australia and New Zealand Third Sector Research Association. Adrian Palomino, MD is a first-year internal medicine resident at the University of California at Davis Medical Center in Sacramento, CA. Prior to moving into internal medicine training, he completed one year of psychiatry training at the University of Washington. His academic interests include the intersection between medical, neurological, and psychiatric illness, and the treatment of substance abuse in the primary care setting. Alexander W Thompson, MD, MBA, MPH is an attending inpatient and consultation – liaison psychiatrist at the Texas AandM affiliated Scott and White Hospital in Temple, TX. He completed a health services research fellowship at the University of Washington after completing psychiatry training at Johns Hopkins Hospital. His clinical and research interests include the management of psychiatric aspects of neurological disorders. Kati Rantanen MA has specialised in clinical neuropsychology (Lic.A., 2007). During 1999-2005 she worked as a psychologist at the municipal family guidance center. Currently, from 2007 she has been working as a psychologist in the Department of Pediatrics, Tampere University Hospital and at the same time from 2004 she has been working as a clinical neuropsychologist and researcher in the Psychology Clinic at the Department of Psychology, University of Tampere. She is preparing her academic dissertation focusing on neurocognitive functioning and social competence of preschool children with epilepsy. Kai Eriksson MD, PhD is currently the head of the Pediatric Neurology Unit, Tampere University Hospital and Pediatric Neurology Research Group, Medical School, University of Tampere. He specialised in pediatric neurology at Tampere University during the 1990s and his academic dissertation in 1998 focused on epidemiological, clinical and treatment aspects of childhood epilepsy and status epilepticus. During the 1990s he was visiting researcher at Stanford University Medical School, USA and at the Hospital for Sick Children, Great Ormond Street, London, UK. After that he has acted as an associate professor of pediatric neurology at the Medical School at the University of Tampere from 1999-2003 and subsequently a professor of pediatrics from 2004-2006. Since 2007 he has held the current posts and authored several book chapters and original articles focusing on epidemiology, treatment and neurocognitive as well as social aspects of childhood epilepsy. He is currently
About the Contributors
xvii
the chair of the Finnish National Guideline Group for pediatric epilepsy and Finnish Pediatric Neurology Society. Pirkko Nieminen PhD, specialised in clinical neuropsychology in 2002 and in psychology of acute crisis in 2004. From 1971-1988 she worked as assistant, senior assistant and lecturer in the Department of Psychology, University of Tampere. After that she worked as a psychologist in the Department of Pediatrics, Tampere University Hospital and at the same time in 1990-2004 she had a post as lecturer or associate professor in Psykonet, the University Network of Psychology. Since 2005 she has been working as senior lecturer in the psychology department, University of Tampere, being the head of the Psychology Clinic. Her research work has focused on neurocognitive and social aspects of neurological diseases and rehabilitation of disabled children. Peter Morrall PhD is Senior Lecturer in Health and Sociology at the University of Leeds, UK. Peter's academic interests encompass madness, murder, sociology and health, crime and health, psychotherapy, sexuality, and thinking. His recent books include 'Murder and Society' (Wiley, 2006), The Trouble With Therapy: Sociology and Psychotherapy (McGraw-Hill, 2008), Sociology and Health: An Introduction (Routledge, 2009). Kenton R. Holden, M.D. is Professor of Neurosciences (Neurology) and Pediatrics at the Medical University of South Carolina, Charleston, South Carolina, USA where he also is the Director of Medical Student Clinical Neurosciences Education. In addition, he is Senior Clinical Research Neurologist at the Greenwood Genetic Center, Greenwood, South Carolina. He received his MD at the Medical College of Virginia, Pediatric residency at the Johns Hopkins Hospital, and Fellowship training in Child Neurology at the National Institutes of Health, Bethesda, Maryland. He has authored or co-authored more than 150 articles, abstracts, and book chapters. Many of these articles appear in peer-reviewed journals such as The New England Journal of Medicine; Epilepsia; Pediatrics; Journal of Pediatrics; Epilepsy and Behavior; Journal of Child Neurology; Developmental Medicine and Child Neurology, Seizure-European Journal of Epilepsy, American Journal of Medical Genetics, and American Journal of Human Genetics with aspects of epilepsy as one primary focus. He is a member of the American Epilepsy Society, the Child Neurology Society, and the International Child Neurology Association. He is also a member of the editorial board of the Journal of Child Neurology. In addition to his patient care responsibilities, Dr. Holden has participated in numerous funded clinical research projects on epilepsy including neonatal seizures, clinical evaluation of new anticonvulsants, and improving care of institutionalized people with epilepsy. Dr. Holden received the First Annual International Visiting Professor Award from the Child Neurology Society and the Fritz E. Dreifuss International Travel Award from the Epilepsy Foundation (USA) for travel to the developing country of Honduras, Central America to help establish a Neurology training program and participate in research on epilepsy and other neurologic illnesses. Reyna M. Durón, M.D. is a Neurologist, Epileptologist, and Clinical Neurophysiologist trained at the National Autonomous University of Honduras, Tegucigalpa, Honduras, Central America and the University of California at Los Angeles. She is a Consultant for several neurology services in Honduras and member of the Professional Advisory Board of the Epilepsy Foundation of Greater Los Angeles. She is the founder of epilepsy clinics in three cities of Honduras and has been part of educational projects on epilepsy for the Latino community in Los Angeles, California, USA. As a clinical research scientist, Dr. Durón has focused on the epidemiology, anthropology, and genetics of the epilepsies. She is part of
xviii
About the Contributors
several research teams on epilepsy inside and outside of Honduras. She has promoted several studies on the anthropological aspects of the epilepsies in several ethnic groups in Honduras. As part of an international study group, she has also participated in genetic studies of absence and myoclonic epilepsies. Dr. Durón has co-authored more than 20 publications on neurological subjects, predominantly on epilepsy. These articles and chapters have been published in peer-reviewed journals such as Epilepsia, Epilepsy and Behaviour, Neurology, Brain and Advances of Neurology. As Director of the Honduran Medical Journal, she has contributed to the socialization of updated concepts about epilepsy diagnosis and management, as well as neglected issues such as quality of life and access and adherence to epilepsy treatment.
In: Society, Behaviour and Epilepsy Editors: Jaya Pinikahana and Christine Walker
ISBN 978-1-61761-001-1 © 2011 Nova Science Publishers, Inc.
Chapter I
Towards a Better Understanding of Living with Epilepsy: The Lived Experience of Seizures Jaya Pinikahana 1 and Joanne Dono 2 1. Principal Social Researcher, The Epilepsy Foundation of Victoria, Australia 2. Post graduate student, University of Adelaide, South Australia, Australia
Abstract The study aimed to document self-perceived warning signs, initial symptoms, and triggers of epileptic seizures and techniques to control seizures for people with epilepsy, and to establish patterns in these self-reported experiences of epilepsy in relation to age, gender and seizure type. Of the 338 people with epilepsy who had registered interest in participating in social research, 225 returned a self-report questionnaire (66% response rate) that contained information regarding demographic characteristics, living with epilepsy, and self-perceived warning signs, initial symptoms, triggers of seizures and techniques to control seizures. Of 225 respondents, 195 (86.6%) experienced at least one initial symptom prior to a seizure and 202 (89.8%) experienced at least one seizure trigger. Gender analysis of triggers revealed that females differed from males regarding seizures triggered by low blood sugar, dieting, fasting, touch and female specific triggers (menstruation, pregnancy and ovulation). Respondents reported tiredness as the most frequent trigger (65.3%), followed by stress (64%) and sleep deprivation (55.1%). Many respondents (63.6%) reported that they could predict seizure occurrence, with 91 (40.4%) also indicating that family members could predict seizure occurrence. A total of 157 (69.8%) respondents had tried at least one of 12 possible seizure avoidance techniques, with resting and medication the most frequently reported. Finding that respondents were Correspondence: Dr Jaya Pinikahana BA Hons, MSc, PhD. Principal Social Researcher/Head, Research Division, The Epilepsy Foundation of Victoria, No 818, Burke Road, Camberwell, Victoria, 3124, Australia. Tel: 03 9805 9125; Fax: 03 9882 7159. Email:
[email protected].
2
Jaya Pinikahana and Joanne Dono able to recognise warning signs, initial symptoms and triggers of seizures, and some were able to stop seizures provides scope for developing interventions, such as promoting avoidance of high risk triggers, which supplement existing treatments of epilepsy.
Introduction Epilepsy is a common neurological disorder that affects people of all ages, ethnicity and levels of social status, yet the subjective experiences associated with living with epilepsy are generally not well understood. Epilepsy encompasses a number of seizure types, and characteristic conditions that are not only important diagnostically, but also appear to influence the subjective experience of having epilepsy. Indeed, the heterogeneous nature of epilepsy means that a person‘s experience of epilepsy can vary over time and can differ from others who have a similar neurological condition. One of the most debilitating aspects of epilepsy is the perceived lack of control over when a seizure may occur, and the dangers associated with loss of awareness (e.g. when driving or swimming; Litt and Echauz, 2002). Hayden et al., (1992) examined epilepsy patient perceptions and found that only 4.3% of respondents indicated that nothing worried them about having epilepsy. Furthermore, the most common concerns were seizure related, with 26.9% of respondents stating that the unpredictability, severity or control of their seizures was their main concern. While seizures are perceived as random events by many, it is also acknowledged that patterns do exist, and seizures can be promoted or inhibited by internal or external stimuli (Spatt et al., 1998). In fact, warning signs and initial symptoms of epilepsy have been recognised for centuries (e.g. Gowers, 1885). By the early 20th century, protective activities such as monitoring hydration levels, dietary ketosis, and controlling excessive emotional stress and fatigue were advocated as therapeutic measures (Aird and Gordon, 1993). The dietary and lifestyle methods of intervention declined following the improvement in antiepileptic medication and brain monitoring technology. However, the recognition that antiepileptic medication and surgery does not work for many people with epilepsy has renewed interest in using other therapeutic methods (Nakken et al., 2005). More recently, Haut et al., (2007b) found that patients can identify periods of increased risk of seizure. Warning signs that precede a seizure are called premonitory symptoms, and can occur from 10 minutes to several days in advance. Premonitory symptoms can be sudden and momentary, such as being in a dreamy state, body jerks, and giddiness, or continuous, such as irritability, lethargy and emotional changes (Hughes et al., 1993). Simple partial seizures (including auras) can also be considered a warning sign for many people who also experience other types of seizures (e.g. tonic clonic; Rajna et al., 1997). Of the few studies published on premonitory symptoms, the findings indicate that between 7% and 50% of the epilepsy population may experience at least one symptom (Hughes et al., 1993; Rajna et al., 1997; Schulze-Bonhage et al., 2006). A total of 60 different symptoms were reported in a study conducted by Hughes et al. (1993). While most seizures appear to occur spontaneously, they may be precipitated by a variety of endogenous or exogenous factors (Fenwick and Brown, 1989; Nakken et al., 2005). Precipitants can be defined as ‗those circumstances that precede the onset of an epileptic attack and are considered by both patient and neurologist to be a possible explanation for why
Towards a Better Understanding of Living with Epilepsy
3
the seizure happened when it did‘ (Nakken et al., 2005). According to Aird and Gordon (1993), seizure precipitants can be seizure inducing if they are environmental or endogenous in origin, or seizure-triggering if they are chemical or physiological stimulation factors. Flashing lights that can induce a seizure in a person with epilepsy is a well-known example of a seizure precipitant. As epilepsy is a group of heterogeneous disorders, each with a different physiology, seizure precipitants can vary widely amongst individuals (Fang et al., 2008). Few published studies exist on the subject of subjective experiences of seizure precipitants. Of those studies that have investigated seizure precipitants, the percentages of people with epilepsy experiencing at least one type ranges from 29% (N=148; Hughes et al., 1993) to 92% (N=75; da Silva Sousa et al., 2005). Furthermore, despite the variety in patients in terms of location, living situation and seizure type, the most common seizure precipitant across a number of studies is ‗stress‘ (see Table 1). Other precipitants that also rated highly include sleep deprivation, fever, tiredness, menstruation and missed medication. Table 1. Summary of studies that have investigated seizure precipitants Author
N
Most common precipitant (% of participants)
Country
100 194 79 75
% with seizure precipitants 83 63 92
Antebi and Bird (1993) Aziz et al. (1994) Cull et al. (1996) da Silva Sousa et al. (2005) Dawkins et al. (1993) Fang et al. (2008) Fisher et al. (2000) Frucht et al. (2000) Hart and Shorvon (1995) Hayden et al. (1992) Jarvie et al. (1993) Løyning et al. (1993) Nakken et al. (2005)
Anxiety (66%) Fever (26%) Stress (38%) Stress (83%)
UK Pakistan UK Brazil
29 120 818 400 1628
59 62 83 62 49
Interpersonal stress (55%) Fever/illness (32%) Stress (60%) Stress (30%) Stress (28%)
UK Taiwan US US UK
475 79 64 1677
81 26 82 53
Stress (41%) Stress (42%) Emotional stress (21%)
Spatt et al. (1998) Spector et al. (2000)
149 100
72 90
Sperling et al. (2008) Tan et al. (2005) Unsworth (1999)
200 40 82
65 32 37
Stress (34%) Tense/anxious/ worried/stressed (53%) Stress (49%) Stress (10%) Stress (-)
Australia UK US US, Denmark, Norway Austria UK US Singapore Australia
There are some issues associated with exploring subjective experiences of epilepsy. One issue is the influence of culture on perceptions. For instance, Asadi-Pooya and Sperling (2007) compared epilepsy patients in Iran and the USA for their beliefs about the relationship between food and seizures. They found that only 5.7% of patients in the US reported a relationship, whereas 55.2% of patients from Iran believed that consumption of specific foods provoked the occurrences of seizures. Asadi-Pooya and Sperling raised a number of
4
Jaya Pinikahana and Joanne Dono
possibilities for the results, including differences in cultural beliefs, traditions or superstitions, or attention paid to diet and lifestyle. Another issue is that despite evidence of people experiencing warning signs, initial symptoms and precipitants of seizures, the extent that seizures are predictable (and thus controllable) is contentious. Millet et al., (2001) argued that most seizures occur randomly and anecdotal reports of associations between seizures and specific activities (e.g. cognitive exertion) arise from people wanting to attribute a cause to seizures. They failed to find an association between cognitive exertion (a commonly mentioned seizure precipitant) and increased risk of seizure, and concluded that people may be unnecessarily restricting their lifestyles and miss many opportunities for fear of having a seizure. Conversely, Rajna et al., (2008) put forward a medical hypothesis that for people with weak epileptic susceptibility, the appearance of an epileptic seizure needs a very strong precipitating/provoking event, which is best managed by eliminating the event rather than taking antiepileptic drugs. Indeed, Aird (1983) achieved good results by promoting moderate lifestyle changes, with results that were comparable to using most of the new antiepileptic drugs. However, Rajna et al. did concede that the subjective nature of precipitating events is difficult to prove scientifically, and that there is extreme inter-individual variability. There is a growing acceptance that what precedes the seizure can be as important as the seizure itself (Mula, 2007). Although the research is limited, a number of studies have reported evidence of self-developed techniques used by respondents to abort or avoid seizures. The percentage of participants reporting that they could avoid or abort seizures ranged from 20% to 52%, and included strategies such as keeping calm, concentrating hard, lying down, and relaxation techniques (see Cull et al., 1996; da Silva Sousa et al., 2005; Lee and No, 2005; Rajna et al., 1997). Spector et al., (2001) explored the concept of perceived self-control in relation to seizures and found that while there was no statistical relationship between warning signs and perceived self-control, all those who experienced at least one seizure precipitant had high levels of perceived control of seizures. However, earlier research by Cull et al. (1996) demonstrated that those who claim to inhibit their seizures represent 68% of those who report having warnings and 60% of those who are aware of seizure precipitants. Although much is known about clinical, neurological, psychiatric and even therapeutic aspects of epilepsy, very few studies of seizure precipitants, warning signs and self-control of seizures have been published in Australia or overseas. The identification of warning signs and initial symptoms of seizures, and of precipitating seizure factors may facilitate the development of specific counter measures that supplement existing epilepsy therapies and interventions. It is evident that without information that provides an accurate profile of warning signs, initial symptoms, and precipitants of seizures, any preventive strategies can not be properly formulated. Thus the development of pre-emptive intervention requires robust information based on patient self-report. It is also important to establish whether people who experience warning signs or have precipitant factors preceding their seizures feel that they have any self control over inhibiting or avoiding seizures and the strategies they may use. Subjective experiences may be more useful in assisting health professionals to devise treatment plans tailored to the individual, and therefore improvements in awareness and understanding could encourage people to learn how to recognise warning signs, initial symptoms and precipitant factors of their seizures. Understanding the processes associated with their seizures may lead a person with epilepsy to feel like they have some control over their condition.
Towards a Better Understanding of Living with Epilepsy
5
It was therefore the aim of this study to document the warning signs, initial symptoms and precipitating factors of epileptic seizures in a sample of people living with epilepsy. More specifically, the objectives were to examine the self-perception of warning signs, initial symptoms and precipitants of epileptic seizures in a sample of people with epilepsy; to investigate the perceived self-control of managing epileptic seizures and the techniques used; and to explore differences in demographic characteristics, living with epilepsy characteristics, and seizure types in relation to seizure prediction and self-control for people with epilepsy.
Method Participants were recruited from the Epilepsy Foundation of Victoria‘s social research participant register. A questionnaire, entitled the Seizure Prediction Tool (SPT), was constructed using different elements of the existing literature on the subjective experiences of epilepsy. The SPT contained both short-answer and multiple response questions and was designed to be a comprehensive assessment of subjective experiences leading up to a seizure, including awareness of warning signs, symptoms, and triggers of seizures, as well as any attempts to inhibit a seizure. Participants were also asked to provide details regarding demographics, living with epilepsy and seizure characteristics. Following ethics approval from Monash University‘s ethics committee, a package containing an introductory letter, a plain language statement, the SPT questionnaire and a reply paid envelope was sent to the people registered on the Epilepsy Foundation of Victoria social research database. The length of time estimated for completing the survey was 30 minutes. Data were collected for approximately 2 months following the initial mail out, and were then summarised and analysed using SPSS. Following the descriptive methods, the data were analysed for statistically significant associations between variables using chi-square tests (Fisher‘s exact tests when applicable), ttests, and Mann-Whitney U or Kruskal-Wallis tests for assessing mean rank differences in ordinal variables. A significance level of 0.05 was used to assess statistical significance.
Results General Characteristics of the Participants Participants provided information on the following demographic characteristics: epilepsy status, age, gender, educational level, employment status, marital status, living situation and living arrangements. A total of 225 of 338 people with epilepsy who had previously registered interest in participating in research completed a self-report questionnaire, giving a response rate of 66.6%. Participants were aged between 18 and 83 (mean = 47.6, SD = 14.7), and nearly two-thirds of the sample were female (64.9%). The most frequent categories for the remaining demographic characteristics were Caucasian (95.8%) for ethnic background, high school certificate (38.2%) for educational level, part-time (24.0%) for employment status, married (43.1%) for marital status, outright owner (34.2%) for living situation, and living with partner (43.6%) for living arrangements.
6
Jaya Pinikahana and Joanne Dono
Participants provided information regarding their experiences of living with epilepsy. The mean number of years they had had epilepsy was 24.9 (SD = 16.7), with a mean age at first seizure of 21.66 (SD = 17.4). Participants reported on the time taken to diagnose epilepsy following the first seizure, with time frames ranging from immediately to over 11 years. The most commonly reported length of time taken to diagnose epilepsy was between one month and one year (24.4%). A total of 47 people (20.9%) had undergone surgery to treat epilepsy. Participants provided information on the types of seizures they experienced, choosing as many as applicable from a list of 7 options: simple partial, complex partial, absence, tonic clonic, myoclonic, tonic and atonic seizures. More than half (58.2%) of participants reported experiencing tonic–clonic seizures. Absence, complex partial and simple partial seizures were reported by 35.6, 34.2, and 20% of participants, respectively. Only 8% reported other seizure types (e.g., myoclonic, atonic, and tonic), and 8.4% did not report any seizure type. The majority of participants experienced only one seizure type (51.1%), although 21.8% did report experiencing two seizure types, and 18.7% reported experiencing more than three seizure types. Of those who had experienced seizures in the past 12 months (56%), the majority reported 10 or fewer seizures per month (72.2%), although the frequency of seizures ranged from 1 in the past year to about 6480 (or about 540 per month).
Recognition of Initial Symptoms Participants were provided with a list of sixteen warning signs and initial symptoms of seizures and were asked whether they had experienced or noticed any of them prior to a seizure. The list included items such as funny feeling, anger, limb weakness and urge to defecate. One hundred and ninety-five (86.6%) of participants indicated that they experienced at least one symptom prior to a seizure. The most frequent symptom for the total sample was funny feeling (68.4%), followed by confusion (52.0%) and anxiety (45.8%). Males and females gave comparable responses across all symptoms, but there was a significant effect for age. Younger participants were more likely to report symptoms such as funny feeling, confusion, trembling, irritability, childish behaviour, anxiety, speech disturbance, headache, nausea, anger and limb weakness than older participants. Furthermore, people with epilepsy who stated that they experienced ‗no symptoms‘ prior to a seizure were older than those that experienced at least one symptom. A Kruskal-Wallis test was conducted to assess mean difference in number of symptoms given. The result was significant, with mean rank decreasing as age increased, indicating that younger groups reported higher number of symptoms than older groups, χ2(3, N = 220) = 19.28, P 1 AED divided by the number of days in the quarter) in 33,658 adults with epilepsy, found that patients who were non-adherent had a 3-fold increased risk of mortality after controlling for key epilepsy and demographic variables (R. E. Faught, Weiner, Guerin, Cunnington, and Duh, 2009). Similarly, studies examining sudden unexplained death in persons with epilepsy (SUDEP) suggest that patients had suboptimal AED serum levels at autopsy (Leestma, Walczak, Hughes, Kalelkar, and Teas, 1989; Lund, 1974; Neuspiel and Kuller, 1985). These studies provide preliminary evidence that the consequences of non-adherence can be fatal for individuals with epilepsy. Understanding adherence to AEDs is of paramount importance because stopping and starting AEDs may lead to pharmacoresistance and intractability (Perucca, 2001). For example, it is unclear whether patients who miss occasional doses of their AED develop pharmacoresistance compared to patients with complete non-adherence (i.e., 0%). Poor adherence also affects health care provider behavior, potentially leading to increased dosages, discontinuation of medication believed to be ineffective (DiMatteo, et al., 2002; DunbarJacob and Mortimer-Stephens, 2001), or AED polytherapy. Recent data suggest that 71% of pediatric patients who had an AED dosage increase demonstrated suboptimal adherence and that the dosage increase may have been ―avoidable‖ with the institution of adherence interventions (Koumoutsos, Modi, Morita, Monahan, and Glauser, 2007). Similarly, data from clinical trials evaluating new treatments and effective doses can also be compromised by poor adherence to the treatment (Christensen, 2004; Urquhart and Chevalley, 1988). Finally, estimates of the health care dollars wasted due to poor adherence range from 100 to 300 billion annually(Berg, et al., 1993; DiMatteo, 2004a). Based on the RANSOM study, non-adherence to AED therapy was associated with a higher incidence of emergency room visits, hospital admissions, motor vehicle injuries, and fractures (R. E. Faught, et al., 2009). Similar results were demonstrated in elderly patients with epilepsy, including increased inpatient, outpatient, and total health care costs for patients who were nonadherent versus adherent (Ettinger, Manjunath, Candrilli, and Davis, 2009). The financial impact of poorly controlled epilepsy is significant, with annual direct costs of approximately $5,000 a year per child with uncontrolled seizures compared to $1,900 for children whose seizures are wellcontrolled (Argumosa and Herranz, 2004). Applying a non-adherence prevalence rate of 24.8%, a conservative estimate, suggests that 188.3 million medical visits result in patients not following the advice they are given (DiMatteo, 2004a). In sum, poor adherence is cited as one of the major causes of treatment failure. TAKE HOME MESSAGE: AED non-adherence is associated with poor seizure control, increased risk of mortality, SUDEP, clinical-decision making, and unnecessary health care expenditures
Adherence to Antiepileptic Drug Therapy across the Developmental Life-Span 179 Table 1. Medication Adherence Measurement TYPE Objective Pill Counts/ Prescription Refills
STRENGTHS
Easy to collect in managed care setting Inexpensive
Electronic monitors
Continuous Long-term Real-time
Blood serum levels
Hair serum levels
Saliva concentration
Subjective Self-report
Provider Estimate Diary
Objective Quantifiable Sensitivity Clinical utility Objective Quantifiable Sensitivity Less invasive serum testing Objective Quantifiable Individual tailoring Painless (no venous access)
LIMITATIONS
Variable prescription sources or unknown source Does not account for samples Presumptive dosing Potential for medication discarding Expensive Technical problems Lost monitors Presumptive dosing Pharmacokinetic variation Short-term Invasive Debatable effectiveness Pharmacokinetic variation
26-50% (Ettinger, et al., 2009; E. Faught, et al., 2008; Manjunath, et al., 2009)
14% (Mitchell, et al., 2000; A. C. Modi, et al., 2008; Takaki, et al., 1985) 43% (Shope, 1988)
11-34% (Buelow & Smith, 2004; J. A. Cramer, et al., 1989; J.A. Cramer, et al., 1995) 40-41% (Kemp, et al., 2007; Mattson, et al., 1988)
12-35% (Al-Faris, et al., 2002; AsadiPooya, 2005; Asato, et al., 2009; Kanner, 2003; Kyngas, 2000a, 2000b; Mitchell, et al., 2000; Shope, 1988)
4-60% (Buck, et al., 1997; Doughty, et al., 2003; Gomes & Maia Filho, 1998; Gopinath, et al., 2000; Hovinga, et al., 2008; Jones, et al., 2006; Peterson, et al., 1982)
Debatable efficacy Pharmacokinetic variation Calibration to individual saliva production
Feasibility Patient perception Inexpensive Comprehensive Multiple informant
Social desirability Recall biases Developmental (young age) Global estimates
Inexpensive Feasibility Simple Strong ecological validity Comprehensive Real-time/shortrecall periods Minimize recall limitations
NON-ADHERENCE RATES Pediatrics Adults
Overestimates Poor accuracy Global estimates Poor adherence Time-intensive Expensive Scheduling for telephone diary Limited age range
180
Avani C. Modi and Shanna M. Guilfoyle
Adherence Measurement Given the strong association between non-adherence and morbidity, mortality, poor quality of life and higher healthcare costs, establishing reliable and valid measures of adherence is imperative. Adherence assessment has been studied extensively within other chronic illnesses (e.g., asthma, cystic fibrosis, diabetes); however, the measurement of adherence to AEDs has received minimal attention, with the exception of a recent critical review (Paschal, Hawley, St Romain, and Ablah, 2008). Techniques to assess adherence to AED therapy have evolved in the past thirty years, yet no clear ―gold standard‖ has been identified. Objective (e.g., electronic monitors) and subjective (e.g., self-report) measures of adherence have been utilized within epilepsy and account for significant variability in rates across the lifespan. For example, non-adherence rates to AED therapy range from 12 to 43% for pediatric populations and 4 to 60% for adult populations (See Table 1). Each method has strengths and weaknesses (see Table 1), which need to be considered by both researchers and clinicians when determining how to best assess a patient‘s adherence.
Objective Adherence Measurement The use of objective adherence assessment has received increasing attention in the past twenty years due to advances in pharmacology and technology. Several objective adherence measures exist, including pill counts, prescription refill, electronic monitoring, and bioassay/serum levels, which will be reviewed below. Pill Counts and Prescription Refill Methods. Non-adherence rates with AED therapy, as measured by pill counts and prescription refill methods, vary from 26-50% in the adult literature (Ettinger, et al., 2009; E. Faught, et al., 2008; Manjunath, et al., 2009), but have yet to be applied within pediatrics. Pill counts and prescription refills are often used to infer adherence by recording the quantity of medication that remains in a pill bottle or the number of refills that have been obtained since the prior clinic visit. Although these methods are noninvasive, they are severely limited due to 1) the necessity of having individuals remember to bring in their medication bottles to clinic visits, 2) difficulty accounting for samples that patients may have been given, and 3) the potential for human error/deception (e.g., pill dumping). AEDs are also often prescribed in liquid form for young children who have difficulty swallowing tablets. Although the ingestion vehicle (i.e., liquid versus pill) is not a barrier to using prescription refill methods, pill counts may not be a consistently viable adherence method for young children with epilepsy. Obtaining prescription refill history has similar limitations to pill counts, as well as lack of proper documentation in medical charts and the use of multiple pharmacies by families, including on-line pharmacies which have become more popular. Given that many AEDs need to be dosed within certain periods of time (i.e., every 12 hours), pill counts and prescription refills do not provide the level of detail necessary to ascertain dosing-specific adherence. This level of information may be critical to identifying the potential causes of break through seizures for patients with epilepsy. Electronic Monitoring Methods. Non-adherence rates with AED therapy, as measured by electronic monitoring methods, vary from 14-21% in pediatrics (Mitchell, et al., 2000; A. C. Modi, Morita, and Glauser, 2008; Takaki, et al., 1985) and 11-34% in adults (Buelow and
Adherence to Antiepileptic Drug Therapy across the Developmental Life-Span 181 Smith, 2004; J. A. Cramer, Mattson, Prevey, Scheyer, and Ouellette, 1989; J.A. Cramer, Vachon, Desforges, and Sussman, 1995). Recent technological advances have aided in the ability to automatically measure medication adherence by having computer chips embedded within medication vials (i.e. electronic monitoring). Specifically, a ―time-stamp‖ of precise medication dosing (i.e., tablet or liquid) is recorded and the date and time individuals open their medication vials is stored within the computer chip. Data can be stored for several months to a maximum of 3 years and is downloaded into data files based on the research/clinical needs. The Medication Event Management System (MEMS) caps are one example of electronic monitors used to examine AED adherence. The ability to capture adherence behaviors in ―real-time‖ over extended, continuous periods of time is a primary advantage of electronic monitoring compared to other adherence assessment techniques. Embedded within this strategy is the ability to detect more detailed information, such as: a) underdosing, b) overdosing, c) delayed dosing, d) dosing omissions over a brief period of time (i.e., drug holidays), and e) white-coat adherence (i.e., dumping medications or taking them consistently several days prior to clinic visits to improve adherence) (Quittner, Modi, Lemanek, Ievers-Landis, and Rapoff, 2008). Furthermore, electronic monitoring data provides a unique opportunity within epilepsy to examine the timing of dosing and whether specific ―dosing windows‖ are optimal to maximize seizure control.
Copyright Aardex Ltd. Figure 1. Patient Example of AED Adherence Data from the MEMS TrackCap.
182
Avani C. Modi and Shanna M. Guilfoyle
For example, Figure 1 shows detailed electronic monitoring information on when this patient took their AED doses (blue dots), missed doses (red triangles), and full days when no medication was taken (red lines). These data could be used to better assess the role of nonadherence on seizure control for individual patients. The precision of electronic monitoring in capturing medication dosing has been used as the criterion to determine the validity of other adherence measurement methods, such as selfreport and pill counts. Unfortunately, this technology captures presumptive medication dosing, as ingestion cannot be verified, and its clinical feasibility and utility is debatable at this time (e.g., cost, equipment malfunctioning, use of pill boxes). Although there continues to be debate about the best adherence measure, electronic monitoring appears to be the most innovative and precise measurement tool for AED therapy to date (J. A. Cramer, 1995; Rapoff, 1999) and likely represents the ―gold standard.‖ Biomedical Assay Methods. Biomedical assays provide quantitative data on the presence of medication in the body. Based on blood serum levels, the non-adherence rate for AED therapy is approximately 40% in adults (Kemp, et al., 2007; Mattson, Cramer, and Collins, 1988) and unknown in pediatric populations. Biomedical assays address a common concern of electronic monitoring, presumptive medication dosing, by confirming medication ingestion. AED levels in blood plasma or serum are the most commonly used biomedical assay to measure adherence. Ideally, patients provide blood plasma/serum levels when their level is a trough, defined as the point of minimum drug concentration. When serum levels are zero, patients who are on monotherapy can be assumed to be completely non-adherent to their AED for the few days prior to having their blood taken. However, decreased medication levels or subtherapeutic levels only indicate some degree of non-adherence but the level is unclear. Furthermore, determining non-adherence becomes more complex and challenging when an individual‘s treatment regimen involves more than one AED and when considering the multiple factors that determine AED serum levels. Specifically, pharmacokinetic variability involves the rate that a drug is absorbed, distributed, metabolized, and eliminated by the body (Perucca, 2002). Factors, such as demographics (e.g., body weight), pathophysiological (e.g., metabolic function), and therapeutic features (e.g., comorbid medications), can regularly alter dose-concentration relationships. For example, therapeutic doses often alter over time given the rapid growth and metabolic changes that occur during childhood, so a specific therapeutic dose may not remain therapeutic across developmental stages (e.g., transition from childhood to adolescence). Furthermore, biomedical assays only provide adherence information over a brief period of time (48-72 hours prior to assay obtainment). This is problematic when adherence rates over extended periods of time are of interest. Specifically, some evidence suggests that patients alter their adherence several days prior to clinic visits by engaging in white-coat adherence, defined as an increase in medication-taking prior to a clinic appointment or blood level assessment. Newer biological methods to assess adherence are also being tested. For example, AED levels detected from human hair (e.g., (Williams, et al., 2002)), either through gas chromatography mass spectrometry (e.g., (Goulle, et al., 1995)) or isocratic high-performance liquid chromatography assays (e.g., (Mei and Williams, 1997), and saliva concentrations (e.g., (Herkes and Eadie, 1990) have been more recently used additional biologic techniques to measure adherence. Although both human hair and saliva concentrations have been reported to have similar sensitivities to AED blood plasma levels, their effectiveness and clinical utility are debatable. Given that saliva concentration measurement is relatively
Adherence to Antiepileptic Drug Therapy across the Developmental Life-Span 183 painless, this may be a promising method for measuring AED levels for children (Baumann, Ryan, and Yelowitz, 2004), as many children experience procedure-related anxiety when receiving blood draws and this approach does not necessitate venous access. However at present, their utility in measuring AED adherence is limited and pharmacokinetic variability likely also impacts their validity in measuring adherence.
Subjective Adherence Measurement Subjective methods of adherence measurement (e.g., surveys, questionnaires, interviews) are typically provided by patients and/or their caregivers and are commonly used by clinicians and researchers. While self-report methods are easy to obtain within clinic settings, significant discrepancies across subjective methods can exist due the depth and variability of these techniques. Several factors contribute to these discrepancies, including respondent (e.g., youth versus caregiver versus adult), setting (i.e., inpatient versus outpatient), assessment time frame and the psychometric properties associated with each measurement method. Although subjective adherence methods are based an individual‘s perception of their adherence and have practical utility (i.e., cost-efficient, comprehensive, practical), which contributes to their popularity, they are vulnerable to reporting biases (Rand, 2000). Subjective methods are also notorious for overestimating adherence behaviors when compared to objective methods and may represent global perceptions of adherence (e.g., ―Are often do you take your valproate?‖) versus quantitative measurement (e.g., ―How many doses of medication have you missed within the past week?‖). Self-Report Methods. AED non-adherence, as determined by self-report methods, vary from 12-43% in pediatrics (Al-Faris, Abdulghani, Mahdi, Salih, and Al-Kordi, 2002; AsadiPooya, 2005; Asato, et al., 2009; Kyngas, 2000a, 2000b; Mitchell, et al., 2000; Shope, 1988) and 4-60% in adults (Buck, et al., 1997; Doughty, Baker, Jacoby, and Lavaud, 2003; Gomes and Maia Filho, 1998; Gopinath, et al., 2000; Hovinga, et al., 2008; Jones, et al., 2006; Peterson, et al., 1982). Within epilepsy, there are no validated, disease-specific self-reported AED adherence measures. More commonly, and particularly within the adult population, AED adherence has been assessed using both structured and unstructured surveys and interviews, often by asking brief qualitative questions about medication taking behaviors (see (Paschal, et al., 2008) for a review). Qualitative questions aid in ascertaining the contextual and behavioral factors that may influence adherence. For example, Buelow and Smith (2004) developed a semistructured interview to establish a patient‘s perceived ability to manage their medications (Buelow and Smith, 2004). Embedded within this assessment are questions that more specifically probe about an individual‘s medication regimen (e.g., ―Tell me if you are able to follow their instructions and how difficult or easy it is to follow the instructions.‖) and strategies to overcome adherence barriers (e.g., ―Tell me strategies that you use to remember to take your medications‖). The Morisky scale has also been used with adults with epilepsy and includes questions about how often patients forget to take their medication (Morisky, Green, and Levine, 1986). Structured interviews also provide the opportunity to further explore an individual‘s responses with additional questioning (Quittner, et al., 2008). This qualitative approach is particularly useful when working with adolescents and adults, but may be less useful for younger children.
184
Avani C. Modi and Shanna M. Guilfoyle
Within pediatric epilepsy, as with other chronic conditions, caregivers are often asked to provide adherence information, given that they are typically responsible for medication management for toddler and school-aged children. While self-report techniques have limited validity for children under the age of 8 years (Quittner, et al., 2008), young children may often provide unique information regarding AED adherence that is critical for intervention. For example, children may cheek or hide their medications because of side effects or bad taste, which would only be known by asking children themselves. As school-aged children transition to adolescence, a combination of both parent-proxy and self-report is encouraged. This is particularly true given that adolescence is generally associated with a critical decline in adherence due to a shift in responsibility that commonly occurs, including decreased parental supervision (A.C. Modi, Marciel, Slater, Drotar, and Quittner, 2008). Future research needs to focus on the development and validation of adherence self-report questionnaires for children, caregivers, and adolescents. For example, Modi and colleagues recently developed and validated a Pediatric Epilepsy Self-Management Questionnaire that contains an Adherence to Medication scale. This scale holds promise because it demonstrated construct validity with electronic monitoring and a single item ad-hoc adherence question (rs = 0.220.35, p < .05; (A. C. Modi, et al., 2009). Provider Estimate Methods. Health care providers, such as physicians and nurses, have also been asked to estimate their patient‘s adherence to AED therapy. Generally, provider estimates include global ratings that are dichotomized to classify patients as either ―adherent‖ or ―nonadherent.‖ Although the clinical/research utility of provider estimates is appealing (i.e., inexpensive, simple), their accuracy in detecting non-adherence is questionable (Finney, Hook, Friman, Rapoff, and Christophersen, 1993) and represents an overestimation of patient adherence (Wang and Haynes, 1988). Health care providers may also be biased by their general perceptions of the family when estimating adherence (e.g., family chaos may implicate poorer adherence). Diary Methods. Another subjective measure of adherence that has received little attention in epilepsy is diary methods, which usually involve tracking and reporting daily activities, including when medication is taken. Although this method is similar to self-report, it can be more unobtrusive and indirect. Traditionally, individuals have generated written logs of their activities (e.g., when they take their medications), but more modern technological advances allow this data to be obtained through hand-held computers (i.e., PDAs) and telephone diaries (Freund, Johnson, Silverstein, and Malone, 1991; Quittner and DiGirolamo, 1998). Specifically, ecological momentary assessment (EMA; (Csikszentmihalyi and Larson, 1987)) and day construction methods (DRM; (Kahneman, Krueger, Schkade, Schwarz, and Stone, 2004)) address primary limitations of questionnaire/interview measurement: memory, recall, and social desirability (Johnson, 1995; A. C. Modi and Quittner, 2006b; Quittner, Espelage, Ievers-Landis, and Drotar, 2000). These strategies allow individuals to provide data ―in the moment‖ or within a short, recall period (i.e., 24 hours) so that the specific frequency of behaviors (quantitatively) can be assessed rather than global perceptions (qualitatively). These data more closely converge with objective data compared to self-report methods of adherence (A. C. Modi and Quittner, 2006b) and lends itself to examining temporal ordering of behaviors to identify barriers to adherence. This process-level information offers researchers the ability to develop adherence interventions by examining barriers within the context of an individual‘s daily life (e.g., sports activity disrupting routine and medication was subsequently forgotten). Individuals are likely to be more truthful in their reporting when
Adherence to Antiepileptic Drug Therapy across the Developmental Life-Span 185 using daily diary methods because all daily activities are elicited (i.e., not just medication taking behaviors) and those participating in research are often unaware that adherence behaviors are a focus of interest (e.g., (A. C. Modi and Quittner, 2006b; Wiener, Riekert, Ryder, and Wood, 2004). On the other hand, daily diary methods are time-intensive, resource laden (e.g., training in use of technologies, time necessary for data collection), and are not designed for use with younger children. Two diary methods have been utilized within pediatrics to measure adherence: 24 hour recall (Johnson, Silverstein, Rosenbloom, Carter, and Cunningham, 1986) and the Daily Phone Diary (DPD; (Quittner and Opipari, 1994). Both measures have been classified as ―well-established‖ measures in a recent review of pediatric empirically supported assessments of adherence (Quittner, et al., 2008). Although diaries have been used with adult patients to track seizure activity, no studies have utilized diaries to assess adult and pediatric AED adherence. Taken together, each adherence measurement technique has the potential to provide unique, additive value in understanding how individuals with epilepsy manage their medications. As such, multi-method assessment that includes both objective and subjective indices of adherence are optimal when assessing AED adherence because results vary based on the measurement approach used (Mitchell, et al., 2000; A.C. Modi, S. M. Guilfoyle, et al., 2008). The future of adherence measurement studies is wide open for both pediatric and adult populations and there is a significant need to determine a viable tool for both clinical and research purposes. If self-report is the easiest and most clinically-useful tool to assess adherence, one potential way to reduce inflated results is to identify a ―correction factor‖ based on comparisons with a more objective measure (Jasti, Siega-Riz, Cogswell, and Hartzema, 2006). In contrast, if electronic monitors become more cost-efficient, they can be used in both clinical practice and for research purposes given their strong reliability and validity relative to other methods. Another important future direction in AED adherence measurement is the application of pharmacokinetic models to identify optimal AED serum levels based on the patient-specific factors (e.g., age, metabolism, weight) instead of using isolated serum levels to identify non-adherence. This type of therapeutic drug monitoring would be beneficial for patients because it would allow clinicians to provide treatment targeted at achieving a specific therapeutic level associated with the best seizure control and least side effects. TAKE HOME MESSAGE: Electronic monitoring of AED adherence provides the most accurate portrait of adherence and should be used within clinical settings, if possible Self-report methods are inexpensive but provide inflated reports of adherence; however, the development of more reliable and valid self-report measures is an important next step
Predictors of AED Adherence Understanding factors that contribute to poor adherence is a critical first step in identifying targets for adherence interventions. To date, several sociodemographic, medical,
186
Avani C. Modi and Shanna M. Guilfoyle
individual and familial, and healthcare-specific factors have been linked to AED adherence, which are represented in Figure 2.
Sociodemographic Factors Within the epilepsy adherence literature, associations between sociodemographic factors and adherence have been studied extensively. However, results of these studies vary based on how adherence is measured and the developmental period assessed. For example, age does not appear to be correlated with adherence in pediatric populations (Al-Faris, et al., 2002; Asadi-Pooya, 2005; A. C. Modi, et al., 2008; Takaki, et al., 1985), but findings are mixed for adults with epilepsy (Buck, et al., 1997; J. A. Cramer, et al., 1989; Dodrill, Batzel, Wilensky, and Yerby, 1987; Friedman, et al., 1986). Buck and colleagues (1997) reported higher selfreported adherence for patients over 60 years of age (86%) compared to those under 60 years of age (66%), and for patients over 20 years (72%) compared to adolescents (52%). In contrast, age was not correlated with saliva levels (Friedman, et al., 1986) or serum levels (Dodrill, et al., 1987) in adults. Although age appears to be unrelated to adherence, no studies have assessed the relations across the lifespan. However, it is likely that adherence declines during adolescence, a developmental period that is marked by a drive for independence and autonomy, which has been found in the broader adherence literature (Anderson, Ho, Brackett, Finkelstein, and Laffel, 1997; Mellins, Brackis-Cott, Dolezal, and Abrams, 2004; Zindani, Streetman, Streetman, and Nasr, 2006).
Figure 2. Comprehensive Model Depicting Predictors of AED Adherence.
Adherence to Antiepileptic Drug Therapy across the Developmental Life-Span 187 Other sociodemographic factors have also been examined in relation to adherence, including sex, education, and socioeconomic status (SES) (Al-Faris, et al., 2002; AsadiPooya, 2005; Buck, et al., 1997; J. A. Cramer, et al., 1989; Dodrill, et al., 1987; Friedman, et al., 1986; Gomes and Maia Filho, 1998; A. C. Modi, et al., 2008; Snodgrass and Parks, 2000). For children and adolescents specifically, parental education, family composition, pubertal status, and parental marital status have also been assessed. Overall, data suggest no significant relations between adherence and sex or pubertal status. A single study has demonstrated that higher maternal age, positive family history for epilepsy, and large family size were correlated with poor adherence for children in Iran (Asadi-Pooya, 2005). These findings have yet to be cross-culturally replicated. The strongest finding in the epilepsy adherence literature is in relation to SES. Specifically, lower SES was associated with poor adherence for pediatric patients as measured by MEMS Trackcaps (A. C. Modi, et al., 2008) and serum levels (Snodgrass, Vedanarayanan, Parker, and Parks, 2001). Modi and colleagues (2008) also demonstrated that children of non-married parents exhibited lower adherence rates than children of married parents. Similarly, one adult study found that adults exhibiting AED nonadherence were more likely to have lower education and perceive themselves to be in financial distress (Dodrill, et al., 1987). Combined, these data indicate that lower SES and education negatively affects adherence to AED treatment. This is likely due to the competing demands and limited resources that families and patients experience. For example, an adult of lower SES and education may have financial strains that limit his/her ability to access AEDs or understand the importance of medication adherence. In turn, he/she may neglect to consistently take AEDs. Although sociodemographic factors are less amenable for modification, they are critical to consider when optimizing adherence.
Medical Predictors Although AED non-adherence has been consistently identified as a predictor of poor seizure control, epilepsy-specific factors that contribute to AED non-adherence are not well understood. Seizure and AED treatment characteristics, along with disease duration, have been the primary foci of research with inconsistent results across pediatric and adult epilepsy populations. Epilepsy Type. Patients with epilepsy can manifest several different seizure types; however, most patients are classified as having partial, generalized or unclassified epilepsy types. The type of epilepsy has not been consistently identified as a predictor of AED adherence (Buck, et al., 1997), particularly when objective methodology is utilized (A. C. Modi, et al., 2008; Takaki, et al., 1985). However, some studies suggest an association with generalized tonic-clonic seizures and self-reported AED adherence in both children and adults (Al-Faris, et al., 2002; Peterson, et al., 1982). That is, patients with tonic-clonic seizures tend to report better adherence on self-report questionnaires. Several explanations could account for this finding. The intensity and severity of tonic-clonic seizures may lead patients to perceive that they are more adherent, despite objective adherence findings. Conversely, individuals who have experienced tonic-clonic seizures, which are often unpleasant, anxietyprovoking, and potentially embarrassing, may be more motivated to adhere to their medication regimen.
188
Avani C. Modi and Shanna M. Guilfoyle
AED Dosing Frequency. Several studies have examined the role of AED dosing on adherence, which will increase as more sustained-release formulations come into the market. For example, a sustained-release formulation of valproate, which is commonly used to treat tonic-clonic seizures and requires only once daily dosing, has been used as an alternative option to VPA immediate-release, which requires twice daily dosing. To support this notion, Doughty and colleagues (2003) conducted an observational study of adults with epilepsy across eight European countries. Results identified that self-reported adherence improved when medication dosing frequency decreased from twice daily (e.g., VPA immediate-release) to once daily dosing (e.g., VPA sustained-release) (Doughty, et al., 2003). More importantly, this decrease in dosing frequency resulted in better seizure control. The association between dosing frequency and AED adherence was more rigorously tested by assessing adherence through the use of MEMS caps. In a seminal study, Cramer and colleagues (1989) explored adherence in both newly diagnosed and long-term adult patients with epilepsy. Results indicated that AED adherence systematically decreased as the frequency of medication dosing increased, with adherence rates averaging 87% for once daily dosing to 39% for four times daily dosing (J. A. Cramer, et al., 1989). These results were replicated in a controlled clinical trial using MEMS technology to assess adherence to vigabatrin (VGB) compared to standard AED treatment, for adults with complex partial epilepsy with poor seizure control (J.A. Cramer, et al., 1995). Monotherapy versus Polytherapy. Cramer and colleagues (1995) also compared adherence for adults using polytherapy, which is common for individuals with poor seizure control, to those on monotherapy. Findings indicated that polytherapy did not significantly predict VGB adherence (J.A. Cramer, et al., 1995). Yet in a study conducted two years later, polytherapy was significantly associated with AED self-reported non-adherence (Buck, et al., 1997). Authors speculated that patients following a polytherapy AED regimen likely have a history of higher seizure activity, which may lead them to feel more motivated to follow their treatment regimen. The association between the number of medications prescribed and AED adherence has not been supported in a pediatric sample (Asadi-Pooya, 2005). Overall, these data suggest that polytherapy may have an impact on self-reported adherence compared to when AED adherence is measured objectively. AED Side Effects. Medication side effects, which can affect physiology, cognition, emotion, and behavior, can detrimentally affect a patient‘s willingness to consistently follow their treatment regimen. However, poor medication adherence can also be caused by some of these same side effects. Although medication side effects have been linked to AED nonadherence in both pediatric (Al-Faris, et al., 2002) and adult (Eiser, 1993; Eisler and Mattson, 1975) samples, the reciprocal nature makes it difficult to know the direction of these findings. One notion suggests that the nature of the side effects, which often have deleterious effects on the central nervous system, are more obtrusive on psychosocial functioning and lead patients to stop taking their medications. On the other hand, patient motivation to consistently adhere to their medication regimen may be lowered by the frequency or intensity of the AED side effects, which may compromise quality of life and subsequent medication adherence. Further research is necessary to determine which side effects are considered tolerable and which have such adverse side effects that they compromise adherence and possible seizure control. Disease Duration. For most chronic conditions, such as diabetes and asthma, patients are expected to take medications for the long-term. In contrast, patients with epilepsy who are seizure-free for two years have the potential to wean from AED treatment, which can elicit
Adherence to Antiepileptic Drug Therapy across the Developmental Life-Span 189 hope for patients. However, 30% of patients with epilepsy will develop pharmacoresistance or intractability. The burden and stress of managing epilepsy and taking AEDs long-term may have an impact on adherence. In a sample of 95 children and young adults prescribed phenobarbital with poor seizure control, Takaki and colleagues (1985) found that the percentage of adherent patients, as determined by plasma levels, was significantly higher in patients taking AEDs for at least 5 years compared to those taking AEDs for 0-4 years (Takaki, et al., 1985). However, duration of epilepsy was not a significant predictor of adherence in a community-based sample of adults based on self-report (Buck, et al., 1997) or within a pediatric sample utilizing more objective methods (Asadi-Pooya, 2005). Findings within the pediatric sample may be attributable to the young age of the sample and the brief period of time since seizure onset (i.e., less than two years). However, support for the association between disease duration and AED adherence detected within adult studies may have important implications for the adherence challenges faced by adults with intractable epilepsy. This may be particularly critical given that adults defined as ―nonadherent‖ to their AED within one year of medication initiation were found to be at a 21% higher risk for seizure activity compared to adults labeled ―adherent‖ (Manjunath, et al., 2009).
Individual and Family Predictors of Adherence Beyond socio-demographic and medical predictors of adherence for patients with epilepsy, there are multiple individual and family factors that have been shown to contribute to poor adherence. Individual factors include intellectual functioning, knowledge about the disease and its treatments, health/illness beliefs, perceived treatment efficacy, locus of control, psychopathology, and barriers and facilitators of AED adherence. Family factors include constructs such as family cohesion, organization, caregiver illness/treatment beliefs, and caregiver psychopathology. Cognitive Functioning. Only two studies have investigated the relation between intellectual functioning and AED adherence. One pediatric study detected higher blood serum level adherence in patients with higher intellectual functioning (Mitchell, et al., 2000), but this was not replicated in an adult sample (J. A. Cramer, et al., 1989). While it is likely that higher cognitive functioning is required to establish a foundation for good disease management, more research needs to be conducted to determine the skills necessary to maintain adequate AED adherence for a neurological condition such as epilepsy. Lack of Knowledge. Although the relationship between adherence and both disease and treatment-related knowledge remains equivocal in the larger adherence literature, researchers have concluded that disease-related knowledge is necessary but not sufficient to improve adherence to medical regimens (La Greca, Follansbee, and Sklyar, 1990; McQuaid, Kopel, Klein, and Fritz, 2003; A. C. Modi and Quittner, 2006a; Tebbi, et al., 1986). Within pediatric epilepsy, caregivers have reported needing more information about their child‘s disease (Shore, et al., 1998) and lacking knowledge about epilepsy. In fact, data suggest that only 29% of parents of children with epilepsy knew the name or dose of their child‘s current medication and 22% of parents believed that swimming should be prohibited even when seizures were well-controlled (Kwong, Wong, and So, 2000). Preliminary evidence suggests that increasing knowledge of epilepsy and its treatments may be associated with initial
190
Avani C. Modi and Shanna M. Guilfoyle
improvements in adherence (Dawson and Jamieson, 1971; Helgeson, Mittan, Tan, and Chayasirisobhon, 1990). Parallel evidence regarding deficits in disease and treatment knowledge has been found in the adult epilepsy population. For example, Gopinath and colleagues (2000) reported that approximately 39% of adults were unaware of the potential for AED side effects. Similarly, 86% of adults acknowledged awareness of avoiding AED dose manipulations; however, onethird of patients did not believe there was any harm in missing one AED dose when seizures were well-controlled (Gopinath, et al., 2000). Although it is clear that both pediatric and adult epilepsy populations may lack disease and treatment-knowledge, it is surprising that selfreported and objective (e.g., saliva levels) AED adherence were not significantly correlated with knowledge (Friedman, et al., 1986; Gomes and Maia Filho, 1998). Health/Illness Beliefs and Perceptions. Individuals managing epilepsy have beliefs and/or perceptions about their disease and treatments that may impact AED adherence. Two adult studies demonstrated that adherence improves when AED therapy is perceived to be beneficial (Eisler and Mattson, 1975; Stanaway, Lambie, and Johnson, 1985). In contrast, denial of the illness and personal views about treatment efficacy may compromise selfreported AED adherence in children (Al-Faris, et al., 2002; Asadi-Pooya, 2005). The perceived importance of AED therapy and the stigma associated with an epilepsy diagnosis also influence self-reported adherence behaviors. Specifically, adolescent and adult patients with epilepsy who believed taking AEDs was ―very important‖ were found to report higher adherence rates compared to those who felt it was ―fairly/not at all important‖ to take AEDs as prescribed (79% versus 29% adherence; (Buck, et al., 1997)). Furthermore, stigma associated with an epilepsy diagnosis has been found to be related to non-adherence in adults (Buck, et al., 1997). Although these findings have not been replicated with objective adherence measures (Kemp, et al., 2007), the data provide insight into the health-related beliefs that influence self-reported AED adherence. If patients view AED therapy as beneficial, important and non-stigmatizing, they are more likely to report higher adherence. Compared to other epilepsy treatment recommendations, such as refraining from alcohol use and maintaining adequate stress management and sleep hygiene, adults with epilepsy seem to feel more capable of managing their AED therapy (Kobau and DiIorio, 2003). Interestingly, adult patients with epilepsy who perceive themselves to be following the advice of their healthcare team and taking medications as prescribed may demonstrate a mismatch with their actual adherence behaviors. Specifically, Buelow and Smith (2004) demonstrated that objective MEMS adherence data was inconsistent with patient-reported beliefs about their own medication management. Of the 14 patients who reported no AED adherence concerns, 71% demonstrated suboptimal adherence rates (Buelow and Smith, 2004). Kemp and colleagues (2007) found that neither illness representation, defined as how patients view and make sense of their illness, nor illness beliefs were associated with objective serum level adherence for adults with epilepsy (Kemp, et al., 2007). Overall, illness/health beliefs and perceptions appear to influence how individuals perceive their adherence behaviors, demonstrating potential bias in reporting. However, health-related beliefs specific to epilepsy have not been linked to objective AED adherence. Internalizing/Externalizing Behaviors. Children and adults with epilepsy are at increased risk for internalizing disorders (e.g., depression, anxiety) compared to healthy controls (Kanner, 2003; Rodenburg, Stams, Meijer, Aldenkamp, and Dekovic, 2005; Vazquez and Devinsky, 2003) whereas externalizing (e.g., hyperactivity, oppositional behaviors) disorders
Adherence to Antiepileptic Drug Therapy across the Developmental Life-Span 191 appear to largely affect the pediatric epilepsy population. Given the high prevalence of these disorders within epilepsy, there is a need to examine psychological factors contributing to poor adherence. The small literature examining the association between internalizing symptoms and AED adherence suggests no significant relation between these constructs (Dodrill, et al., 1987; Otero and Hodes, 2000). A single adult study indicated that worries about one‘s health may lead to higher self-reported adherence rates but this may be the indirect result of continued seizure activity contributing to elevated worries (Peterson, et al., 1982). A larger number of studies have examined the impact of externalizing symptoms in children on AED adherence. Behavior problems (e.g., inattention, lack of behavioral control) in children with epilepsy have been found to compromise adherence (Mitchell, et al., 2000). Similarly, Otero and colleagues (2000) found that children in the ―poor compliance‖ group had higher self-reported antisocial behaviors and parent-reported behavior problems. It is noteworthy that while oppositional and inattentive behaviors may serve as barriers to adherence, they may also be the result of AED side-effects, which are common (Besag, 2001, 2004). Family Predictors. Given the vulnerability of both pediatric and elderly populations, families and caregivers play a critical role around epilepsy management. For younger children and the elderly, the primary responsibility of ensuring that patients take their medication falls on the primary caregiver (e.g. parent, spouse); however, during adolescence, transition of responsibility from caregiver to the adolescent him/herself around disease management occurs. As the adolescent enters adulthood, the patient takes on sole responsibility for AED adherence. In pediatric epilepsy, lack of family harmony, lack of support, parental worry, and maternal hostility and criticism have been identified as family predictors of poor adherence (Hazzard, Hutchinson, and Krawiecki, 1990; Kyngas, 2000b; Mitchell, et al., 2000; Otero and Hodes, 2000). Given that adolescents are striving for increased autonomy and are developing a greater sense of self, caregiver-adolescent conflict may develop around epilepsy management. In fact, Friedman and colleagues (1986) identified that caregivers who excessively restrict the personal freedom of their adolescents compromise AED adherence, while those who foster a sense of autonomy in their adolescents promote better AED adherence (Friedman, et al., 1986). However, this data is not to negate that parental supervision is a necessary component for optimal AED adherence. Rates of self-reported adherence are high (87-88% versus 55-60%) when caregivers are primarily responsible for AED adherence (Asato, et al., 2009). Although research investigating the factors contributing to poor adherence among the elderly is only emerging (Ettinger, et al., 2009), family/caregiver variables for adults with epilepsy likely remain an area of future investigation. For example, many elderly adults have difficulty relinquishing typical disease management responsibilities that have been independently managed for many years.
Barriers and Facilitators of Adherence Researchers have attempted to elucidate patient-identified barriers and facilitators that may not neatly fit classifications outlined above. These patient-reported barriers provide critical data on potential targets for intervention to improve adherence.
192
Avani C. Modi and Shanna M. Guilfoyle Table 2. Medication Adherence Barriers and Strategies to Facilitate Adherence
Common Barriers
Pediatrics
Adults
Forgetting (Asato, et al., 2009) Side effects (Al-Faris, et al., 2002; Asato, et al., 2009)
Forgetting (Eisler & Mattson, 1975; Stanaway, et al., 1985) Side effects (Eisler & Mattson, 1975)
Asymptomatic (Asato, et al., 2009) Medication unavailable (Asato, et al., 2009)
Misunderstanding instructions (Stanaway, et al., 1985) Changing/stopping doses (Eisler & Mattson, 1975; Stanaway, et al., 1985) Fear of addiction (Eisler & Mattson, 1975; Gomes & Maia Filho, 1998) Denial of illness (Eisler & Mattson, 1975) Loss of medication efficacy ((Eisler & Mattson, 1975) & Mattson, 1975)
Unique Barriers
Adherence Facilitators Reminders (Asato, et al., 2009) Fitting medications into daily schedule (Asato, et al., 2009) Pill boxes (Asato, et al., 2009)
Barriers that are similar across pediatric and adult epilepsy include forgetting and medication side effects (See Table 2). However, unique developmental barriers have also been identified. For example, one unique barrier for adults with epilepsy is fear of medication addiction (Eisler and Mattson, 1975; Gomes and Maia Filho, 1998), which may need to be proactively addressed by health care providers prior to initiating AED therapy. One study has also identified facilitators of adherence within pediatric epilepsy (Asato, et al., 2009). These parent-identified strategies (i.e., facilitators) may be beneficial in overcoming adherence-related barriers, particularly when these strategies are shared amongst caregivers.
Healthcare Predictors of Adherence Beyond the individual, family, and disease/treatment factors that impact upon adherence, a few studies have examined the role of healthcare professionals, clinic appointments, and the
Adherence to Antiepileptic Drug Therapy across the Developmental Life-Span 193 system itself on adherence. Similar to adherence studies in other chronic illness populations, AED adherence is positively related to the number of clinic visits (Gopinath, et al., 2000) suggesting that closer follow-up facilitates better adherence. Given that attendance to clinic visits is often a precursor to AED adherence (Al-Faris, et al., 2002), it is not surprising that the visit itself may have some implications for adherence. The timing of clinic visits and its association with white-coat adherence has received some attention. Cramer and colleagues (1990) found that adherence within a sample of adults with epilepsy was significantly higher 5 days prior to and after a clinic visit (J. A. Cramer, Scheyer, and Mattson, 1990). However, white-coat adherence support was not detected in a sample of children newly diagnosed with epilepsy (A. C. Modi, et al., 2008). Sampling of adherence during different times of disease progress and development may account for such findings. For example, caregivers remain integral in seizure management for children, particularly shortly following diagnosis, which may minimize the likelihood of white-coat adherence occurring within pediatrics. Furthermore, some studies have suggested that a positive patient-provider relationship and patient satisfaction with their medical care can promote more optimal adherence. For example, Hazzard and colleagues (1990) found that higher adherence, as rated by physicians, was associated with greater satisfaction with medical care for caregivers of children with epilepsy. Similarly, Al-Faris (2002) reported that non-adherence was related to parental dissatisfaction with their child‘s clinical care (Al-Faris, et al., 2002). Within the adult population, effective physician-patient communication was correlated with higher adherence (Gopinath, et al., 2000). Although few studies have been conducted in this area, there is some evidence that satisfaction with medical care and a positive relationship with healthcare providers can promote adherence to AED therapy (Buck, et al., 1997). Future studies should further examine the role of providers, access to healthcare, and frequency of clinic visits on adherence in children, adolescents, and adults with epilepsy. TAKE HOME MESSAGE: Key and consistent factors associated with AED non-adherence include lower socioeconomic status, lower AED dosing frequency, negative beliefs about epilepsy and its treatments, child behavior problems, poorer family functioning, and adherence barriers, negative relationships with the healthcare team
Adherence Interventions Despite over 25 years of research dedicated to understanding medication adherence and predictors of non-adherence in pediatric and adult epilepsy populations, there are virtually no studies focused on interventions to improve adherence in epilepsy. Peterson and colleagues (1984) conducted one of the only randomized controlled clinical trials testing the effectiveness of a multi-faceted adherence intervention for adults involving counseling, psychoeducation, self-monitoring, mailed reminders for clinic appointments, and follow-up for missed medication refills (Peterson, McLean, and Millingen, 1984). Trial results suggested improvements for medication adherence and serum drug levels. At present, interventions targeting adherence among children and adolescents with epilepsy have yet to
194
Avani C. Modi and Shanna M. Guilfoyle
be developed or conducted; thus, we will discuss adherence interventions from other chronic diseases that may be applicable to epilepsy and should be empirically tested in the future. Adherence interventions developed within other chronic conditions range from simple treatments that are primarily psychoeducational to more complex, multifaceted interventions, as evidenced by Peterson and colleagues (1984). Three of the primary intervention approaches targeting medication adherence include educational, organizational, and behavioral strategies (La Greca and Schuman, 1995; Lemanek, 1990)see Table 3). However, one of the most challenging aspects of addressing adherence is simply initiating a discussion about adherence barriers and strategies to facilitate adherence. Often this topic is unacknowledged or intentionally avoided by both providers and patients. Strategies that are often helpful to initiate discussion about adherence include normalizing and not criticizing families for adherence difficulties and being very specific about how they fit medications into their daily routine (e.g. when they take it, last missed dose, barriers they experienced). Table 3. Adherence Interventions Interventions Education
Intervention Components Psychoeducation Verbal and written instructions
Organizational
Behavioral
Multi-Component
Regimen and daily schedule modifications Self-monitoring Problem-solving Chaining Contingency management Integration of education, organizational, and behavioral Social support Social skills training Family therapy
Helpful Strategies Conduct observations Instruction repetition Prioritizing skills Simple, easy to read handouts CD-ROMS/videos Simplifying regimens Dose timing adjustments Daily adherence logs Visual reminders (e.g., calendars, charts) Behavioral contracting Positive reinforcement Any of the above strategies
Adherence to Antiepileptic Drug Therapy across the Developmental Life-Span 195
Figure 3. AED Titration Schedule.
Educational strategies include health care providers offering factual information regarding the nature of the illness and its management, explaining the importance of following medication regimens, and providing guidance about the potential negative side effects of prescribed recommendations. Psychoeducation on the prescribed regimen, including anticipatory guidance about AED side effects, is critical because it can potentially compromise adherence. For example, some AEDS taken on an empty stomach can lead to stomach irritation and nausea. Discussion of this side effect and encouragement for patients to eat prior to medication dosing may prevent this side effect, thereby increasing AED adherence. Furthermore, periodic review of an individual‘s AED treatment regimen through the course of treatment can be beneficial, particularly when modifications to the regimen occur. For instance, when a new AED is initiated, a plan for titrating the medication is often reviewed with the patient. This strategy is particularly helpful to patients if reviewed both in written and verbal format and a copy is provided to the patient to take home (see Figure 3).
196
Avani C. Modi and Shanna M. Guilfoyle
Organizational strategies focus on the modification of regimen characteristics to promote better adherence. A common organizational intervention involves the simplification of a medication regimen. For example, if a patient with epilepsy is having difficulty following a medication regimen that involves twice daily dosing, an epileptologist may be able to simplify the regimen to once daily dosing if sustained-release formulations are available for a particular drug. However, when regimen simplification or schedule adjustments are not feasible, other strategies can be used. Brown and colleagues (2009) conducted a randomized clinical trial testing whether a simple, self-administered worksheet that asked adult patients to outline ―if-then‖ goal-based statements to improve AED adherence (e.g., ―If it is time X in place Y and I am doing Z, then I will take my pill dose‖). Results suggested that, compared to the control group, those in the intervention group demonstrated improved AED adherence (Brown, Sheeran, and Reuber, 2009). This intervention illustrates how a brief, easily administered self-report worksheet can be effective in increasing adherence behaviors. Finally, patients have anecdotally reported that use of pillboxes can be beneficial when placed in a convenient location, such as the bathroom or kitchen table. Behavioral approaches designed to optimize medication adherence often involve conducting a functional behavioral assessment (Carr, et al., 2000) of the adherence barrier and developing a specific plan to address the barrier. Basic behavioral approaches can include incorporating visual reminders (e.g., calendars, charts) or self-monitoring (e.g., tracking medication dosing through a daily log) to overcome forgetting. Chaining of behaviors, which is associating new behaviors with established behaviors (i.e., daily routines), is also a helpful strategy to promote adherence. For example, patients often benefit from chaining medication dosing to activities, such as eating breakfast or brushing their teeth. Contingency management strategies, which utilize basic behavioral principles, are helpful to motivate behavior change in young children. Specifically, caregivers can use charts or calendars to encourage behaviors that promote better AED adherence. By using behavioral charts/calendars, youth or their caregivers can mark off the days the AED was taken on a calendar or chart with the goal of working towards a reward, such as movie tickets. As mentioned, these more intensive interventions often include caregivers to implement necessary behavior change to optimize adherence. Supervision (i.e., monitoring) by caregivers is often necessary to facilitate adherence in children and potentially the elderly population. This may involve caregivers taking responsibility for the medication or monitoring the patient (i.e., child or adolescent) to ensure that the patient takes his/her AED at the correct dose and time. Increased supervision can also happen at the provider level at clinic visits. When adherence issues are identified, health care providers can engage the patient in an open dialogue to discuss adherence barriers and problem-solve these issues to facilitate adherence. Motivational interviewing (MI), which is a patient-centered clinical approach, has been found to have clinical utility in facilitating patient-provider communication about adherence barriers (Rubak, Sandbaek, Lauritzen, and Christensen, 2005; Suarez and Mullins, 2008). More frequent follow-up clinic visits often allows providers to consistently monitor progress and address adherence problems (i.e., subtherapeutic levels, behavioral issues). For example, an adult patient with substance abuse issues and limited financial resources may choose to spend their financial resources on alcohol or tobacco versus AED medications. MI techniques would provide the opportunity for clinicians to progressively discuss patient motivation to change their behavior. On the other hand, children and adolescents can often experience normative developmental issues (i.e.,
Adherence to Antiepileptic Drug Therapy across the Developmental Life-Span 197 behavioral noncompliance), which can interfere with medication adherence. Strategies such as contingency management and token-economy systems have been found to be effective in addressing behavioral issues that compromise adherence. For example, a young child may have temper tantrums prior to medication dosing due to the medication taste or difficulties with pill swallowing. The implementation of a token-economy system by caregivers can ensure the necessary reinforcement to minimize the frequency of temper tantrums and increase behavioral compliance with AED adherence. Multi-component interventions integrate components of each of the aforementioned interventions to provide a more comprehensive and patient-specific intervention to target adherence behaviors. For example, Behavioral Family Systems Therapy (BFST; (Wysocki, Greco, Harris, Bubb, and White, 2001) targets family communication and problem-solving, but the treatment model has also been adapted to address adherence barriers (Wysocki, et al., 2006; Wysocki, et al., 2000). A recent meta-analysis regarding adherence interventions in pediatric populations suggested that behavioral and multi-component interventions have moderate effects on adherence compared to educational interventions (Kahana, Drotar, and Frazier, 2008). Given the paucity of interventions to address adherence in epilepsy, a critical next step is to develop and evaluate interventions to improve adherence for both pediatric and adult populations. TAKE HOME MESSAGE: Adherence interventions in epilepsy are lacking; however, education, organization, and behavioral strategies to improve adherence can be applied to address epilepsyspecific non-adherence Future research should focus on testing multi-component interventions, which include education about epilepsy and its treatment, behavior and organizational strategies, and family-based problem-solving for children/adolescents
Conclusion Overall, this chapter has highlighted key issues related to AED adherence in individuals with epilepsy, including measurement, predictors, outcomes, and interventions for AED adherence. As we look to the future of optimizing adherence to AEDs and patient healthrelated quality of life, it is imperative to systematically assess and discuss non-adherence within clinical settings. As outlined above, objective electronically-monitored adherence is a reliable and valid tool that has clinical utility but has not been used to its full potential to date. Although the expense of electronic monitors is their primary limitation, the data obtained from this method provides rich and critical data about adherence behaviors that may impact suboptimal seizure control. Using this measurement approach, one area for future research is to examine the natural history of adherence for individuals beginning at diagnosis to better understand patterns of adherence and whether adherence trajectories differentially impact health outcomes. Perhaps there are particular subpopulations that are at increased risk for nonadherence. Identification of these at-risk groups can enable clinicians to provide targeted interventions to those who most need it.
198
Avani C. Modi and Shanna M. Guilfoyle
Within the current clinical care model, there appears to be a ―don‘t ask, don‘t tell‖ policy regarding non-adherence because it often elicits strong reactions on the side of families and healthcare teams. Patients and families may feel a strong need to present well (i.e., high social desirability), which may influence self-reported adherence, and be less likely to openly discuss salient barriers that contribute to non-adherence. Furthermore, healthcare teams may avoid discussions about non-adherence, which could result in inappropriate dosage increases or changes to AEDs that are therapeutically unnecessary. For example, a child who has recently transitioned from a school year to summer vacation may have difficulties remembering to take a morning AED dose because of sleeping in, resulting in seizure recurrence. If this barrier is not acknowledged during a clinic appointment, it is not uncommon for a practitioner to increase the AED dosage to control the seizures. In contrast, open dialogue with patients and families can encourage the identification of barriers to adherence. Specifically, electronic monitors can have significant clinical utility because they can serve to provide a feedback loop to patients and their families during routine clinical care. Such models have been used successfully in the diabetes population through the use of blood glucose monitors, which are often downloaded at every clinic visit. Within our own work using MEMS TrackCaps, we have identified how one missed AED dose resulted in a seizure for a particular child with epilepsy, leading to a discussion of adherence behaviors with the family. In collaboration with this objective data, clinicians can also use self-report measures to further discuss adherence barriers with their patients. Normalizing and problem-solving barriers to adherence, which are identified through multi-method assessment, are the necessary first steps in helping families manage epilepsy. Another important area that has been neglected in epilepsy is the development, implementation, and evaluation of adherence interventions. Open patient-provider communication can provide necessary information to aid in developing these interventions. A critical first step to the development of epilepsy-specific adherence interventions is the identification of key predictors of non-adherence. Critical predictors of AED adherence include: sociodemographic (e.g., lower SES, education), medical (e.g., AED side effects, AED dosing frequency), individual (e.g., beliefs and perceptions about epilepsy, externalizing behaviors in children), family (e.g., conflict), and healthcare (e.g., satisfaction with medical care, positive patient-provider communication) variables. Although these predictors provide initial guidance about ways to facilitate adherence, such as choosing AEDs that require less frequent dosing and are associated with minimal side effects, researchers have yet to study and identify modifiable individual and family factors that impede or facilitate adherence. Specifically, little attention has been dedicated to the role of internalizing symptoms (e.g., depression) on adherence behaviors within epilepsy, although the link is quite strong for other chronic conditions (DiMatteo, Lepper, and Croghan, 2000). Similarly, what role does social support and stigma play on adherence behaviors and how do these differ across the lifespan? Psychosocial factors, such as the ones described above, are most amenable to adherence interventions. With this critical information, we can begin to develop individualized interventions that target patient-specific barriers to epilepsy management. Taken together, investigative efforts to identify additional, yet modifiable psychosocial predictors of adherence are warranted before epilepsy-specific adherence interventions are developed. Through clinical care and routine clinic visits, this information can be obtained via multi-method adherence assessment and patient-provider dialogue about adherence barriers. In turn, healthcare teams should highlight the importance of adherence to families, normalize
Adherence to Antiepileptic Drug Therapy across the Developmental Life-Span 199 non-adherence, and provide a ―safe environment‖ to discuss barriers so that patients with epilepsy and their healthcare teams can work collaboratively to make the best decisions for care. The onus will be on healthcare teams to emphasize monitoring of adherence with electronic monitors, review adherence data from past clinic visits, and prompt discussion of barriers to adherence if they are present. If families are demonstrating excellent adherence, this would be an opportunity to highlight and reinforce behaviors that promote adherence. On the other hand, when barriers are identified, early intervention to improve adherence is warranted, which could potentially change the course of the disease and its outcomes for patients.
References Al-Faris, E. A., Abdulghani, H. M., Mahdi, A. H., Salih, M. A., and Al-Kordi, A. G. (2002). Compliance with appointments and medications in a pediatric neurology clinic at a University Hospital in Riyadh, Saudi Arabia. Saudi Med. J, 23(8), 969-974. Anderson, B., Ho, J., Brackett, J., Finkelstein, D., and Laffel, L. (1997). Parental involvement in diabetes management tasks: relationships to blood glucose monitoring adherence and metabolic control in young adolescents with insulin-dependent diabetes mellitus. J. Pediatr, 130(2), 257-265. Argumosa, A., and Herranz, J. L. (2004). Childhood epilepsy: a critical review of cost-ofillness studies. Epileptic Disord, 6(1), 31-40. Asadi-Pooya, A. A. (2005). Drug compliance of children and adolescents with epilepsy. Seizure, 14(6), 393-395. Asato, M. R., Manjunath, R., Sheth, R. D., Phelps, S. J., Wheless, J. W., Hovinga, C. A., et al. (2009). Adolescent and caregiver experiences with epilepsy. J. Child Neurol, 24(5), 562571. Bassili, A., Omar, T., Zaki, A., Abdel-Fattah, M., and Tognoni, G. (2002). Pattern of diagnostic and therapeutic care of childhood epilepsy in Alexandria, Egypt. Int. J. Qual Health Care, 14(4), 277-284. Baumann, R. J., Ryan, M., and Yelowitz, A. (2004). Physician preference for antiepileptic drug concentration testing. Pediatr Neurol, 30(1), 29-32. Becker, M. H., and Maiman, L. A. (1975). Sociobehavioral determinants of compliance with health and medical care recommendations. Med. Care, 13(1), 10-24. Berg, J. S., Dischler, J., Wagner, D. J., Raia, J. J., and Palmer-Shevlin, N. (1993). Medication compliance: a healthcare problem. Ann. Pharmacother, 27(9 Suppl), S1-24. Besag, F. M. (2001). Behavioural effects of the new anticonvulsants. Drug Saf, 24(7), 513536. Besag, F. M. (2004). Behavioural effects of the newer antiepileptic drugs: an update. Expert Opin. Drug Saf, 3(1), 1-8. Brown, I., Sheeran, P., and Reuber, M. (2009). Enhancing antiepileptic drug adherence: A randomized controlled trial. Epilepsy Behav. Buck, D., Jacoby, A., Baker, G. A., and Chadwick, D. W. (1997). Factors influencing compliance with antiepileptic drug regimes. Seizure, 6(2), 87-93.
200
Avani C. Modi and Shanna M. Guilfoyle
Buelow, J. M., and Smith, M. C. (2004). Medication management by the person with epilepsy: perception versus reality. Epilepsy Behav, 5(3), 401-406. Carr, J. E., Coriaty, S., Wilder, D. A., Gaunt, B. T., Dozier, C. L., Britton, L. N., et al. (2000). A review of "noncontingent" reinforcement as treatment for the aberrant behavior of individuals with developmental disabilities. Res. Dev. Disabil, 21(5), 377-391. Christensen, A. J. (2004). Patient adherence to medical treatment regimens. New Haven and London: Yale University Press. Cramer, J. A. (1995). Microelectronic systems for monitoring and enhancing patient compliance with medication regimens. Drugs, 49(3), 321-327. Cramer, J. A., Glassman, M., and Rienzi, V. (2002). The relationship between poor medication compliance and seizures. Epilepsy Behav, 3(4), 338-342. Cramer, J. A., Mattson, R. H., Prevey, M. L., Scheyer, R. D., and Ouellette, V. L. (1989). How often is medication taken as prescribed? A novel assessment technique. Jama, 261(22), 3273-3277. Cramer, J. A., Roy, A., Burrell, A., Fairchild, C. J., Fuldeore, M. J., Ollendorf, D. A., et al. (2008). Medication compliance and persistence: terminology and definitions. Value Health, 11(1), 44-47. Cramer, J. A., Scheyer, R. D., and Mattson, R. H. (1990). Compliance declines between clinic visits. Arch. Intern. Med, 150(7), 1509-1510. Cramer, J. A., Vachon, L., Desforges, C., and Sussman, N. M. (1995). Dose frequency and dose interval compliance with multiple antiepileptic medications during a controlled clinical trial. Epilepsia, 36(11), 1111-1117. Csikszentmihalyi, M., and Larson, R. (1987). Validity and reliability of the ExperienceSampling Method. J. Nerv. Ment. Dis, 175(9), 526-536. Dawson, K. P., and Jamieson, A. (1971). Value of blood phenytoin estimation in management of childhood epilepsy. Archives of the Disease in Childhood, 46, 386-388. Dew, M. A., Dunbar, J. J., Switzer, G. E., DiMartini, A. F., Stilley, C., and Kormos, R. L. (2001). Adherence to the medical regimen in transplantation. In J. R. Rodrigue (Ed.), Biopsychosocial perspectives in transplantation (pp. 93-124). New York: Kluwer Academic Publishers/Plenum Publishers. DiMatteo, M. R. (2004a). Social support and patient adherence to medical treatment: a metaanalysis. Health Psychol, 23(2), 207-218. DiMatteo, M. R. (2004b). Variations in patients' adherence to medical recommendations: a quantitative review of 50 years of research. Med. Care, 42(3), 200-209. DiMatteo, M. R., Giordani, P. J., Lepper, H. S., and Croghan, T. W. (2002). Patient adherence and medical treatment outcomes: a meta-analysis. Med. Care, 40(9), 794-811. DiMatteo, M. R., Lepper, H. S., and Croghan, T. W. (2000). Depression is a risk factor for noncompliance with medical treatment. Archives of Internal Medicine, 160, 2101-2107. Dodrill, C. B., Batzel, L. W., Wilensky, A. J., and Yerby, M. S. (1987). The role of psychosocial and financial factors in medication noncompliance in epilepsy. Int. J. Psychiatry Med, 17(2), 143-154. Doughty, J., Baker, G. A., Jacoby, A., and Lavaud, V. (2003). Cross-cultural differences in levels of knowledge about epilepsy. Epilepsia, 44(1), 115-123. Dunbar-Jacob, J., and Mortimer-Stephens, M. K. (2001). Treatment adherence in chronic disease. J. Clin. Epidemiol, 54 Suppl 1, S57-60.
Adherence to Antiepileptic Drug Therapy across the Developmental Life-Span 201 Eiser, C. (1993). Growing up with a chronic disease: The impact on children and their families. London: Kingsley. Eisler, J., and Mattson, R. H. (1975). Compliance in anticonvulsant drug therapy. Unpublished abstract. Ettinger, A. B., Manjunath, R., Candrilli, S. D., and Davis, K. L. (2009). Prevalence and cost of nonadherence to antiepileptic drugs in elderly patients with epilepsy. Epilepsy Behav, 14(2), 324-329. Faught, E., Duh, M. S., Weiner, J. R., Guerin, A., and Cunnington, M. C. (2008). Nonadherence to antiepileptic drugs and increased mortality: findings from the RANSOM Study. Neurology, 71(20), 1572-1578. Faught, R. E., Weiner, J. R., Guerin, A., Cunnington, M. C., and Duh, M. S. (2009). Impact of nonadherence to antiepileptic drugs on health care utilization and costs: findings from the RANSOM study. Epilepsia, 50(3), 501-509. Finney, J. W., Hook, R. J., Friman, P. C., Rapoff, M. A., and Christophersen, E. R. (1993). The overestimation of adherence to pediatric medical regimens. Child Health Care, 22(4), 297-304. Freund, A., Johnson, S. B., Silverstein, J., and Malone, J. (1991). The relationship between adherence behaviors and metabolic control in childhood diabetes. Advances in child health psychology, 277-284. Friedman, I. M., Litt, I. F., King, D. R., Henson, R., Holtzman, D., Halverson, D., et al. (1986). Compliance with anticonvulsant therapy by epileptic youth. Relationships to psychosocial aspects of adolescent development. J. Adolesc. Health Care, 7(1), 12-17. Gomes, M., and Maia Filho, H. (1998). Medication-taking behavior and drug self regulation in people with epilepsy. Arq. Neuropsiquitr, 56(4), 714-719. Gopinath, B., Radhakrishnan, K., Sarma, P. S., Jayachandran, D., and Alexander, A. (2000). A questionnaire survey about doctor-patient communication, compliance and locus of control among south Indian people with epilepsy. Epilepsy Res, 39(1), 73-82. Goulle, J. P., Noyon, J., Layet, A., Rapoport, N. F., Vaschalde, Y., Pignier, Y., et al. (1995). Phenobarbital in hair and drug monitoring. Forensic. Sci. Int, 70(1-3), 191-202. Haynes, R. B., Sackett, D. L., Gibson, E. S., Taylor, D. W., Hackett, B. C., Roberts, R. S., et al. (1976). Improvement of medication compliance in uncontrolled hypertension. Lancet, 1(7972), 1265-1268. Hazzard, A., Hutchinson, S. J., and Krawiecki, N. (1990). Factors related to adherence to medication regimens in pediatric seizure patients. J. Pediatr Psychol, 15(4), 543-555. Helgeson, D. C., Mittan, R., Tan, S. Y., and Chayasirisobhon, S. (1990). Sepulveda Epilepsy Education: the efficacy of a psychoeducational treatment program in treating medical and psychosocial aspects of epilepsy. Epilepsia, 31(1), 75-82. Herkes, G. K., and Eadie, M. J. (1990). Possible roles for frequent salivary antiepileptic drug monitoring in the management of epilepsy. Epilepsy Res, 6(2), 146-154. Hovinga, C. A., Asato, M. R., Manjunath, R., Wheless, J. W., Phelps, S. J., Sheth, R. D., et al. (2008). Association of non-adherence to antiepileptic drugs and seizures, quality of life, and productivity: survey of patients with epilepsy and physicians. Epilepsy Behav, 13(2), 316-322. Jasti, S., Siega-Riz, A. M., Cogswell, M. E., and Hartzema, A. G. (2006). Correction for errors in measuring adherence to prenatal multivitamin/mineral supplement use among low-income women. J. Nutr, 136(2), 479-483.
202
Avani C. Modi and Shanna M. Guilfoyle
Johnson, S. B. (1995). Managing insulin-dependent diabetes mellitus in adolescence: A developmental perspective. In J. L. Wallander and L. J. Siegel (Eds.), Adolescent health problems: Behavioral perspectives (pp. 265-288). New York: Guilford Press. Johnson, S. B., Silverstein, J., Rosenbloom, A., Carter, R., and Cunningham, W. (1986). Assessing daily management in childhood diabetes. Health Psychol, 5(6), 545-564. Jones, R. M., Butler, J. A., Thomas, V. A., Peveler, R. C., and Prevett, M. (2006). Adherence to treatment in patients with epilepsy: Associations with seizure control and illness beliefs. Seizure, 15(7), 504-508. Kahana, S., Drotar, D., and Frazier, T. (2008). Meta-analysis of psychological interventions to promote adherence to treatment in pediatric chronic health conditions. J. Pediatr Psychol, 33(6), 590-611. Kahneman, D., Krueger, A. B., Schkade, D. A., Schwarz, N., and Stone, A. A. (2004). A survey method for characterizing daily life experience: the day reconstruction method. Science, 306(5702), 1776-1780. Kanner, A. M. (2003). Depression in epilepsy: a frequently neglected multifaceted disorder. Epilepsy Behav, 4 Suppl 4, 11-19. Kemp, S., Feely, M., Hay, A., Wild, H., and Cooper, C. (2007). Psychological factors and use of antiepileptic drugs: pilot work using an objective measure of adherence. Psychol. Health Med, 12(1), 107-113. Kobau, R., and DiIorio, C. (2003). Epilepsy self-management: a comparison of self-efficacy and outcome expectancy for medication adherence and lifestyle behaviors among people with epilepsy. Epilepsy Behav, 4(3), 217-225. Koumoutsos, J. E., Modi, A. C., Morita, D. A., Monahan, S. R., and Glauser, T. A. (2007). The dual clinical impact of non-adherence: Seizures and ―avoidable‖ AED dosage increases [Abstract] Epilepsia, 48(S6), 56-57. Kwong, K. L., Wong, S. N., and So, K. T. (2000). Parental perception, worries and needs in children with epilepsy. Acta Paediatr, 89(5), 593-596. Kyngas, H. (2000a). Compliance of adolescents with chronic disease. J. Clin. Nurs, 9(4), 549556. Kyngas, H. (2000b). Compliance with health regimens of adolescents with epilepsy. Seizure, 9(8), 598-604. La Greca, A. M., and Bearman, K. J. (2003). Adherence to prescribed medical regimens. In M. C. Roberts (Ed.), Handbook of Pediatric Psychology (3rd ed., pp. 119-140). New York: Guilford. La Greca, A. M., Follansbee, D., and Sklyar, J. S. (1990). Developmental and behavioral aspects of diabetes management in youngsters. Children's Health Care, 19, 132-139. La Greca, A. M., and Schuman, W. B. (1995). Adherence to prescribed medical regimens. In M. C. Roberts (Ed.), Handbook of Pediatric Psychology (2nd ed., pp. 55-83). New York: Guilford. Leestma, J. E., Walczak, T., Hughes, J. R., Kalelkar, M. B., and Teas, S. S. (1989). A prospective study on sudden unexpected death in epilepsy. Ann. Neurol, 26(2), 195-203. Lemanek, K. (1990). Adherence issues in the medical management of asthma. J. Pediatr Psychol, 15(4), 437-458. Leventhal, H., Safer, M. A., and Panagis, D. M. (1983). The impact of communications on the self-regulation of health beliefs, decisions, and behavior. Health Educ. Q, 10(1), 3-29.
Adherence to Antiepileptic Drug Therapy across the Developmental Life-Span 203 Lund, L. (1974). Anticonvulsant effect of diphenylhydantoin relative to plasma levels. A prospective three-year study in ambulant patients with generalized epileptic seizures. Arch. Neurol, 31(5), 289-294. Manjunath, R., Davis, K. L., Candrilli, S. D., and Ettinger, A. B. (2009). Association of antiepileptic drug nonadherence with risk of seizures in adults with epilepsy. Epilepsy Behav, 14(2), 372-378. Mattson, R. H., Cramer, J. A., and Collins, J. F. (1988). Aspects of compliance: taking drugs and keeping clinic appointments. Epilepsy Res. Suppl, 1, 111-117. McQuaid, E. L., Kopel, S. J., Klein, R. B., and Fritz, G. K. (2003). Medication adherence in pediatric asthma: reasoning, responsibility, and behavior. J. Pediatr Psychol, 28(5), 323333. Mei, Z., and Williams, J. (1997). Simultaneous determination of phenytoin and carbamazepine in human hair by high-performance liquid chromatography. Ther Drug Monit, 19(1), 92-94. Mellins, C. A., Brackis-Cott, E., Dolezal, C., and Abrams, E. J. (2004). The role of psychosocial and family factors in adherence to antiretroviral treatment in human immunodeficiency virus-infected children. Pediatr Infect. Dis. J, 23(11), 1035-1041. Mitchell, W. G., Scheier, L. M., and Baker, S. A. (2000). Adherence to treatment in children with epilepsy: who follows "doctor's orders"? Epilepsia, 41(12), 1616-1625. Modi, A. C., Crosby, L. E., Guilfoyle, S. M., Lemanek, K. L., Witherspoon, D., and Mitchell, M. J. (2009). Barriers to treatment adherence for pediatric patients with sickle cell disease and their families. Children's Health Care(38), 107-122. Modi, A. C., Guilfoyle, S. M., Koumoutsos, J. E., Morita, D. A., Monahan, S. R., and Glauser, T. A. (2008). How do we best measure adherence to AED therapy in pediatric epilepsy?[Abstract]. Epilepsia, 49(S7), 228. Modi, A. C., Marciel, K. K., Slater, S. K., Drotar, D., and Quittner, A. L. (2008). The influence of parental supervision on medical adherence in pre and late-adolescents with cystic fibrosis: Developmental shifts from early to late adolescence. Children’s Health Care, 37(1), 78-92. Modi, A. C., Morita, D. A., and Glauser, T. A. (2008). One-month adherence in children with new-onset epilepsy: white-coat compliance does not occur. Pediatrics, 121(4), e961-966. Modi, A. C., and Quittner, A. L. (2006a). Barriers to Treatment Adherence for Children with Cystic Fibrosis and Asthma: What Gets in the Way? J. Pediatr Psychol, 31(8), 846-858. Modi, A. C., and Quittner, A. L. (2006b). Utilizing computerized phone diary procedures to assess health behaviors in family and social contexts. Children's Health Care, 35, 29-45. Morisky, D. E., Green, L. W., and Levine, D. M. (1986). Concurrent and predictive validity of a self-reported measure of medication adherence. Med. Care, 24(1), 67-74. Neuspiel, D. R., and Kuller, L. H. (1985). Sudden and unexpected natural death in childhood and adolescence. JAMA, 254(10), 1321-1325. Otero, S., and Hodes, M. (2000). Maternal expressed emotion and treatment compliance of children with epilepsy. Dev. Med. Child Neurol, 42(9), 604-608. Paschal, A. M., Hawley, S. R., St Romain, T., and Ablah, E. (2008). Measures of adherence to epilepsy treatment: review of present practices and recommendations for future directions. Epilepsia, 49(7), 1115-1122. Perucca, E. (2001). The management of refractory idiopathic epilepsies. Epilepsia, 42 Suppl 3, 31-35.
204
Avani C. Modi and Shanna M. Guilfoyle
Perucca, E. (2002). Patient-tailored antiepileptic drug therapy: predicting response to antiepileptic drugs International Congress Series, 1244, 93-103 Peterson, G. M., McLean, S., and Millingen, K. S. (1982). Determinants of patient compliance with anticonvulsant therapy. Epilepsia, 23(6), 607-613. Peterson, G. M., McLean, S., and Millingen, K. S. (1984). A randomised trial of strategies to improve patient compliance with anticonvulsant therapy. Epilepsia, 25(4), 412-417. Phipps, S., and DeCuir-Whalley, S. (1990). Adherence issues in pediatric bone marrow transplantation. J. Pediatr Psychol, 15(4), 459-475. Quittner, A. L., and DiGirolamo, A. M. (1998). Family adaptation to childhood disability and illness. In R. T. A. J. V. Campo (Ed.), Handbook of Pediatric Psychology and Psychiatry (Vol. II, pp. 70-102). Boston: Allyn and Bacon. Quittner, A. L., Espelage, D. L., Ievers-Landis, C. E., and Drotar, D. (2000). Measuring adherence to medical treatments in childhood chronic illness: Considering multiple methods and sources of information. Journal of Clinical Psychology in Medical Settings, 7, 41-54. Quittner, A. L., Modi, A. C., Lemanek, K. L., Ievers-Landis, C. E., and Rapoff, M. A. (2008). Evidence-based assessment of adherence to medical treatments in pediatric psychology. J. Pediatr Psychol, 33(9), 916-936; discussion 937-918. Quittner, A. L., and Opipari, L. C. (1994). Differential treatment of siblings: interview and diary analyses comparing two family contexts. Child Dev, 65(3), 800-814. Rand, C. S. (2000). "I took the medicine like you told me doctor": Self report of adherence with medical regimens. In A. Stone, J. S. Tukkan, C. M. Bachrael, J. B. Jobe, H. J. Kurtzman and V. S. Cain (Eds.), The science of self-report (pp. 257-276). Mahway, NJ: Lawrence Erlbaum Associates. Rand, C. S. (2005). Patient adherence with COPD therapy. Eur Respir Rev, 14(96), 97-101. Rapoff, M. A. (1999). Adherence to Pediatric Medical Regimens. New York, NY: Kluwer Academic/Plenum Publishers. Rodenburg, R., Stams, G. J., Meijer, A. M., Aldenkamp, A. P., and Dekovic, M. (2005). Psychopathology in children with epilepsy: a meta-analysis. J. Pediatr Psychol, 30(6), 453-468. Rubak, S., Sandbaek, A., Lauritzen, T., and Christensen, B. (2005). Motivational interviewing: a systematic review and meta-analysis. Br J Gen Pract, 55(513), 305-312. Shope, J. T. (1988). Compliance in children and adults: review of studies. Epilepsy Res. Suppl, 1, 23-47. Shore, C., Austin, J., Musick, B., Dunn, D., McBride, A., and Creasy, K. (1998). Psychosocial care needs of parents of children with new-onset seizures. 3. J. Neurosci. Nurs, 30(3), 169-174. Snodgrass, S. R., and Parks, B. R. (2000). Anticonvulsant blood levels: historical review with a pediatric focus. J. Child Neurol, 15(11), 734-746. Snodgrass, S. R., Vedanarayanan, V. V., Parker, C. C., and Parks, B. R. (2001). Pediatric patients with undetectable anticonvulsant blood levels: comparison with compliant patients. J. Child Neurol, 16(3), 164-168. Stanaway, L., Lambie, D. G., and Johnson, R. H. (1985). Non-compliance with anticonvulsant therapy as a cause of seizures. N. Z. Med. J, 98(774), 150-152. Suarez, M., and Mullins, S. (2008). Motivational interviewing and pediatric health behavior interventions. J. Dev. Behav. Pediatr, 29(5), 417-428.
Adherence to Antiepileptic Drug Therapy across the Developmental Life-Span 205 Takaki, S., Kurokawa, T., and Aoyama, T. (1985). Monitoring drug noncompliance in epileptic patients: assessing phenobarbital plasma levels. Ther Drug Monit, 7(1), 87-91. Tebbi, C. K., Cummings, K. M., Zevon, M. A., Smith, L., Richards, M., and Mallon, J. (1986). Compliance of pediatric and adolescent cancer patients. Cancer, 58(5), 11791184. Urquhart, J., and Chevalley, C. (1988). Impact of unrecognized dosing errors on the cost and effectiveness of pharmaceuticals. Drug Information Journal, 22, 363-378. Vazquez, B., and Devinsky, O. (2003). Epilepsy and anxiety. Epilepsy Behav, 4 Suppl 4, S2025. Wang, E., and Haynes, R. B. (1988). Compliance with antimicrobial therapy in children. In G. Koren, C. G. Prober and R. Gold (Eds.), Antimicrobial therapy in infants and children (pp. 105-114). New York: Marcel Dekker. Wiener, L., Riekert, K. A., Ryder, C., and Wood, L. V. (2004). Assessing medication adherence in adolescents with HIV when electronic monitoring is not feasible. AIDS Patient Care STDS, 18(9), 527-538. Williams, J., Myson, V., Steward, S., Jones, G., Wilson, J. F., Kerr, M. P., et al. (2002). Selfdiscontinuation of antiepileptic medication in pregnancy: detection by hair analysis. Epilepsia, 43(8), 824-831. World-Health-Organization (2003). Adherence to long-term therapies: Evidence for action. Geneva, Switzerland: World Health Organization. Wysocki, T., Greco, P., Harris, M. A., Bubb, J., and White, N. H. (2001). Behavior therapy for families of adolescents with diabetes: maintenance of treatment effects. Diabetes Care, 24(3), 441-446. Wysocki, T., Harris, M. A., Buckloh, L. M., Mertlich, D., Lochrie, A. S., Taylor, A., et al. (2006). Effects of Behavioral Family Systems Therapy for Diabetes on Adolescents' Family Relationships, Treatment Adherence, and Metabolic Control. J. Pediatr Psychol, 31(9), 928-938. Wysocki, T., Harris, M. A., Greco, P., Bubb, J., Danda, C. E., Harvey, L. M., et al. (2000). Randomized, controlled trial of behavior therapy for families of adolescents with insulindependent diabetes mellitus. J. Pediatr Psychol, 25(1), 23-33. Zindani, G. N., Streetman, D. D., Streetman, D. S., and Nasr, S. Z. (2006). Adherence to treatment in children and adolescent patients with cystic fibrosis. J. Adolesc. Health, 38(1), 13-17.
In: Society, Behaviour and Epilepsy Editors: Jaya Pinikahana and Christine Walker
ISBN 978-1-61761-001-1 © 2011 Nova Science Publishers, Inc.
Chapter XII
Social Competence and Children with Epilepsy K. Rantanen, 1, 2 K. Eriksson 2, 3 and P. Nieminen 1 1. University of Tampere, Department of Psychology, Finland 2. Tampere University Hospital, Department of Pediatric Neurology, Finland 3. University of Tampere, Pediatric Research Centre, Medical School, Finland
Abstract The purpose of this chapter is to review social issues associated with childhood epilepsy. Social development is one of the key areas of development and has been associated with later behavioral, social and academic success. Particularly, in children with chronic illness social competence is essential for favorable long-term outcomes. Children with epilepsy are at risk of developing behavioral problems and impaired social competence. After a brief summary of definitions of social competence, this chapter will focus on the current knowledge about social competence, including behavior problems related to epilepsy. Protective factors are also considered. Social competence: This section begins with defining social competence. Social competence may be considered comprising four subcomponents; social skills, sociocognitive skills, absence of problem behaviour and prosocial behaviour. These subcomponents are prerequisite skills necessary for socially competent behaviour. Despite the definitions of social competence and the emphasis on social skills and prosocial behaviour, the majority of the assessment methods used in studies focus on one or two aspects of social competence, for example only the presence of behavior problems.
Correspondence: Kati Rantanen, Neuropsychologist, Lic. A. (Psych.), Department of Psychology, University of Tampere and Pediatric Neurology Unit, Department of Pediatrics, Tampere University Hospital, Tampere, Finland. Tel: +358 3 3551 7344, Fax: +358 3 3551 7345, E-mail:
[email protected].
208
K. Rantanen, K. Eriksson and P. Nieminen Epilepsy, behavior and social competence: This section briefly reviews a body of literature demonstrating factors associating with social competence amongst children with epilepsy. Factors contributing to social competence in children with epilepsy are multi-factorial in nature. Mediators or possible predictors of lower social competence are discussed. Although, some mediators are related to epilepsy, more important moderators seem to be related to cognitive, family and environmental factors. However, there is still a lack of knowledge on the pathways of risk-factors, mediators and social competence. Implications on clinical practice: The need for early assessment and identification of deficits in social competence in children are emphasized. In clinical practice and epilepsy guidance, attention should be paid to the development of social skills and behavior of these children with epilepsy in order to support acquisition of age appropriate social skills and overall psychosocial development. It is important to support the overall psychosocial development and acquisition of age appropriate social skills. In order to promote peer relations, normal, age-appropriate physical and social participation should be encouraged in children with epilepsy. Conclusions: Although, risk factors for behavioural problems and psychopathology have been identified in children with epilepsy, the development of social competence in children with epilepsy should be studied further to increase our understanding of the possible developmental pathways to behavioral problems. These longitudinal studies are needed. This would also be beneficial regarding early intervention. Developmental, social and behavioral problems in early childhood may have long-lasting effects in later development and therefore the clinical implications of further studies are important.
Introduction Social development is one of the core areas of development and the development of social competence has been associated with later behavioral, social and academic success (Malone, 2007). Children‘s social functioning or competence is regarded as one of the best indicators of current and future behavioral and emotional problems (John, 2001). It is well known that children with chronic central nervous system (CNS) -related conditions, like epilepsy have an increased risk of developing behavioral problems (e.g. Nassau and Drotar, 1997) or mental health problems (Noeker, Haverkamp-Krois and Haverkamp, 2005), hence lower social competence. Childhood years are a rapid phase of cognitive and social development. Psychosocial tasks, like behavior or self control and compliance (e.g. the ability to develop and maintain frendships, to control one‘s behavior, to comply with parent‘s request) reflect domains of social competence (Masten and Coatsworth, 1998). Achieving social competence is critical in order to function successfully later in school and with peers. A socially competent person is able to achieve personal goals in social interaction and to maintain positive relationships with others (Rose-Krasnor, 1997). The aim of this chapter is to present a review of relevant research into social and behavioral issues relating to social competence and childhood epilepsy. First, definitions of social competence are briefly presented in order to provide an insight to different aspects of competent behavior. Secondly, issues and deficits regarding social competence are considered on the basis of studies conducted among children with epilepsy. Finally, in order to understand developmental pathways in children with epilepsy, it is important to consider possible risk factors as well as protective or resilience factors affecting different courses of the child‘s development.
Social Competence and Children with Epilepsy
209
Defining Social Competence In general, the term competence refers to children‘s ability to adapt in their environment (Mash and Wolfe, 1999). However, there is no single generally accepted definition of social competence. Rather, definitions vary and different concepts like social skills, adaptive behavior, social functioning and social adjustment are used to refer to social competence. Despite this variety of concepts, some definitions related to social issues and competence in children are included here in order to provide a loose framework for understanding research in the field. First, from the developmental perspective Doll (1965, 1977) has defined social competence broadly as the individual‘s ability to function equivalent to age-appropriate and cognitive abilities. Social competence refers to the means of achieving the major developmental tasks expected of a child of a given age and gender in the context of his/her own culture, society and time (Achenbach, 1991). This also means the flexibility and ability to solve developmental problems and to adapt to different social contexts and demands (Masten and Coatsworth, 1998). The broader concept of ‗social competence‘ is usually understood as comprising subcomponents. For instance, Gresham and Elliott‘s (1987) definition of social competence differentiates between concepts social skills and social competence. The latter comprised two subdomains: adaptive behavior and social skills. Social skills refers to specific behaviors required to perform specific tasks competently. Social competence is regarded as an evaluative term based upon judgements that the person has performed a task adequately (Gresham and Elliot, 1987). Rose-Krasnor (1997) defines social competence as effectiveness in interaction. In her model, there is a basic distinction between self and other with both being necessary for good adjustment. Skill levels for social competence include the social, emotional and cognitive abilities and motivations associated with social competence. Behaviors like popularity and social acceptance or failure and motivations comprise the building blocks of interactions, relationships and group status. However, Rose-Krasnor (1997) emphasises that attributes (like skills, traits and motivations) of social competence cannot be assessed separately from their effectiveness in helping the child to achieve interpersonal, social goals and establishing positive relationships with peers. McCabe and Meller (2004) define social competence simply as a repertoire of skills, including knowledge of social standards of behavior, social problem solving, emotion recognition and understanding and communication. This definition covers some of the main aspects of the concept: cultural rules of social competence i.e. appropriate behavior and special skills (e.g. social problems solving skills, emotion prosessing and cognitive skills) needed to accomplish such behavior. Also, Cavell‘s (1990) model defines social competence as a multilevel construct comprising subcomponents of social adjustment, social performance and social skills. This tri-component model of social competence is considered to be sensitive to the effects of CNS conditions (like epilepsy or cerebral palsy). Although, conceptualizations of social competence vary, there is an agreement that social competence refers to a global judgement and is based on behavioral performance (Gresham, 1986). All of these definitions emphasize the importance of a person's ability to function as expected in his/her social environment and culture. Rose-Krasnor (1997) points out that social competence is a flexible, multidimensional construct of adaptive and effective functioning.
210
K. Rantanen, K. Eriksson and P. Nieminen
Underlying CNS lesions and dysfunctions
Family and environment (e.g. parenting style, stigma)
Epilepsy factors (e.g. age at onset, seizure frequency)
Neurocognitive factors (e.g. mental retardation, attention problems)
Social skils
Sociocognitive skills
Absence of behavior problems
Prosocial behavior
Social competence Figure 1. A conceptual framework of social competence and its subcomponents in childhood epilepsy.
We have summarized some of the key aspects of the definitions by presenting a conceptual framework of social competence and its subcomponents in childhood epilepsy in Figure 1. First, it is clear that the association between epilepsy and social competence is complex and no direct causality has been demonstrated. But, both pathophysiological (i.e. CNS dysfunction or lesions) and environmental factors, including family-related factors may affect the development of social competence. This effect may be direct or mediated through epilepsy related and/or neurocognitive factors which in turn may also have an independent effect on the development of social competence (see also Noeker et al., 2005). Moreover, social competence may be considered as comprising at least four subcomponents. These subcomponents include social skills, socio-cognitive skills, absence of problem behaviors and prosocial behaviors. These subcomponents may be considered as basic or prerequisite skills necessary for socially competent behavior. Cognitive, social and emotional skills form the basis of social competence. Social skills usually refers to a repertoire of basic skills like the ability to start conversations and take turns. Socio-cognitive skills include for example the ability to detect and decode social cues, to generate responses in social situations and the accuracy of these functions (Dodge and Feldman, 1990). These skills are prerequisite for a child to be able to encode and interpret social situations and problems, and execute and evaluate plans to solve problems arising in social situations (Rose-Krasnor, 1997). There is some evidence that those children that are rejected by peers are less skillful at interpreting cues, or are biased in their attributions of others and have a tendency to generate more deviant responses (Dodge and Feldman, 1990). Therefore, impairment of these prerequisite basic socio-cognitive skills is also a risk factor for lower social competence in typically developing children. In addition to social and sociocognitive skills, the manifestation of prosocial i.e. socially desirable actions and absence of
Social Competence and Children with Epilepsy
211
behavior problems or antisocial behavior (e.g. aggression and disruptive behavior) are considered to be the main aspects of social competence (Junttila, Voeten, Kaukiainen and Vauras, 2006). Socially competent behavior with peers reflects effective social interactions (Rose-Krasnor, 1997).
Deficits in Social Competence Social incompetence may be classified into four types: skill deficit, performance deficit, self-control skill deficit or self-control performance deficit (Gresham and Elliot, 1987). In skill deficit, a child has not learned the requisite social skills to behave in either an adaptive or socially skilled manner. With regards to performance deficit, a child has the knowledge and skills to perform a given behavior, but fails to perform it at an acceptable level (Gresham and Elliot, 1987; see also Kavale and Forness, 1996). Therefore, maladaptive behavior, behavioral problems and / or psychopathology may be considered as areas of undesirable behaviors that may interfere with the development of the child‘s social competence. Deficits in social competence may also be attributed to poor social skills or peer acceptance where socially unskilled children are considered to be less popular with peers (Gresham, 1986). There is evidence supporting the relationship between self-regulation, emotionality and social competence and later adjustment (Denham et al., 2003; Fabes and Eisenberg, 1999). Both regulation skills and emotionality may influence children‘s social competence with peers. There are certain behavior patterns, especially aggression and withdrawal that increase the children‘s risk for peer rejections and loss of friendships (Ladd, 1999). Antisocial behavior, related to behavioral, psychiatric and neurocognitive problems, particularly impulse inhibition and disruptive behavior are regarded as aspects of social incompetence (Junttila et al., 2006). Behavioral disorders or maladaptive behavior are usually classified into internalized and externalized problems (Achenbach, 1991). Internalized problems refer to a person‘s inner problems, for example depression and anxiety that are sometimes difficult to detect from overt behavior. Conversly, the externalized problems refer to aggression, conduct problems and destructive behavior that are clearly detectable and interfering with social interaction. Some of the key behavioral dimensions of children's social competence include prosocial behavior, externalizing behavior, and social withdrawal (Diener and Kim). Socially competent behavior with peers reflects effective social interactions (Rose-Krasnor, 1997). Operational definitions and assessments of social competence focus on outcomes (like peer acceptance), underlying social or cognitive skills or observable content associated with social competence. The majority of the assessments methods used in epilepsy related studies of social competence have focused on one or two aspects of social competence, for example on the presence of behavior problems. Hence, the absence of a psychiatric diagnosis and/or emotional and behavioral problems as observed by parents and/or teachers is often regarded as indicating socially competent behavior. Several different parent-, teacher- and child-reports and questionnaires have been developed for the assessment of children‘s social competence. In most of these instruments, the parent, teacher or child assesses the frequency of a given behavior. The most frequently used rating scales include Child Behavior Checklist (CBCL) (Achenbach, 1991, 1992) and Conners‘ Parent Rating Scales – Revised (CPRS-R) (Conners,
212
K. Rantanen, K. Eriksson and P. Nieminen
1997). In addition to questionnaires, some studies have used structured diagnostic interviews, such as Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS) (Kaufman and Birmaher, 1997). Instead of behavior problems, some scales focus on adaptive behavior e.g. Vineland Scales (Doll, 1965 , 1977; Sparrow, Balla and Cicchetti Hamiwka, 1984), or on social skills, e.g. Social Skills Rating Scale (SSRS) (Gresham and Elliot, 1990) or on peer relationships and prosocial behavior, e.g. Strengths and Difficulties Questionnaire (SDQ) (Goodman, 1997). Most studies on social competence and behavior in children with epilepsy have been conducted with CBCL (Rodenburg, Stams, Meijer, Aldenkamp and Dekovic, 2005b). For instance, assessments of social skills and prosocial behavior are mostly lacking in epilepsy research. Moreover, instead of peer report data, studies have focused on parent and teacher reports. The assessment of social competence is based on outcomes rather than on the skill level or on the subcomponents.
Social Competence and Children with Epilepsy In the field of epilepsy research field, social competence is an area of ongoing research. The main focus of these studies has been on behavior problems and psychopathology. Children with central nervous system condition have an increased risk for behavioral problems. Therefore, epilepsy may be regarded as a pervasive condition that includes seizures, cognitive, behavioral and emotional problems (Plioplys, Dunn and Caplan 2007). A large and growing body of literature that has been published on behavioral and social issues in pediatric epilepsy demonstrates that the children with epilepsy have an increased risk of developing behavioral problems (Dunn and Austin, 1999; Nassau and Drotar, 1997). Results indicate increased levels of behavioral problems and psychopathology in children with epilepsy when compared to healthy children (Caplan et al., 2002; Caplan, Siddarth, Gurbani, Ott, Sankar and Shields, 2004; Caplan et al., 2005; Jakovljevic and Martinovic, 2006; Oostrom, Schouten, Kruitwagen, Peters and Jennekens-Schinkel, 2003a; Oostrom, SmeetsSchouten, Kruitwagen, Peters and Jennekens-Schinkel, 2003b), siblings (Austin, Harezlak, Dunn, Huster, Rose and Ambrosius, 2001; Austin, Dunn, Caffrey, Perkins, Harezlak and Rose, 2002) and children with other chronic conditions (Davies, Heyman and Goodman, 2003; McDermott, Mani and Krishnawami, 1995). However, there is great variation in the occurrences of psychiatric problems in children with epilepsy, ranging from 16 % to 60% (Davies et al., 2003; Keene et al., 2005; Ott et al., 2003). Several reviews have been conducted over the past years of the psychopathology or behavioral problems associated with epilepsy (for example Austin and Caplan, 2007; Dunn, 2003; Leonard and George, 1999; Plioplys et al., 2007; Rodenburg et al., 2005b). On the basis of these reviews, attention problems and thought problems are regarded as specific to epilepsy. Similarly, internalizing and social problems are also relatively specific to epilepsy. Internalizing problems reported in children with epilepsy include for example anxiety and depression (Austin et al., 2002; Keene et al., 2005; Schoenfeld et al., 1999). Also, externalizing problems (e.g. aggression, disruptive behavior) have been reported in children with epilepsy (Keene et al., 2005). Externalizing and disruptive disorders and impaired social communication in particular have been found to predict lower social competence scores
Social Competence and Children with Epilepsy
213
(Caplan et al., 2002). In addition, children with epilepsy had lower scores on sociability and the activities when compared with their peers (Jakovljevic and Martinovic, 2006). Multiple factors including additional neurological impairment, neurocognitive deficits, intractable seizures and family related problems have been consistently reported to increase risk of behavioral problems in children with epilepsy (Dunn, 2003). In the following subsections these risk factors will be considered.
Epilepsy Related Factors and Social Competence There is evidence that behavior problems are associated with CNS or epilepsy related variables. First, and perhaps the most important risk factor for lower social compentece is underlying CNS lesion or dysfunction. With respect to etiology, cryptegenic or symptomatic epilepsy seems to have a strong association with both cognitive and behavioral problems. Symptomatic epilepsy refers to epileptic seizures with known etiology (e.g. as the result of identifiable structural lesions of the brain) (Engel, 2001). Idiopathic epilepsy refers to epilepsies with no underlying structural brain lesion or to age-dependent clinical manifestation and assumable genetic etiology (Engel, 2006; Hommet, Sauerwein, DeToffol and Lassonde, 2006). Most idiopathic epilepsies are uncomplicated which implies that there are no other neurological signs or symptoms and cognition is within normal range or only slightly impaired (Elger, Helmstaedter and Kurthen, 2004; Hommet et al., 2006; Mandelbaum and Burack, 1997; Motamedi and Meador, 2003). In this chapter children with epilepsy but without any associated neurological disorder or other chronic illnesses are referred to as uncomplicated epilepsy and children with epilepsy and other neurological signs or symptoms are referred to as complicated epilepsy. Adaptive behavior has been found to be impaired at the time of initial diagnosis in children with an underlying symptomatic etiology or a syndrome (i.e. epileptic encephalopathies) (Berg et al., 2004). Further, these children showed a significant decline in adaptive behavior scores at that time. Children with complicated epilepsy are reported to have fewer age-appropriate social skills and more attention and behavior problems than healthy children (Rantanen, Timonen, Hagström, Hämäläinen, Eriksson and Nieminen, 2009). Moreover, children with cryptogenic rather than those with idiopathic epilepsy are found to have more behavioral problems than their healthy classmates (Oostrom et al., 2003a). Studies have also indicated that severity of psychopathology is further exacerbated in children with both epilepsy and mental retardation (Caplan and Austin, 2000). Underlying brain abnormalities are often associated with impaired cognitive functions in children with epilepsy (Kobayashi, Ohtsuka, Ohno, Tanaka, Hiraki and Oka, 2001; Nolan et al., 2003). Children with symptomatic epilepsy are more likely have mental retardation (Vasconcellos et al., 2001). In population based studies, about 20–40 % of children with epilepsy are reported to have mental retardation (Camfield and Camfield, 2007; Eriksson and Koivikko, 1997; Sidenvall, Forsgren and Heijbel, 1996; Sillanpää, 1992; Waaler, Blom, Skeidsvoll and Mykletun, 2000). However, cognitive functions in children with idiopathic or uncomplicated epilepsy are mostly within normal range (see for example, Elger et al., 2004; Motamedi and
214
K. Rantanen, K. Eriksson and P. Nieminen
Meador, 2003), although sometimes differing from healthy controls (e.g. Cormack et al., 2007; Høie, Mykletun, Sommerfelt, Bjørnæs, Skeidsvoll and Waaler, 2005). Other epilepsy related factors possibly associating with social competence include age at onset of seizures. Children with early onset epilepsy are at risk of behavioral problems and/or impaired social competence during their preschool years (Rantanen et al., 2009). Also, recurrent seizures and high seizure frequency are associated with behavior problems (Austin et al., 2002). It has been proposed that intractable seizures (i.e. uncontrolled) account for a significant portion of the variance in behavioral problems (Austin et al., 2001; Dunn, Austin and Huster, 1997). Especially, seizure frequency in the past year predicts behavioral problems (Schoenfeld et al., 1999). On the other hand, recurrent seizures predict behavior problems very early in the course of epilepsy (Austin et al., 2002). It is possible such seizures disrupt behavior or that children have negative psychological reactions to seizure activity (Austin et al., 2002). Behavioral problems may have already occurred in the earliest stage of the disease (Oostrom et al., 2003a). Or it is possible that children with prior unrecognized seizures may be at increased risk for behavior problems (Dunn, Harezlak, Ambrosius, Austin and Hale, 2002). Some of the epilepsy related factors may possibly interfere with the achievement of social competence (Kirsch, 2006). Although some (e.g. Høie et al., 2005) have found an association between psychosocial problems and epilepsy related variables, the majority of studies do not demonstrate any such correlation between seizure related variables (e.g. age at onset, epilepsy syndrome, seizure frequency and seizure type) and lower social competence scores (e.g. Caplan et al., 2005; Plioplys et al., 2007). Hence, some controversy exists whether it is the seizure related variables that affect or contribute to behavior problems, since they do not necessarily predict lower social competence (Caplan et al., 2004; Keene et al., 2005). Plioplys et al. (2007) suggested on the basis of their review that in cognitively normal children with epilepsy (i.e. children with uncomplicated epilepsy) epilepsy related variables seem to relate inconsistently to psychopathology. Rather, they suggested that lower social competence was more related to cognitive and family variables. Instead, cognitive problems or developmental delay, hyperactivity and autistic problems seemed to be more associated with children with symptomatic or complicated epilepsy or epilepsy syndromes (Plioplys et al., 2007).
Neurocognitive Impairments and Social Competence Possibly, seizures, cognitive impairment and lower social competence are caused by the same underlying neurological disorder (Dunn et al., 1997; Keene et al., 2005; Noeker et al., 2005). Due to strong associations between underlying CNS dysfunction and cognitive function, the development of social competence may be mediated or moderated through cognitive factors rather than epilepsy related factors. Behavior problems are typically more prevalent in those children with both epilepsy and intellectual or neurocognitive disabilities (Buelow, Austin, Perkins, Shen, Dunn and Fastenau, 2003; Caplan and Austin, 2000; Keene et al., 2005; Rantanen et al., 2009). But, cognitive impairment may, at least partly, be regarded as an independent factor contributing to social competence. A child with problems
Social Competence and Children with Epilepsy
215
in basic cognitive skills is also more likely to have problems with social skills, hence social competence. There is for instance a subgroup with symptomatic or complicated epilepsy that has impaired cognitive functions and poorer social skills (Rantanen et al., 2009). In addition to impaired cognitive function or mental retardation, various specific neurocognitive deficits have been reported in children with idiopathic epilepsies. There is no typical pattern of neuropsychological impairment in idiopathic epilepsy (Deonna, Zesiger, Davidoff, Maeder and Roulet, 2000; Seidenberg, 1989) or in childhood epilepsy in general (Williams, Griebel and Dykman, 1998). Instead, a more diffuse neuropsychological profile with uncomplicated childhood epilepsy (Germanó et al., 2005; Williams et al., 1998) has been proposed. Neurocognitive variables can predict lower social competence scores and even the presence of psychiatric diagnosis predictors which may include impaired attention skills (Plioplys et al., 2007), social communication (Caplan et al., 2005) and verbal intelligence (Caplan et al., 2004). Studies have shown that attention problems in particular are characteristic of children with epilepsy (Plioplys et al., 2007; Rodenburg et al., 2005b). Attention problems are frequently reported in children with neurocognitive problems and also in school-aged children with idiopathic or uncomplicated epilepsy (for example, Henkin, Sadeh, Kivity, Shabtai, Kishon-Rabin and Gadoth, 2005; Oostrom, Teeseling, Smeets-Schouten, Peters and Jennekens-Schinkel, 2005; Williams et al., 1998). Attention problems include both inattentive type (Dunn and Kronenberger, 2005) and impulsive type, i.e. attention-deficit-hyperactivity disorder (ADHD) (Leonard and George, 1999; Williams, Schulz and Griebel, 2001). However, Dunn et al. (2003) have demonstrated that children with epilepsy differ from other samples of children with ADHD by the higher proportion of ADHD-inattentive type. Attention deficits may be one of the significant moderators for developing problems in social competence. Studies in typically developing children and children with attention deficits have shown that particularly impulsive behavior and hyperactivity are related to behavioral and social problems (e.g. Guevremont and Dumas, 1994; Landau and Moore, 1991). Children with inattention problems have also been found to display socially passive behaviors, and deficits in social knowledge (i.e. basic skills), but not in emotion regulation as do children with hyperactive problems (Maedgen and Carlson, 2000). Generally, inattentive behavior is associated with adjustment problems and lower self-esteem (Warner-Rogers, Taylor, Taylor and Sandberg, 2000). It is possible that children with epilepsy who lack the age-appropriate social skills and who have attention problems may be further predispose to behavioral problems (Rantanen et al., 2009).
Family Factors and Social Competence Recent studies have emphasized the importance of family functioning or family dysfunction in childhood epilepsy. Studies have shown that in addition to cognitive deficits, family factors may have a moderating effect on psychopathology (Plioplys et al., 2007; Rodenburg et al., 2005a). Epilepsy may have an immediate and significant impact on the family, which in turn may lead to changes in family dynamics. Epilepsy may become the focus of the parents‘ attention, for example parental anxiety towards epilepsy and recurring seizures may have an effect on social competence and adjustment. Williams et al. (2003) have
216
K. Rantanen, K. Eriksson and P. Nieminen
demonstrated that parental anxiety was indeed one of the significant factors associated with overall quality of life for children with epilepsy. In particular, maternal anxiety about epilepsy may be associated with overprotective and overly directive parenting styles, as shown by Chapieski et al. (2005). In addition to parental anxiety, other family related factors, such as disorganized or unsupportive home environments (Austin, Risinger and Beckett, 1992; Rodenburg et al., 2005a; Thome-Souza et al., 2004) have been found to further affect neuropsychological and behavioral deficits in children with epilepsy. An association between a child‘s early temperament, family environment and behavioral problems has been established. Family adaptive resources have been found to be of importance by moderating the relationship between temperament and behavior problems (Baum et al., 2007). In their recent study Baum et al. (2007) demonstrated in children with new-onset seizures that difficult temperament and resistance to control correlated with behavioral problems, both internalizing and externalizing problems. Also, temperament dimensions of unadaptability were associated with internalizing problems. It is noteworthy, that family adaptive resources moderated the temperament of the relationships and the behavioral problems at school. Baum et al. (2007) concluded that low family mastery of children with difficult temperaments is a risk factor for behavioral problems. Whether the behavioral problems are primarily attributed to epilepsy, especially to seizure frequency or to cognitive problems, like attention problems and family dysfunction, remains inconclusive. It is also possible that family and environmental factors may be of greater importance in the maintenance of behavioral problems and lower social competence.
Protective Factors for Social Competence There is a solid body of studies demonstrating the risk factors and contributing factors for lower social competence in children with epilepsy. Despite the fact that some of these factors, e.g. intelligence and communication skills may be impaired in children with epilepsy, several protective factors are important for the development of social competence. Much less focus has been paid to resilience factors in studies. In clinical practice we do know that some children seem to be quite resilient and able to achieve positive outcomes despite the severity or intractability of epilepsy. In general, individual protective factors for typically developing children include temperament, intelligence and scholastic competence, effective communication and problem solving skills. Also positive self-esteem and high self-efficacy and, at the family level, protective factors include healthy relationships and positive parenting (see Mash and Wolfe, 1999). Epilepsy is characteristically a chronic condition with limitations and restrictions of participation. The children‘s social environment may be restricted and their social network altered due to epilepsy related factors. Most of the restrictions are related to re-occurring seizures in order to increase safety. Children and adolescents with epilepsy are often concerned and distressed about daily life restrictions and loss of independence (Ronen, Rosenbaum, Law and Streiner, 1999; 2001). Despite good seizure control, children may experience insecurity and fear of seizures. Unpredictable seizures may be one of the greatest fears in children and teens with epilepsy. Children and adolescents with epilepsy have a
Social Competence and Children with Epilepsy
217
strong drive for normalcy, and perceive seizures as the major barrier to their sense of normalcy (Elliott, Lach and Smith, 2005). Promoting children‘s social participation and peer relations are important because friends play an important role in facilitating psychosocial adaptation with epilepsy (La Greca, Bearman and Moore, 2002). The ability to maintain mutual friendships is an important factor in children‘s social development even in preschool years (Lindsey, 2002). Close friendships may function as protective factors against mental and/or behavioral problems. Social support provided by friends may facilitate illness adaptation and promote health-promoting behaviors in children with epilepsy (La Greca et al., 2002). At best, older children and teens (over 13 years of age) with epilepsy have reported supportive and positive relationships with families and close friends (Wilde and Haslam, 1996). There are some qualitative studies that focus on childhood or adolescent perceptions and their experiences of life with epilepsy (Elliott, Lach and Smith, 2000; 2005; McEwan, Espie, Metcalfe, Brodie and Wilson, 2004). Studies have shown that the children consider their epilepsy to have had a great physical and social impact (Cheung and Wirrell, 2006). Children with epilepsy have reported worries concerning how they are perceived and treated by their peers (Ronen et al., 1999). For example, there is some evidence that some children may be reluctant to befriend peers with epilepsy, and that children and adolescents with epilepsy are more likely to be bullied (e.g. Hamiwka, Yu, Hamiwka, Sherman and Anderson, 2009). Particularly, adolescents with visible epilepsy have reported greater perceived loneliness, although fewer problems with adjustment (Curtin and Siegel, 2003). Also, concerns about life-style, school and later driving are frequent (Fisher et al., 2000). In order to promote peer relations, normal, age-appropriate physical and social participation should be encouraged in children with epilepsy. Children and adolescents with epilepsy are found to participate less in group or sporting activities than their siblings or peers (Wong and Wirrell, 2006). But it should be noted that epilepsy related variables; with the exception of seizure frequency, were not associated with this non-participation. Instead, Wong and Wirrell (2006) have found a tendency to withdraw from social activities in children with epilepsy. Support of healthy peer relationships is also important for the development of self-image and self-esteem. There is evidence that epilepsy may affect the development of childhood self-image/conception, identity and independency (McEwan et al., 2004). This may be partly due to restrictions associated with epilepsy. In addition to behavior problems, adolescents with epilepsy are at risk of lower self-esteem, loneliness and anxiety (Leonard and George, 1999). Although, some improvements in public attitudes towards epilepsy have been demonstrated, old ideas or attitudes toward epilepsy continue resulting in a difficult social environment for those children and families with epilepsy (Jacoby and Austin, 2007). Cheung and Wirrell (2006) have studied perceptions of physical and social impact of chronic illness. They found that a more negative social impact was still associated with epilepsy than with asthma, diabetes or migraine. In particular, negative impact was related to behavior, honesty, popularity, adeptness at sports and fun. More positive attitudes may help to improve problems with poor self-concept or behavior problems, although they might not influence social competence (Funderburk, McCormick and Austin, 2007). Scambler and Hopkins (1986) classified stigma into enacted and felt sigma. Enacted stigma refers to legitimated discrimination or restrictions as a consequence of epilepsy. Felt stigma is more complicated to define but relates to fear of discrimination and feelings of shame of being ‗epileptic‘. Due to
218
K. Rantanen, K. Eriksson and P. Nieminen
felt stigma, persons with epilepsy try to hide their illness whenever possible. Therefore, felt stigma is usually more restrictive than public, enacted stigma (Scambler, 1984).
Conclusions In this chapter, we have reviewed current knowledge of social competence in the context of childhood epilepsy. Epilepsy is a pervasive condition that associates seizures with cognitive and behavioral problems. Several studies have reported behavioral and psychiatric problems in children with epilepsy. Although risk factors for behavior problems and psychopathology have been identified in children with epilepsy, knowledge of the interaction and mechanism of these factors and development of behavior problems is lacking. The effects of epilepsy on social competence and overall mental health may be indirect rather than direct (Noeker et al., 2005). Rodenburg et al. (2005b) suggested focusing on a multifactorial framework where both neurological and psychosocial factors are considered. Also, Noeker et al. (2005) proposed a conceptual framework of the possible causes, moderators and mediators of mental health outcome in children with epilepsy. Several risk factors, some relating to epilepsy, neuro-cognitive impairment and family functioning in children with epilepsy have been demonstrated. However, there is still a lack of knowledge on the pathways of epilepsy related risk-factors and development of mental health dysfunction, or weaker social competence. It is possible that the behavioral problems found in children with epilepsy are mainly related to overall cognitive capacity and specific neuro-cognitive impairments (e.g. attention). Although there may be an underlying neurological cause for lowered social competence demonstrated as behavior problems, it is possible that the lack of age-appropriate social skills or socio-cognitive skills predisposes children to behavioral problems. The risk of developing problems in social competence seems to increase especially if attention problems, both impulsive and inattentive behavior, are evident. In addition, problems in parenting may further increase the occurrence of difficulties in social competence. One possibility, as Rodenburg et al. (2005b) concluded based on their meta-analysis, is that some of the problems found in children with epilepsy may, at least partly, be associated with chronic illness in general, not specifically with epilepsy. Similarly, Plioplys et al. (2007) concluded that instead of seizure related variables non-epilepsy related variables may contribute more to mental health problems. For long-term outcomes, follow-up studies have also emphasized the predictive value of psychological and cognitive impairments instead of seizure-related variables (Sillanpää, Jalava, Kaleva and Shinnar, 1998). The earlier studies conducted on social competence in children with epilepsy have some limitations. The majority of studies have concentrated on the psychiatric aspects of behavior. Studies conducted on social skills and competence, e.g. mastering of age-appropriate social skills and peer relations rather than psychopathology are mostly lacking. Nevertheless, behavioral problems or antisocial behavior is just one aspect of social competence. By definition, the concept of social competence also refers to mastering social skills, to the individual ability to function in age-appropriate social contexts, and to adapt to different social demands. Yet, there are only a few studies focusing on social skills and peer relations. In a recent study, Tse, Hamiwka, Shermann and Wirrell (2007) focus on the social skills of children with epilepsy. They found that children with epilepsy had indeed poorer social skills
Social Competence and Children with Epilepsy
219
and were less assertive than their siblings. Also, Rantanen et al (2009) demonstrated lower social skills than healthy peers. However, both of these studies concluded that lower social skills were associated more with complicated epilepsy i.e. children with symptomatic epilepsy or with additional neurologic impairments. Drewel, Bell and Austin (2009) recently showed that in typically developing children peer difficulties were related to inattention and anxious behaviors. In addition, some epilepsy related variables (i.e. age at onset and active seizures) were found to be associated with peer problems. Still, further studies are needed to gain greater insight into the developmental course of the social competence of children with epilepsy. In future studies and also in clinical practice social skills and adaptive behavior, as opposed to psychopathology, should be emphasized as important subcomponents of social competence (Tse et al., 2007). Buelow et al. (2003) suggested that children with epilepsy and low cognitive capacity should be carefully assessed for behavioral and mental health problems. Further studies on the social skills and the development of children with epilepsy are needed to increase our understanding of the possible developmental pathways to lowered social competence and to psychiatric problems in children with epilepsy. This would also be beneficial regarding early intervention. Also for professionals, preferably for a multiprofessional team, it is important to evaluate these issues associated with social competence for identification of child needs and treatment planning. In clinical practice and epilepsy guidance, attention should be paid to the development of social skills and behavior of these children with epilepsy in order to support acquisition of age appropriate social skills and overall psychosocial development. Especially, preschool-age represents on individual level a period of rapid cognitive and social development, which in turn is a basis for the subsequent development of academic skills and prosocial behavior during school age. Developmental, social and behavioral problems in this age range may have long-lasting effects in later development and therefore the clinical implications of the studies rewieved here are important. Therefore, it is of importance that these possible risk factors are recognized. Social and behavioral issues should be considered individually for each child. The fact that epilepsy is a heterogeneous condition should be taken into consideration, although for many children, seizures are well-controlled with modern anticonvulsants. Behavioral and social issues are of special importance for those children with refractory epilepsy and additional cognitive problems. The issues relating to social competence and protective factors in children with epilepsy discussed in this chapter may also be viewed against the model of International Classification of Functioning, Disability and Health, ICF, (WHO, 2001). In addition to functioning and disability, the ICF model emphasizes activity, participation and possible activity limitations and participation restrictions. Contextual factors, like facilitators or barriers are also considered in the model. These issues related to participation and restrictions are often familiar to children with epilepsy. It is of importance that parents have a realistic understanding of the condition and its consequences, including possible restrictions of participation. In particular, avoidance of unnecessary and unwarranted restrictions on everyday life should be emphasized. Parents may also need some guidance so that they can differentiate inappropriate behavior and pose age-appropriate demands and goals. Also, in clinical practice we should concentrate more on social skills and support the mastering of ageappropriate social competence. In addition, children and families would benefit from positive reinforcement as opposed to diagnosing comorbid behavior problems.
220
K. Rantanen, K. Eriksson and P. Nieminen
To conclude, factors contributing to or associated with social competence in children with epilepsy are multi-factorial in nature. There are mediators or possible predictors to be considered of which some are more related to seizures and their etiology per se, but most important moderators seem to be related to cognitive, family and environmental factors. Firstly, the findings reviewed in this chapter emphasized the need for further studies on social competence in children with epilepsy. Secondly, the importance of early assessment and appropriate interventions are highlighted.
References Achenbach, T., M. (1991). Manual for the Child Behavior Checklist / 4-18 and 1991 profile. Burlington, VT: University of Vermont Department of Psychiatry. Achenbach, T., M. (1992). Manual for the Child Behavior Checklist / 2-3 and 1992 profile. Burlington, VT: University of Vermont Department of Psychiatry. Austin, J. K., and Caplan, R. (2007). Behavioral and psychiatric comorbidities in pediatric epilepsy: Toward an integrative model. Epilepsia, 48(9), 1639-1651. Austin, J. K., Dunn, D. W., Caffrey, H. M., Perkins, S. M., Harezlak, J., and Rose, D. F. (2002). Recurrent seizures and behavior problems in children with first recognized seizures: A prospective study. Epilepsia, 43(12), 1564-1573. Austin, J. K., Harezlak, J., Dunn, D. W., Huster, G. A., Rose, D. F., and Ambrosius, W. T. (2001). Behavior problems in children before first recognized seizures. Pediatrics, 107(1), 115-122. Austin, J. K., Risinger, M. W., and Beckett, L. A. (1992). Correlates of behavior problems in children with epilepsy. Epilepsia, 33(6), 1115-1122. Baum, K. T., Byars, A. W., deGrauw, T. J., Johnson, C. S., Perkins, S. M., Dunn, D. W., et al. (2007). Temperament, family environment, and behavior problems in children with newonset seizures. Epilepsy and Behavior, 10(2), 319-327. Berg, A. T., Smith, S. N., Frobish, D., Beckerman, B., Levy, S. R., Testa, F. M., et al. (2004). Longitudinal assessment of adaptive behavior in infants and young children with newly diagnosed epilepsy: Influences of etiology, syndrome, and seizure control. Pediatrics, 114(3), 645-650. Buelow, J. M., Austin, J. K., Perkins, S. M., Shen, J., Dunn, D. W., and Fastenau, P. S. (2003). Behavior and mental health problems in children with epilepsy and low IQ. Developmental Medicine and Child Neurology, 45(10), 683-692. Camfield, C., and Camfield, P. (2007). Preventable and unpreventable causes of childhoodonset epilepsy plus mental retardation. Pediatrics, 120(1), e52-55. Caplan, R., and Austin, J. K. (2000). Behavioral aspects of epilepsy in children with mental retardation. Mental Retardation and Developmental Disabilities Research Reviews, 6(4), 293-299. Caplan, R., Guthrie, D., Komo, S., Siddarth, P., Chayasirisobhon, S., Kornblum, H., et al. (2002). Social communication in children with epilepsy. Journal of Child Psychology and Psychiatry, 43(2), 245-253.
Social Competence and Children with Epilepsy
221
Caplan, R., Sagun, J., Siddarth, P., Gurbani, S., Koh, S., Gowrinathan, R., et al. (2005). Social competence in pediatric epilepsy: Insights into underlying mechanisms. Epilepsy and Behavior, 6(2), 218-228. Caplan, R., Siddarth, P., Gurbani, S., Ott, D., Sankar, R., and Shields, W. D. (2004). Psychopathology and pediatric complex partial seizures: Seizure-related, cognitive, and linguistic variables. Epilepsia, 45(10), 1273-1281. Cavell, T. A. (1990). Social adjustment, social performance, and social skills: A tricomponent model of social competence. Journal of Clinical Child Psychology, 19(2), 111-122. Chapieski, L., Brewer, V., Evankovich, K., Culhane-Shelburne, K., Zelman, K., and Alexander, A. (2005). Adaptive functioning in children with seizures: Impact of maternal anxiety about epilepsy. Epilepsy and Behavior, 7(2), 246-252. Cheung, C., and Wirrell, E. (2006). Adolescents' perception of epilepsy compared with other chronic diseases: "Through a teenager's eyes". Journal of Child Neurology, 21(3), 214222. Conners, C. K. (1997). Conners' Rating Scales - Revised. North Tonawanda: Multi-Health Systems, Inc. Cormack, F., Cross, J. H., Isaacs, E., Harkness, W., Wright, I., Vargha-Khadem, F., et al. (2007). The development of intellectual abilities in pediatric temporal lobe epilepsy. Epilepsia, 48(1), 201-204. Curtin, L. S., and Siegel, A. W. (2003). Social functioning in adolescents with epilepsy. Children's Health Care, 32(2), 103-114. Davies, S., Heyman, I., and Goodman, R. (2003). A population survey of mental health problems in children with epilepsy. Developmental Medicine and Child Neurology, 45(5), 292-295. Denham, S. A., Blair, K. A., DeMulder, E., Levitas, J., Sawyer, K., Auerbach-Major, S., et al. (2003). Preschool emotional competence: Pathway to social competence? Child Development, 74(1), 238-256. Deonna, T., Zesiger, P., Davidoff, V., Maeder, M., and Roulet, E. (2000). Benign partial epilepsy of childhood: Alongitudinal neuropsychological and EEG study of cognitive function. Develomental Medicine and Child Neurology, 42, 595-603. Diener, M. L., and Kim, D.-Y. Maternal and child predictors of preschool children's social competence. Journal of Applied Developmental Psychology, 25(1), 3-24. Dodge, K. A., and Feldman, E. (1990). Issues in social cognition and sociometric status. In S. R. Asher and J. D. Coie (Eds.), Peer rejection in childhood (pp. 119-155). Cambridge, UK: Cambridge University Press. Doll, E. A. (1965 / 1977). Vineland social maturity scale (Finnish version). Helsinki: Psykologien Kustannus. Drewel, E. H., Bell, D. J., and Austin, J. K. (2009). Peer difficulties in children with epilepsy: Association with seizure, neuropsychological, academic, and behavioral variables. Child Neuropsychology, 15(4), 305-320. Dunn, D. W. (2003). Neuropsychiatric aspects of epilepsy in children. Epilepsy and Behavior, 4(2), 101-106. Dunn, D. W., and Austin, J. K. (1999). Behavioral issues in pediatric epilepsy. Neurology, 53(5), S96-100.
222
K. Rantanen, K. Eriksson and P. Nieminen
Dunn, D. W., Austin, J. K., Harezlak, J., and Ambrosius, W. T. (2003). ADHD and epilepsy in childhood. Developmental Medicine and Child Neurology, 45(1), 50-54. Dunn, D. W., Austin, J. K., and Huster, G. A. (1997). Behaviour problems in children with new-onset epilepsy. Seizure, 6(4), 283-287. Dunn, D. W., Harezlak, J., Ambrosius, W. T., Austin, J. K., and Hale, B. (2002). Teacher assessment of behaviour in children with new-onset seizures. Seizure, 11(3), 169-175. Dunn, D. W., and Kronenberger, W. G. (2005). Childhood epilepsy, attention problems, and adhd: Review and practical considerations. Seminars in Pediatric Neurology, 12(4), 222228. Elger, C. E., Helmstaedter, C., and Kurthen, M. (2004). Chronic epilepsy and cognition. The Lancet Neurology, 3(11), 663-672. Elliott, I. M., Lach, L., and Smith, M. L. (2000). Adolescent and maternal perspectives of quality of life and neuropsychological status following epilepsy surgery. Epilepsy and Behavior, 1(6), 406-417. Elliott, I. M., Lach, L., and Smith, M. L. (2005). I just want to be normal: A qualitative study exploring how children and adolescents view the impact of intractable epilepsy on their quality of life. Epilepsy and Behavior, 7(4), 664-678. Engel, J. (2001). A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: Report of the ilae task force on classification and terminology. Epilepsia (Series 4), 42(6), 796-803. Engel, J. J. (2006). ILAE classification of epilepsy syndromes. Epilepsy Research, 70 (Suppl. 1), 5-10. Fabes, R. A., and Eisenberg, N. (1999). Regulation, emotionality, and preschoolers' socially competent peer interactions. Child Development, 70(2), 432-442. Fisher, R. S., Vickrey, B. G., Gibson, P., Hermann, B., Penovich, P., Scherer, A., et al. (2000). The impact of epilepsy from the patient's perspective I. Descriptions and subjective perceptions. Epilepsy Research, 41(1), 39-51. Funderburk, J. A., McCormick, B. P., and Austin, J. K. (2007). Does attitude toward epilepsy mediate the relationship between perceived stigma and mental health outcomes in children with epilepsy? Epilepsy and Behavior, 11(1), 71-76. Germanó, E., Gagliano, A., Magazú, A., Sferro, C., Calarese, T., Mannarino, E., et al. (2005). Benign childhood epilepsy with occipital paroxysms: Neuropsychological findings. Epilepsy Research, 64(3), 137-150. Guevremont, D. C. and Dumas, M. C. (1994). Peer relationship problems and disruptive behavior disorders. Journal of Emotional and Behavioral Disorders, 2 (3), 164-172. Goodman, R. (1997). The strength and difficulties questionnaire: A research note. Journal of Child Psychology and Psychiatry, 38, 581–586. Gresham, F. M. (1986). Conceptual issues in the assessment of social competence in children. In P. S. Strain, M. J. Guralnick and H. M. Walker (Eds.), Childrens' social behavior. Development, assessment and modification. (pp. 143-179). Orlando, Florida: Academic Press Inc. Gresham, F. M., and Elliot, S. N. (1987). The relationship between adaptive behavior and social skills: Issues in definition and assessment. Journal of Special Education, 21(1), 167-181. Gresham, F. M., and Elliot, S. N. (1990). Social Skills Rating System manual. Circle Pines, MN: American Quidance System.
Social Competence and Children with Epilepsy
223
Hamiwka, L. D., Yu, C. G., Hamiwka, L. A., Sherman, E. M. S., and Anderson, B. (2009). Are children with epilepsy at greater risk for bullying than their peers? Epilepsy and Behavior, 15, 500-505. Henkin, Y., Sadeh, M., Kivity, S., Shabtai, E., Kishon-Rabin, L., and Gadoth, N. (2005). Cognitive function in idiopathic generalized epilepsy of childhood. Developmental Medicine and Child Neurology, 47(2), 126-132. Høie, B., Mykletun, A., Sommerfelt, K., Bjørnæs, H., Skeidsvoll, H., and Waaler, P. E. (2005). Seizure-related factors and non-verbal intelligence in children with epilepsy: A population-based study from western Norway. Seizure, 14(4), 223-231. Hommet, C., Sauerwein, H. C., De Toffol, B., and Lassonde, M. (2006). Idiopathic epileptic syndromes and cognition. Neuroscience and Biobehavioral Reviews, 30, 85-96. Jacoby, A., and Austin, J. K. (2007). Social stigma for adults and children with epilepsy. Epilepsia, 48 Suppl 9, 6-9. Jakovljevic, V., and Martinovic, Z. (2006). Social competence of children and adolescents with epilepsy. Seizure, 15(7), 528-532. John, K. (2001). Measuring children's social functioning. Child and Adolescent Mental Health, 6(4), 181-188. Junttila, N., Voeten, M., Kaukiainen, A., and Vauras, M. (2006). Multisource assessment of children's social competence. Educational and Psychological Measurement, 66(5), 874895. Kaufman, J., and Birmaher, B. (1997). Schedule for affective disorders and schizophrenia for school-age children-present and lifetime. Journal of the American Academy of Child and Adolescent Psychiatry, 36(7), 980-988. Kavale, K. A., and Forness, S. R. (1996). Social skill deficits and learning disabilities: A meta-analysis. Journal of Learning Disabilities, 29(3), 226-237. Keene, D. L., Manion, I., Whiting, S., Belanger, E., Brennan, R., Jacob, P., et al. (2005). A survey of behavior problems in children with epilepsy. Epilepsy and Behavior, 6(4), 581586. Kirsch, H. E. (2006). Social cognition and epilepsy surgery. Epilepsy and Behavior, 8(1), 7180. Kobayashi, K., Ohtsuka, Y., Ohno, S., Tanaka, A., Hiraki, Y., and Oka, E. (2001). Agerelated clinical and neurophysiologic characteristics of intractable epilepsy associated with cortical malformation. Epilepsia, 42 Suppl 6, 24-28. Eriksson, K. J., and Koivikko, M. J. (1997). Prevalence, classification, and severity of epilepsy and epileptic syndromes in children. Epilepsia, 38(12), 1275-1282. La Greca, A. M., Bearman, K. J., and Moore, H. (2002). Peer relations of youth with pediatric conditions and health risks: Promoting social support and healthy lifestyles. Developmental and behavioral pediatrics, 23(4), 271-280. Ladd, G. W. (1999). Peer relationships and social competence during early and middle childhood. Annual Review of Psychology, 50(1), 333-359. Landau, S. and Moore, L. A. (1991). Social skills deficits in children with attention-deficit hyperactivity disorder. School Psychology Review, 20 (2), 235-251. Leonard, E. L., and George, M. R. M. (1999). Psychosocial and neuropsychological function in children with epilepsy. Pediatric Rehabilitation, 3(3), 73-80. Lindsey, E. W. (2002). Preschool children's friendships and peer acceptance: Links to social competence. Child Study Journal, 32(3), 145-156.
224
K. Rantanen, K. Eriksson and P. Nieminen
Maedgen, J. W., and Carlson, C. L. (2000). Social functioning and emotional regulation in the attention deficit hyperactivity disorder. Journal of Clinical Child Psychology, 29(1), 3042. Malone, D. (2007). Mothers' perceptions regarding the social competence of preschool children with mental retardation. Journal of Developmental and Physical Disabilities, 19(4), 365-383. Mandelbaum, D. E., and Burack, G. D. (1997). The effect of seizure type and medication on cognitive and behavioral functioning in children with idiopathic epilepsy. Developmental Medicine and Child Neurology, 39, 731-735. Mash, E. J., and Wolfe, D. A. (1999). Abnormal child psychology. Belmont, CA: Wadsworth. Masten, A. S., and Coatsworth, J. D. (1998). The development of compentence in favorable and unfavorable environments: Lessons from research on successful children. American Psychologist, 53, 205-220. McCabe, P. C., and Meller, P. J. (2004). The relationship between language and social competence: How language impairment affects social growth. Psychology in the Schools, 41(3), 313-322. McDermott, S., Mani, S., and Krishnawami, S. (1995). A population-based analysis of specific behavior problems associated with childhood seizures. Journal of Epilepsy, 8(2), 110-118. McEwan, M. J., Espie, C. A., Metcalfe, J., Brodie, M. J., and Wilson, M. T. (2004). Quality of life and psychosocial development in adolescents with epilepsy: A qualitative investigation using focus group methods. Seizure, 13(1), 15-31. Motamedi, G., and Meador, K. (2003). Epilepsy and cognition. Epilepsy and Behavior, 4, S25-S38. Nassau, J. H., and Drotar, D. (1997). Social competence among children with central nervous system-related chronic health conditions: A review. Journal of Pediatric Psychology, 22(6), 771-793. Noeker, M., Haverkamp-Krois, A., and Haverkamp, F. (2005). Development of mental health dysfunction in childhood epilepsy. Brain and Development, 27(1), 5-16. Nolan, M. A., Redoblado, M. A., Lah, S., Sabaz, M., Lawson, J. A., Cunningham, A. M., et al. (2003). Intelligence in childhood epilepsy syndromes. Epilepsy Research, 53(1/2), 139-150. Oostrom, K. J., Schouten, A., Kruitwagen, C. L. J. J., Peters, A. C. B., and JennekensSchinkel, A. (2003a). Behavioral problems in children with newly diagnosed idiopathic or cryptogenic epilepsy attending normal schools are in majority not persistent. Epilepsia, 44(1), 97-106. Oostrom, K. J., Smeets-Schouten, A., Kruitwagen, C. L. J. J., Peters, A. C. B., and JennekensSchinkel, A. (2003b). Not only a matter of epilepsy: Early problems of cognition and behavior in children with "epilepsy only"-a prospective, longitudinal, controlled study starting at diagnosis. Pediatrics, 112(6), 1338-1344. Oostrom, K. J., Teeseling, v. H., Smeets-Schouten, A., Peters, A. C. B., and JennekensSchinkel, A. (2005). Three to four years after diagnosis: Cognition and behaviour in children with "epilepsy only". A prospective, controlled study. Brain: A Journal of Neurology, 128(7), 1546-1555.
Social Competence and Children with Epilepsy
225
Ott, D., Siddarth, P., Gurbani, S., Koh, S., Tournay, A., Shields, W. D., et al. (2003). Behavioral disorders in pediatric epilepsy: Unmet psychiatric need. Epilepsia, 44(4), 591597. Plioplys, S., Dunn, D. W., and Caplan, R. (2007). 10-year research update review: Psychiatric problems in children with epilepsy. Journal of the American Academy of Child and Adolescent Psychiatry, 46(11), 1389-1402. Rantanen, K., Timonen, S., Hagström, K., Hämäläinen, P., Eriksson, K., and Nieminen, P. (2009). Social competence of preschool children with epilepsy. Epilepsy and Behavior, 14, 338-343. Rodenburg, R., Meijer, A. M., Dekovic, M., and Aldenkamp, A. P. (2005a). Family factors and psychopathology in children with epilepsy: A literature review. Epilepsy and Behavior, 6(4), 488-503. Rodenburg, R., Stams, G. J., Meijer, A. M., Aldenkamp, A. P., and Dekovic, M. (2005b). Psychopathology in children with epilepsy: A meta-analysis. J. Pediatr. Psychol., 30(6), 453-468. Ronen, G. M., Rosenbaum, P., Law, M., and Streiner, D. L. (1999). Health-related quality of life in childhood epilepsy: The results of children's participation in identifying the components. Developmental Medicine and Child Neurology, 41(8), 554-559. Ronen, G. M., Rosenbaum, P., Law, M., and Streiner, D. L. (2001). Health-related quality of life in childhood disorders: A modified focus group technique to involve children. Quality of Life Research, 10(1), 71-79. Rose-Krasnor, L. (1997). The nature of social competence: A theoretical review. Social Development, 6(1), 111-135. Scambler, G. (1984). Percieving and coping with stigmatizing illness. In R. Fitzpatrick, J. Hinton, G. Scambler and J. Thompson (Eds.), The experience of illness (pp. 203–226). London: Tavistock Publications. Scambler, G., and Hopkins, A. (1986). Being epileptic: Coming to terms with stigma. Sociology of health and illness. Journal of Medical Sociology, 8(1), 26-43. Schoenfeld, J., Seidenberg, M., Woodard, A., Hecox, K., Inglese, C., Mack, K., et al. (1999). Neuropsychological and behavioral status of children with complex partial seizures. Developmental Medicine and Child Neurology, 41(11), 724-731. Seidenberg, M. (1989). Neuropsychological functioning of children with epilepsy. In B. P. Hermann and M. Seidenberg (Eds.), Childhood epilepsies: Neuropsychological, psychosocial and intervention aspects (pp. 71-81). Chichester: John Wiley and Sons. Sidenvall, R., Forsgren, L., and Heijbel, J. (1996). Prevalence and characteristics of epilepsy in children in northern Sweden. Seizure, 5(2), 139-146. Sillanpää, M. (1992). Epilepsy in children: Prevalence, disability, and handicap. Epilepsia, 33(3), 444-449. Sillanpää, M., Jalava, M., Kaleva, O., and Shinnar, S. (1998). Long-term prognosis of seizures with onset in childhood. New England Journal of Medicine, 338(24), 1715-1722. Sparrow, S. S., Balla, D. A., and Cicchetti, D. V. (1984). Vineland Adaptive Behavior Scales: American Guidance Service. Thome-Souza, S., Kuczynski, E., Assumpcao, F., Rzezak, P., Fuentes, D., Fiore, L., et al. (2004). Which factors may play a pivotal role on determining the type of psychiatric disorder in children and adolescents with epilepsy? Epilepsy and Behavior, 5(6), 988994.
226
K. Rantanen, K. Eriksson and P. Nieminen
Tse, E., Hamiwka, L., Sherman, E. M. S., and Wirrell, E. (2007). Social skills problems in children with epilepsy: Prevalence, nature and predictors. Epilepsy and Behavior, 11(4), 499-505. Waaler, P. E., Blom, B. H., Skeidsvoll, H., and Mykletun, A. (2000). Prevalence, classification, and severity of epilepsy in children in western Norway. Epilepsia, 41(7), 802-810. Warner-Rogers, J., Taylor, A., Taylor, E., and Sandberg, S. (2000). Inattentive behavior in childhood. Journal of Learning Disabilities, 33(6), 520-536. Vasconcellos, E., Wyllie, E., Sullivan, S., Stanford, L., Bulacio, J., Kotagal, P., et al. (2001). Mental retardation in pediatric candidates for epilepsy surgery: The role of early seizureandnbsp;onset. Epilepsia, 42(2), 268-274. Wilde, M., and Haslam, C. (1996). Living with epilepsy: A qualitative study investigating the experiences of young people attending outpatient clinics in Leicester. Seizure, 5, 63-72. Williams, J., Griebel, M. L., and Dykman, R. A. (1998). Neuropsychological patterns in pediatric epilepsy. Seizure, 7(3), 223-228. Williams, J., Schulz, E., G., and Griebel, M. L. (2001). Seizure occurence in children diagnosed with ADHD. Clinical Pediatrics, (40), 221-224. Williams, J., Steel, C., Sharp, G. B., DelosReyes, E., Phillips, T., Bates, S., et al. (2003). Parental anxiety and quality of life in children with epilepsy. Epilepsy and Behavior, 4(5), 483-486. WHO. (2001). Classification of functioning, disability and health: ICF. Geneva: WHO. Wong, J., and Wirrell, E. (2006). Physical activity in children/teens with epilepsy compared with that in their siblings without epilepsy. Epilepsia (Series 4), 47(3), 631-639.
In: Society, Behaviour and Epilepsy Editors: Jaya Pinikahana and Christine Walker
ISBN 978-1-61761-001-1 © 2011 Nova Science Publishers, Inc.
Chapter XIII
Psychosocial Adjustment in Children with Epilepsy and Their Families Soraya Otero-Cuesta 1,2 and Amador Priede 1
1. Child and Adolecent Psychiatry and Psychology Unit, Department of Psychiatry, University Hospital Marques de Valdecilla, Santander, Cantabria, Spain 2. School of Medicine, University of Cantabria, Spain
Abstract Epilepsy is the most common chronic neurological illness in childhood and adolescence, and this condition increases the risk of psychopathology at these ages. Several studies find elevated rates of psychological and psychiatric disorders in these samples, both behavioural and emotional, compared to general population or children with other chronic conditions. The problems presented in children and adolescents with epilepsy are quite similar to those in general population with a slight increase of hyperkinetic and attention problems, as well as somatic complaints, likely related to both direct brain damage and anticonvulsant treatment. There is no evidence of psychotic disorders or specific personality traits associated with epilepsy at these ages. Psychopathology in children with epilepsy may be related with generic factors associated with children with chronic illnesses, such as withdrawn behaviour, somatic complaints, depression, delinquent behaviour, and aggressive behaviour. However, there are some symptoms relatively specific to children with epilepsy, for instance attention problems, social problems and thought problems. In spite of the biological basis of epilepsy, illness variables are weakly correlated with both psychological and social adjustment. Conversely, family factors such as parents' psychopathology, family coping with illness and stress and parent-child relationships seem to be the stronger predictors of child Correspondence: Soraya Otero MD PhD., Hospital U. M. Valdecilla, Unidad de Psiquiatría y Psicología InfantoJuvenil, c/ LV de Velasco nº1, 39011, Santander, Cantabria, Spain. Tel.: (+34) 942330311, Fax: (+34) 942344251. E-mail:
[email protected].
228
Soraya Otero-Cuesta and Amador Priede adjustment. Therefore parental expectations and attitudes towards epilepsy could affect a long term process of psychological adaptation to the disease. As well as this, family interactions may play a critical role in child adjustment. Main findings include patterns of overcontrol by parents and less child confidence and higher levels of family stress. Interestingly, epilepsy families form more efficient problem solving units than healthy control families. Nevertheless, children with epilepsy appeared to withdraw from family interaction. Other remarkable findings in terms of expressed emotion, links good treatment compliance with less maternal hostility and criticism and also good compliance with less psychiatric symptoms. Future directions, both in research and in intervention, should include the use of psychiatric interviews and direct observation to gather information on psychopathology instead of assessments exclusively relying on scales and questionnaires. Also, neuropsychological assessment and neurodevelopmental perspective are essential in order to reach a model explaining complexity of relationships between epilepsy, brain, and behaviour. Finally, more pragmatic research is needed, designing and evaluating preventive and therapeutic approaches, identifying groups at risk for social and psychological problems and those factors predicting lack of adherence to treatment. These groups at risk must be the target of efficient interventions. As a conclusion, in order to attend to the magnitude and extent of psychological problems in children and adolescents with epilepsy and their families, it is necessary to amplify the focus to a multi-disciplinary perspective, capable to deal with the different factors involved in the illness.
Introduction Childhood epilepsy is a biologically based risk factor for child and adolescent psychopathology and family adjustment problems. Epilepsy is the most common chronic neurological illness in childhood, in fact, the prevalence of epilepsy in school aged children is between 4 and 7 per 1000 (Kim, 1991; Rutter, 1970). The association between psychopathology and epilepsy is as old as the scientific characterization of illness. In recent decades, there has been increased research interest in this field mainly due to the recent development of specific measurement instruments in child psychiatry and the improving knowledge about neuro-development illness factors. At the same time, family and social aspects have been recognized as influential factors in adaptation to the illness. In recent years epilepsy and family have been considered relatively new focuses for research. Even when seizures are well controlled, family factors like psychological adjustment, attitudes and expectations may contribute to a long term process of adjustment to the disease. At the same time illness aspects influence family life. The unpredictability and the experience during the seizure of being out of control are traits that make epilepsy different from other chronic illnesses. There is a large number of studies on the psychological consequences of epilepsy for children and their families, with diverse methodologies and samples that make it difficult to find clear clinical and treatment implications. Some of these are dispersed and not easily available. There are misunderstandings associated with epilepsy, such as neurodevelopmental and intellectual deficits, and different types of seizures and classifications. Moreover studies on this field have focused in different aspects of psychiatric disturbance and family influences. It is important to consider some methodological issues of the studies in order to correctly understand the findings. Most of the studies about epilepsy and
Psychosocial Adjustment in Children with Epilepsy and Their Families
229
psychopathology are cross-sectional and retrospective studies, some of them with control group (healthy controls, siblings and/or children with other chronic illness, like asthma or diabetes). The cross-sectional design only allows for analysis of correlation and consequently, whether the child‘s behaviour problems are a response to the epilepsy within a strained family environment or whether the child‘s irritable and destructive behaviour leads to stress and strain for family members, or more possibly both, is still controversial. Also, it is important to note the heterogeneity of studies in this subject and the wide range of questionnaires and scales, using mother, father and teacher as informants about child behaviour. Most used methods to measure the psychopathology, including scales like the Rutter Scales (Rutter, 1970) and the Child Behaviour Check-list (CBCL) (Achenbach, 1991), and interviews like K-SADS. Also diverse scales for anxiety and depression have been used. Not only can epilepsy increase the risk of disturbance in the child but also seems to have an adverse effect on the health of the rest of family, particularly parents and siblings. Many factors may be involved with this increased vulnerability including the type and severity of epilepsy, therapeutic control, adverse effects of anticonvulsants, the individual characteristic of children and their families and the presence of psychopathology in the child or other family member.
Children with Epilepsy: Psychopathology and Adjustment Prevalence The large number of studies investigating the association of psychopathology and epilepsy demonstrate a more elevated rate of psychiatric disorders in these samples than in the general population of children or in children with other chronic illnesses. Children with chronic illnesses have a 2.5 times higher risk for psychopathology compared with healthy controls (Lavigne and Faier-Routman, 1993), but in the case of epilepsy the risk for psychopathology compared with healthy controls and children with non-CNS chronic illnesses is 3 to 9 times higher. The classic community study of neuropsychiatric disorders in the UK (Rutter, 1970) found that 28.6% of children with epilepsy have psychiatric disorders, in comparison of 6.6% rate of psychiatric disorders for children in general population and 11.6% rate for children with chronic physical disorders. More recent investigations set the prevalence of mental health problems range from 16% to 77% (Baker et al., 2005; Datta et al., 2005; Hoie et al., 2006; Rodenburg et al., 2006) as compared with 11% in children with other chronic illnesses like diabetes and 9% in the general paediatric population (Davies et al., 2003). Discrepancies in this wide range of psychopathology across studies may be explained as methodological differences between them. In general, structured psychiatric interviews (like K-SADS) identify higher rates of psychopathology as compared to self-report instruments (like CBCL), which may or may not include the child as an informant (Ott et al., 2001). Also higher rates of psychopathology are reported in patients with chronic epilepsy (Caplan et al., 2005; Caplan et al., 2004) compared with new onset (Austin et al., 2002; Austin et al., 2001),
230
Soraya Otero-Cuesta and Amador Priede
and in cross-sectional studies (Ettinger et al., 1998; Hanssen-Bauer et al., 2007; Ott et al., 2003) compared with longitudinal (Austin and Dunn, 2000).
Type of Disorders and Symptomatology Until recent years children with epilepsy were classified as having a typical syndrome characterised by over-activity, impulsivity, aggression and distractibility. But subsequent research has found that the most disturbed children with epilepsy have the same range and type of psychopathology as other disturbed children (Hoare, 1984b; Hoare and Kerley, 1991; Hoare and Kerley, 1992). Furthermore the concept of ―epileptic personality‖ must be abandoned. Moreover some of these ―hyperkinetic‖ features may be related to medication, mainly phenobarbitone and benzodiazepines. Community studies (Rutter, 1970) among children with uncomplicated epilepsy, find that 12.7% had emotional disorder, 7.5% had conduct disorder, 4.8% had mixed disorder, and 1.6% had hyperkinetic syndrome. In another study from Finland (Siianpää, 1973), including all types of epilepsy, the profile is different, with 29.7% of children with neurotic disturbance, 11% with autistic features or psychosis, and 33.5% with hyperkinetic disorder. The first studies in this area concluded that these children have more but not different psychopathology than children with other chronic illnesses like diabetes or asthma (Austin et al., 1994; Hoare, 1984b; Hoare and Mann, 1994). Several authors underline that neurotic or emotional disturbance is the most common diagnostic category (Hoare and Kerley, 1991; Long and Moore, 1979). More recent studies, including the first meta-analysis in this area, show that children with epilepsy are at increased risk for the whole range of psychopathology (Rodenburg et al., 2005b). However, somatic complaints and attention problems are the most salient symptoms. Also, children with epilepsy appear to experience more internalizing (typified by social withdrawal, somatic complaints, anxiety, and depression) than externalizing (typified by aggression, defiance, hyperactivity and conduct problems) behaviour problems, though the rate of externalizing problems remains consistently high. According to these findings psychopathology in children with epilepsy is partly associated with generic factors associated with chronic illnesses in childhood, such are withdrawn behaviour, somatic complaints, depression, delinquent behaviour, and aggressive behaviour. Nevertheless, attention problems, social problems and thought problems are relatively specific to children with epilepsy as opposed to children with other chronic illnesses. Family factors (see below) are related more strongly to those behaviour problems that are relatively common to chronic diseases (namely, externalizing behaviour, withdrawal, and depression). In contrast, its not clear if the role of family factors contributes to behaviour problems that are more specific to epilepsy (namely, attention problems, thought problems, and social problems) (Rodenburg et al., 2005b).
Gender Gender variations are not consistent. While some studies found that boys with epilepsy show more problematic psychological adjustment than girls with epilepsy, (Hoare and Mann,
Psychosocial Adjustment in Children with Epilepsy and Their Families
231
1994; Stores and Piran, 1978) others found that girls have more depressive symptoms, somatic complaints, hyperactivity and withdrawal symptoms than boys (Austin, 1989; Austin et al., 1992). Some studies have not shown any gender differences (Baki et al., 2004; Hoare and Kerley, 1991; Rutter, 1970).
Child Adjustment and Self-Esteem Other aspects concerning child psychology have been investigated, for instance, children with epilepsy are more dependent than children with other chronic conditions like cystic fibrosis (Hartlage et al., 1972) or diabetes (Hoare, 1984b). The findings are related to neither illness severity nor parental attitudes. Self-esteem, self-concept and adjustment are related to psychopathology: children with behavioural problems have worse self-esteem (Hoare and Mann, 1994). Children with epilepsy have poorer psychosocial adjustment at school, more depressive symptoms, and worse self-concept than children with asthma (Austin, 1988). Furthermore, patients with epilepsy with the difficulties mentioned above ("worse adjustment at school, more depressive, and so on") are found to have worse seizure control rates than those with good adjustment or without depression (Austin, 1989). This study underlines the continuity of depressive symptoms in adult life of some people suffering from epilepsy and suggests that poor self-esteem, a symptom of depression, could begin from childhood.
Social Problems and Quality of Life Children with epilepsy are at increased risk for social difficulties compared with other children (Jacoby and Austin, 2007) and with siblings. Drewel and Caplan (Drewel and Caplan, 2007) found that children with epilepsy demonstrate lower social competence and more peer difficulties than typically-developing children or children with non-central nervous system health problems. These researchers‘ findings also indicated that social difficulties in children with epilepsy have been related, in a number of studies, to the cognitive, psychological and linguistic deficits seen in these children (e.g., lower IQ, externalizing and anxious behaviour and social communication deficits). Also, children with epilepsy, especially those with complicated early-onset epilepsy, had fewer age-appropriate social skills and more attention and behaviour problems than the healthy children (Rantanen et al., 2009). It is possible that the lack of age-appropriate social skills and the presence of attention problems make children prone to behavioural problems. Children with epilepsy also have social problems with peers (Drewel and Caplan, 2007). Behaviours related to anxiety and inattention are associated with difficulties with peers in children with epilepsy. Similarly, some epilepsy-related factors, such as neuropsychological deficits, earlier age at epilepsy onset, and active seizure status, are indirectly related to peer difficulties and directly related to anxious and inattentive behaviours in children with epilepsy. General theoretical models of peer difficulty would be useful also for children with epilepsy because of the similarities between these children and typically developing children with regard to variables related to their peer problems.
232
Soraya Otero-Cuesta and Amador Priede
Multiple studies have investigated the concept of Health Related Quality Of Life which does not directly evaluate psychopathology, but instead a patient's self-perceptions of wellbeing in the physical, mental, and social domains of life. Children with epilepsy are more impaired in Health Related Quality Of Life than healthy controls (Austin and Dunn, 2000; Connolly et al., 2006; Cramer et al., 1999; Miller et al., 2003; Raty et al., 2003) and children with non-neurological chronic illnesses (Hoare et al., 2000). Illness Variables The association between psychological adjustment and illness variables has been frequently investigated as a central point. The severity of illness predicts only in part psychosocial functioning and adjustment, and it could be analysed in different aspects:
Frequency and type of seizures: higher frequency of seizures is associated with less social development but not with differences in academic achievement, and type of seizure is not significantly correlated with either of them (Hartlage and Green, 1972; Hartlage et al., 1972). In addition, other illness factors significantly associated with more psychological disturbance, are complex partial seizures, focal abnormalities in EEG, and severe fit frequency. Length of illness: there is a consistent relationship between the length of epilepsy and psychopathology in most of the studies (Rodenburg et al., 2005a; Rodenburg et al., 2005b). The length of illness has been associated with more prevalence of psychological problems not only in children but also in their relatives (Hoare, 1984a; Hoare, 1984b). An early onset of seizures can affect academic and social development. Degree of seizure control: children with a poorer control of seizures are more prone to social withdrawal, and have more somatic complaints than those with a better control. In samples of adolescents with epilepsy, the degree of seizure control, polimedication and stigma aspects are significantly associated with internalizing disorders and adaptation problems in these subjects (Adewuya and Ola, 2005). Children with intractable epilepsy are highly at risk for attention and thought problems, but also for social problems, withdrawn behaviour, and somatic complaints.
The influence of some of these variables could be modulated by the level of others: the studies (Rodenburg et al., 2005a; Rodenburg et al., 2005b) suggest that in those children with good seizure control, illness variables, except length of illness, are not related to psychological and adaptation problems. However in those children with more severe illness and/or poorer seizure control, illness variables have a significant impact on psychopathology. Family variables, illness influence on family life and family ability in coping with stress have been suggested as mediated factors on children psychopathology. Cognitive aspects of children with epilepsy such as IQ and linguistic competence have been related to illness variables (illness length, seizure frequency) and to antiepileptic drugs (Caplan et al., 2004; Rodenburg et al., 2006).
Psychosocial Adjustment in Children with Epilepsy and Their Families
233
Other studies offer a quite different profile underlining the absence of association between illness variables such as the severity or specific type of epilepsy and psychopathology in children with epilepsy (Caplan et al., 2004; Kim, 1991). Quality of life is affected in more severe cases and when these cases are considered, including those with brain damage, the results seem to be modified, showing that the quality of life is adversely affected mainly in the group of early onset intractable epilepsy with additional disabilities, and that poorer control of epilepsy is associated with more negative impact on family life (Hoare, 1993; Hoare and Russell, 1995). It is supposed that neurological dysfunction causes both behaviour problems and seizures. This does not exclude the fact, however, that other risk factors contribute to behaviour problems in children with enduring epilepsy. Children with uncontrollable seizures are especially at risk for the development of behaviour problems. Problems inherent to chronic diseases — such as unpredictability, distress, medication regimen, social stigma, and family stress — may arise in children with longer lasting epilepsy apart from neurological dysfunction.
Family Factors Family Psychopathology and Adjustment Parents Epilepsy is a chronic stressful condition for family life, and this could have consequences on the mental health of family members. Parents of children with epilepsy are more affected than those of the general population (Hoare, 1984a). Most studies show a concordance between psychological problems in mothers and behavioural problems in children with epilepsy (Rutter, 1970; Hoare and Kerley, 1991; Hodes et al., 1999; Otero and Hodes, 2000). Some researchers (Hoare, 1984a) suggested that this association could be modulated by the length of the illness, in fact it appeared only in those children with more years of evolution. There is a consistent relation between maternal depression and child psychopathology (Brennan et al., 2000; Dawson et al., 2003). Some investigators propose that this relation may happen through the disruption of quality of parenting (Burke, 2003; Dekovic et al., 2003). About one-third of the mothers of children with epilepsy are at increased risk for depression and showed associations between maternal depression and higher levels of child psychopathology (Hoare, 1984c; Hodes et al., 1999; Shore et al., 2004). Mothers of children with epilepsy are at risk for problems in adapting to their child's condition (Shore et al., 2004), and may be at risk also for anxiety (Li et al., 2008). However, some studies did not detect a difference in anxiety level between mothers of children with epilepsy and mothers of children without epilepsy (Baki et al., 2004; Williams et al., 2003). Mothers with higher levels of generalized anxiety are more anxious about their child‘s epilepsy (Chapieski et al., 2005). Nonetheless, coping resources of the mother may mediate the effects of generalized anxiety. Mothers who had social supports, or were comfortable talking about emotions, were less anxious about their child‘s epilepsy. However, family stress may aggravate maternal anxiety about seizures. In any case, maternal anxiety about epilepsy appears to decrease over time.
234
Soraya Otero-Cuesta and Amador Priede
Another important aspect of the relationship between the family and epilepsy concern the fictitious seizures induced by a relative. False epilepsy is not rare, because it is easy to fabricate and there are no absolute pathological or electrophysiological test that can diagnose the disorder. Most of these patients have occasional real seizures and additional multiple fictitious seizures induced by a relative, usually the mother. Apart from an increased risk for other fictitious disorders and/or child abuse, they were more likely to have had more physical investigations, and more hospital admissions, were absent from school and the prescribed drugs were commonly given irregularly. The follow-up of these children suggests an increasing risk for abnormal illness behaviour, fictitious disorder or chronic invalidism in adulthood. In these families, mother is described as dominant and the father absent or weak. Most of these mothers are ―hospital addicts‖ and over-involved with their children‘s care. Siblings Psychological problems of siblings have been often analyzed, and frequently healthy siblings are control groups of studies measuring psychopathology and behavioural problems in children with epilepsy. Siblings have fewer psychological problems than their brothers or sisters with epilepsy but were more disturbed than children in the general population (Hoare, 1984a). Siblings were found at elevated risk, with 25% being rated as disturbed (Hoare and Kerley, 1991). Interestingly, siblings of children with chronic epilepsy are more affected than those of newly diagnosed children.
Family Structure and Socio-Demographic Factors In most of the studies family structure, socio-economic, and culture are considered as descriptive variables but their interactions with epilepsy, psychopahology or other family factors are not analysed. The few studies considering a wide spectrum of family structure and socio-economic status generally failed to show an association between psychopathology and these variables (Austin et al., 1992; Rutter, 1970). However in one study, mothers from lower socioeconomic status were found more likely to report elevated anxiety about their children‘s medical condition (Chapieski et al., 2005). Probably their lower level of education made it more difficult for them to take advantage of information they received about epilepsy which increased their anxiety levels. The influence of culture is analysed, as far as we know, in only one study (Chavez and Buriel, 1988). They found that immigrant Mexican mothers exhibited a more positive feed-back to their epileptic children that their native-born Mexican-American counterparts.
Family Knowledge, Expectations and Attitudes Since most of the studies on psychopathology and epilepsy gather information from parents and teachers, it is of interest to review those studies regarding knowledge, expectations and attitudes of adults towards boys and girls suffering from epilepsy. Parents may show diminished expectations for their children with epilepsy in school outcomes, sports, concentration and choice of occupation, and they are expected to be more prone to emotional problems than their healthy siblings (Hartlage and Green, 1972). The parents
Psychosocial Adjustment in Children with Epilepsy and Their Families
235
perceive themselves as stricter and are more dominant in relation to their children with epilepsy. Families perceive their children with epilepsy as having a higher frequency of aggressive behaviour toward parents, with more immature behaviour, more dependency, expressing complaints of personal rejection and having frequent periods of emotional distress (Austin and McDermott, 1988; Ferrari et al., 1983; Hoare, 1986). Parental attitudes towards epilepsy are more equilibrated with both positive and negative expectations. Parents of children with epilepsy (Hoare, 1986) are realistic about the problems for their children, and have appropriate knowledge about seizures, illness and educational problems. There were no differences between mother's and father's attitudes, but they were more negative towards girls than boys (Austin et al., 1984). An interesting finding (Hoare, 1986) is that parental perception of seizure control is a better predictor of parental adjustment than the level of seizure control itself. In addition, parental attitudes towards their children with epilepsy seem to improve with the length of the illness (Austin and McDermott, 1988).
Family Interaction and Children Psychological Adjustment Studies Using Reports Most studies of family interaction rely on parental report. Only a minority of studies use direct observation of family interactions, all in laboratory settings. The main findings of studies about family interaction are the association between over-control by parents with less child confidence and more behavioural and emotional problems reported by parents, teachers and children (Carlton-Ford et al., 1997). Other studies show an association between parental acceptance and lower levels of externalizing behaviour problems (Sbarra et al., 2002). It is of interest that mothers who express more anxiety about their children‘s epilepsy are more likely to adopt a protective parenting style and to be more involved in solving problems for their children (Chapieski et al., 2005). This protective parenting style, however, was found to have a negative effect on the child‘s level of adaptive functioning in social situations and managing the requirements of daily living. Marital relationship has been considered a descriptive variable in some studies. For example, the Isle of Wight study (Rutter, 1970) does not find differences in psychological adjustment between children from broken and children from ―normal‖ homes. However, Ferrari et al. (1983) finds less cohesion and poorer communication between these families and lower prevalence of reported family closeness between the members of the families. They suggest that it could be an outcome of high marital discord. In the study of Hoare and Kerley (1991) the mean of marital satisfaction rating was within the over-all wide range for the general population. Expressed emotion studies (Hodes et al., 1999) conclude that mothers showed significantly more emotional over-involvement and a trend to have more hostility towards their children with epilepsy than towards sibling controls. High levels of criticism and, to a lesser extent hostility, are associated with child behavioural deviance. Strong links were found between maternal criticism and overactive behaviour in the child. Fewer positive
236
Soraya Otero-Cuesta and Amador Priede
comments by mothers towards the children are associated with child emotional symptoms and lower self-esteem. Family stress is significantly higher in families having a child with epilepsy, according to self-reports, in aspects related to dependency, cognitive impairment, restrictions for family, long-term care, anxiety about life expectancy and burden for parents (Rutter, 1970; Hoare and Kerley, 1991; Pianta and Lothman, 1994). Moreover parent–child relationship quality (Pianta and Lothman, 1994; Hodes et al., 1999) and parenting (Austin et al., 2004) are important contributors to child psychopathology, and parents of children with chronic conditions experience higher levels of parenting stress (Britner, 2003; Powers et al., 2002; Streisand et al., 2005). This stress probably has its origin in the burden of the care and the demands of a chronic illness (Wallander and Varni, 1998). In the case of children with epilepsy, parenting stress is even higher than in other chronic illnesses like asthma (Chiou and Hsieh, 2008). Rodemburg et al. (2007) found that stressors, resources, and parental coping behaviours are all significant contributors to parenting stress. The factors that would increase parenting stress are child‘s functional status, difficult child temperament, parental depression, and emotionfocused coping behaviours. Above all, parental emotion-focused coping behaviours are a major contributor to parenting stress. Factors that also contribute to lower levels of parenting stress are social support, family cohesion, and problem-focused coping behaviours. Parental perceptions of the child‘s functional status are associated with increased parenting stress, which may affect the degree of supportive parenting and parent–child relationship quality. Thus, the degree to which parents perceive child behavioural problems increases parenting stress, which subsequently impacts their affective and responsive parenting behaviours and compromises relationship quality. This may, in turn, have considerable consequences for child adjustment (Bleil et al., 2000). Difficult child temperament may lead to both, poorer parent–child relationship quality, and parents‘ ability to adequately control the child. Besides, parental depression impacts on parental behavioural and psychological control via parenting stress. This is in line with the existing literature about depressed mothers in the general population, who exhibit more hostile and intrusive behaviours toward their child and are less involved with their child (Goodman and Gotlib, 1999). Family cohesion contributes to lower levels of parenting stress, and leads to higher levels of parental behavioural control. Furthermore, the presence of social support also reduced parenting stress, which, in turn, contributed to higher levels of parental behavioural control and psychological control. Finally, problem-focused coping behaviours have direct effects on supportive parenting. In contrast, the effects of emotion-focused coping behaviours is an ineffective coping style, and lead to higher levels of parenting stress, which, in turn, leads to less behavioural control and higher levels of psychological control.
Studies Using Direct Observational Methods The studies using direct observational instruments display interesting information on behavioural patterns and interactions between family members. These findings include the fact that epilepsy families form more efficient problem solving units than healthy control families (Ritchie, 1981). The children with epilepsy appeared to withdraw from family interaction. A similar organisation was found in families with a child with mental retardation, and that was hypothesised to be adaptive in coping with the illness.
Psychosocial Adjustment in Children with Epilepsy and Their Families
237
Chavez and Buriel (1988) when comparing mother-child interaction between groups of children with epilepsy, asthma and healthy controls find differences in speech and non verbal interactions with fewer positive responses from mothers with children with epilepsy. Additionally, the children with epilepsy fail more often on structured tasks than children with either asthma or good health. Using interesting observational methodology the studies of the University of Virginia (Lothman and Pianta, 1993; Pianta and Lothman, 1994) underline the importance of parenting in the adjustment of children affected by epilepsy and the impact of epilepsy on parenting and family. Their hypothesis was that the fact that quality of child-mother relationship would increase child outcome beyond disease factors or child characteristics. This team developed several rates of mother behaviour with her child in two videotaped tasks, on the following dimensions: emotional support, respect for child autonomy, and quality of instruction. Moreover they rate observational measures of a child‘s independent problem solving on the following dimensions: confidence, self-control, task involvement, flexibility, dependency, task focus, positive affect and negative affects. These observational measures are correlated with ratings for parents and teachers about children competence. Their findings suggest that psycho-social adjustment in children is related to both parenting variables and child factors and that mother-child interaction correlated with teacher ratings about children‘s competence, behavioural problems and also with child confidence/involvement in a problem-solving situation requiring them to work independently. They correlate measures of mother-child interaction with behavioural problems measured with Child Behaviour Checklist (CBCL). The ratings of a child‘s self-reliance and co-ordination of affection in the mother-child relationship during the problem solving situation account for the largest variance of behaviour problems, especially with problems reported by parents (Pianta and Lothman, 1994). In addition when the sample is divided into two groups according to degree of seizure control, the analysis shows few differences between both groups in CBCL scales: only in somatic complaints on teachers ratings and in anxiety/depression, social, thought and attention problems on parents ratings, suggesting once again that mother-child interaction was a stronger predictor of children adjustment problems than seizure control (Nicholas, 1994).
Integrating Findings about Family Interactions and Psychopathology In a study of Rodemburg et al. (2006), analyzing predictors of psychopathology in children and adolescents with epilepsy, they found that family factors significantly influenced almost each type of child psychopathology. However, when the other significant family factors were controlled for, only the quality of parent–child relationship exerted influence on child psychopathology, whereas other significant effects of distal and contextual factors disappeared. Thus, the parent–child relationship quality was found to be the most important contributor to child psychopathology, and it would mediate the effects of distal (parental characteristics) and contextual (quality of other family relationships) family factors. As is quoted above, consistently through the studies, family factors are related more strongly to those behaviour problems that are relatively common to chronic diseases and they are more strongly related to psychopathology in children with epilepsy than are epilepsy-related factors. Thus authors come to the conclusion that these findings indicate that it is especially
238
Soraya Otero-Cuesta and Amador Priede
the presence of a chronic condition that places demands on the family, rather than the effects of specific disease parameters. Some authors have proposed models regarding families with a member affected by a chronic illness that could be useful in helping us understand and integrate the findings in these families. The Structural Family Model proposed a model of families with a chronic illness (Minuchin et al., 1975). They consider that there are some other elements defining these families besides the physiological disorder present in a chronic somatic illness. First, enmeshment with great interdependence and weak subsystem boundaries. Second, overprotectiveness from parents delaying the development of child‘s competence and autonomy. Also overprotectiveness by the child who protects the family by using his or her symptoms. Third, rigidity and denial of the need for a change, and fourth, as a consequence of these three previous conditions, these families avoid conflict resolution since the ill child plays an important role in this avoidance. This type of family interaction pattern is prone to use illness as a means of communication (Minuchin et al., 1975). There is no serious research on this model but some consistent findings such as more dependency in the child, overprotectiveness and problems in coping with the illness in some of these families seem to give some support to this model. Another model related to the previous is the Bio-behavioural Family Model of chronic illness (Wood, 1994). It proposed a model with integration of individual, family and social factors and offered therapeutic approach to families with children with a chronic illness. This model added a psychobiological factor, the bio-behavioural reactivity, which is conceptualised as a degree of physiological, emotional or behavioural response to stimuli. Table 1. Main findings regarding psychopathology and psychological adjustment in children with epilepsy Prevalence More elevated rate of psychiatric disorders in children with epilepsy than in the general population of children or in children with other chronic illnesses Specific findings Children with epilepsy are at increased risk for the whole range of psychopathology. Some of the psychological problems would be related with generic factors associated with chronic illnesses (such as withdrawn behavior, somatic complaints, depression, delinquent behavior, and aggressive behaviour). Other psychological problems would be associated with specific factors to children with epilepsy (attention problems, social problems and thought problems). Children with epilepsy are more dependent, have worse self-concept and poorer psychosocial adjustment. Increased risk for social difficulties, lower social competence and more peer difficulties Illness variables More frequency of seizures is associated with less social development. Consistent relationship between the length of epilepsy and psychopathology. Children with a poorer control of seizures are more prone to social withdrawal, and have more somatic complaints. Family factors Family factors are consistently related with behavior problems in children with epilepsy and stress is suggested as a mediating factor.
Psychosocial Adjustment in Children with Epilepsy and Their Families
Schema 1. model for integration of findings and future research
239
.
According to this model a high level of individual reactivity in the child with epilepsy is a risk factor for chronic disease activity. A second factor, interpersonal responsivity, is determined in part by individual bio-behavioural reactivity, and defined as the degree of physiological, emotional or behavioural response with which family members respond to each other. Studies on Expressed Emotion in families with a child affected by epilepsy or other chronic illnesses can give indirect support to this model. In addition, other family factors such are proximity, generational hierarchy, triangulation and dysfunctional parental relationship also play a role in ―drawing‖ the maladaptive family configuration. The author proposed several models of dysfunctional family configurations and specific techniques to modify these maladaptive structures (see Table 1 and schema 1)
Intervention Programs for Families There are few studies of psychological interventions for families with children with epilepsy. Lewis et al. (1990) conducted a randomised controlled study to test the efficacy of a child and a program focused on family intervention in the experimental group. This was a study with a control group and all participants were pre-tested and re-tested five months after the completion of the educational intervention. The study showed that, an educational intervention to teach decision-making and communication skills, was more effective than the traditional lecture/question and passive format questions in children groups. In families, the experimental group improved their knowledge and skills to manage seizures at home and reported reduction in visits to emergency room, as well as the associated stress. Moreover
240
Soraya Otero-Cuesta and Amador Priede
they reported they were less restrictive with the child and permitted their child to participate more often in decisions regarding self-care and seizure control. Parental anxiety was reduced after the intervention in the experimental group. Hoare and Kerley (1991, 1992) proposed a group programme for parents with a child suffering from epilepsy and analysed the participation, responses and expressed need in these families. This intervention project was unsuccessful because only 12% attended the meetings with high attrition rate. The parents who attended the programme had children with severe epilepsy and educational or family problems. The authors suggested that individual or group programmes carried out in order to reduce anxiety or improve social skills in these children are more likely to be successful. Some new interventions have been created in the last decade, showing that they may be beneficial for family adaptation to epilepsy. Austin et al. (2002) developed a psychoeducational family intervention, called "Be Seizure Smart," focused on improving attitudes and increasing family functioning. The intervention was individually adapted to each family member by (a) providing information about epilepsy, treatment, and seizure management according to the individual's knowledge base, (b) addressing unique concerns and fears, and (c) providing emotional support. It increased the information and knowledge level for both parents and children. Children had fewer concerns and were more satisfied with family relationships. Also, child and parent attitudes were more positive after the intervention. Shore et al. (2008) investigated the usefulness of the Seizures and Epilepsy Education (SEE) program about the improvement of life quality, management of the seizure condition, and healthcare implementation in families having a child with epilepsy. Both parents and children after attending the SEE program improved their quality of life relating to child mental health. Parents had less emotional impact on the child‘s condition, fewer worries, and greater knowledge related to epilepsy. Another aspect of the link between family, epilepsy and treatment is therapeutic compliance. Lack of adherence to medical regimens is a frequent problem, especially in the child with epilepsy since successful treatment is based on the regular intake of anticonvulsant drugs. Using protocols developed from the Theory of Reasoned Action (Ajzen, 1980), Austin et al. (1989b), measured behavioural intention, attitude towards behaviour and subjective norms, and also medication giving behaviour, reported by the parents through mail. According to this model, behavioural intention influences behavioural compliance, and is a function of both, attitude towards the specific behaviour and subjective norms. The results suggest that subjective norms are the stronger predictor of parental compliance behaviour, but also parent‘s attitudes toward giving anticonvulsant medication and behavioural intention are important in the prediction. Regarding parent-child relationships it has been concluded that good treatment compliance is associated with less maternal hostility and criticism, and suggests that assertive paediatric and psychosocial intervention may be useful for some children with epilepsy (Otero and Hodes, 2000).
Conclusions Nearly forty years of investigations concerning psychopathology in children with epilepsy have led us to a better understanding of the underlying processes involved in
Psychosocial Adjustment in Children with Epilepsy and Their Families
241
children and family adaptation to the illness (Otero, 2009; Plioplys et al., 2007; Rodenburg et al., 2005b). Children with epilepsy are at higher risk for the whole range of psychopathology. Psychopathology should be divided into two groups, on the one hand, attention problems, social problems and thought problems that may be related to epilepsy as a brain dysfunction, and on the other hand withdrawn behaviour, somatic complaints, depression, delinquent behaviour, and aggressive behaviour which are more related to epilepsy as a chronic condition. Also, parents and siblings of these children are more prone to the development of psychopathology compared with the general population, due to the fact that epilepsy is a chronic stressful condition for family life. Epilepsy and family is an important focus because psychopathology in children with epilepsy is more related to family factors than to epilepsyrelated factors. Only length of illness can play a minor role, affecting adaptation of children. There is a wide range of findings and heterogeneity in the field of the psychopathology in children with epilepsy and their families. An integrated model on epilepsy and family may be useful to organise information and design both intervention programs and future research. Our global schema (see schema 1) includes family interactions, behavioural and emotional aspects in children with epilepsy and illness factors. Nothing about cause-effects direction is clearly known but these aspects are the real challenge for future research. The magnitude and extent of problems in children and adolescents with epilepsy and their families make it necessary to focus on the problem from a transdisciplinary and multiaetiology perspective considering the bi-directional interactions between all involved variables. It should be important to take the following advice into consideration in order to perform better interventions. First of all, we should improve instruments and protocols to identify those children and adolescents with epilepsy at risk for developing psychopathology. Secondly we should consider the whole family in the treatment, in order to increase family adaptation, and to reduce parental responses of anxiety and depression. These interventions should include suitable information about the illness, strategies to reduce parent stress and provide problem-focused coping strategies. This point is also important for investigation goals, because the studies of interaction may bring more complete understanding about the variables influencing outcomes in child and adolescents suffering from epilepsy. Finally, a developmental point of view would be useful in order to clear the age influence and effects of epilepsy on different development tasks, effects of timing of onset and possible residual effects if it remits.
References Achenbach, T. M. (1991). Manual for Child Behavior Checklist/ 4-18 and 1991 Profile. Burlington, VT: University of Vermont, Dept. of Psychiatry. Adewuya, A. O., and Ola, B. A. (2005). Prevalence of and risk factors for anxiety and depressive disorders in Nigerian adolescents with epilepsy. Epilepsy Behav, 6(3), 342347. Ajzen, I., and Fishbein, M. (1980). Understanding attitudes and predicting social behavior. Englewood Cliffs, NJ: Prentice-Hall. Austin, J. K. (1988). Childhood epilepsy: child adaptation and family resources. J. Child Adolesc. Psychiatr Ment. Health Nurs, 1(1), 18-24.
242
Soraya Otero-Cuesta and Amador Priede
Austin, J. K. (1989a). Comparison of child adaptation to epilepsy and asthma. J. Child Adolesc. Psychiatr Ment. Health Nurs, 2(4), 139-144. Austin, J. K. (1989b). Predicting parental anticonvulsant medication compliance using the theory of reasoned action. J. Pediatr Nurs, 4(2), 88-95. Austin, J. K., and Dunn, D. W. (2000). Children with epilepsy: quality of life and psychosocial needs. Annu. Rev. Nurs Res, 18, 26-47. Austin, J. K., Dunn, D. W., Caffrey, H. M., Perkins, S. M., Harezlak, J., and Rose, D. F. (2002). Recurrent seizures and behavior problems in children with first recognized seizures: a prospective study. Epilepsia, 43(12), 1564-1573. Austin, J. K., Dunn, D. W., Johnson, C. S., and Perkins, S. M. (2004). Behavioral issues involving children and adolescents with epilepsy and the impact of their families: recent research data. Epilepsy Behav, 5 Suppl 3, S33-41. Austin, J. K., Harezlak, J., Dunn, D. W., Huster, G. A., Rose, D. F., and Ambrosius, W. T. (2001). Behavior problems in children before first recognized seizures. Pediatrics, 107(1), 115-122. Austin, J. K., McBride, A. B., and Davis, H. W. (1984). Parental attitude and adjustment to childhood epilepsy. Nurs Res, 33(2), 92-96. Austin, J. K., and McDermott, N. (1988). Parental attitude and coping behaviors in families of children with epilepsy. J. Neurosci. Nurs, 20(3), 174-179. Austin, J. K., McNelis, A.M., Shore, C.P., Dunn, D.W. and Musick, B. (2002). A feasibility study of a family seizure management program: 'Be Seizure Smart'. The Journal of neuroscience nursing, 34(1), 30-37. Austin, J. K., Risinger, M. W., and Beckett, L. A. (1992). Correlates of behavior problems in children with epilepsy. Epilepsia, 33(6), 1115-1122. Austin, J. K., Smith, M. S., Risinger, M. W., and McNelis, A. M. (1994). Childhood epilepsy and asthma: comparison of quality of life. Epilepsia, 35(3), 608-615. Baker, G. A., Spector, S., McGrath, Y., and Soteriou, H. (2005). Impact of epilepsy in adolescence: a UK controlled study. Epilepsy Behav, 6(4), 556-562. Baki, O., Erdogan, A., Kantarci, O., Akisik, G., Kayaalp, L., and Yalcinkaya, C. (2004). Anxiety and depression in children with epilepsy and their mothers. Epilepsy Behav, 5(6), 958-964. Bleil, M. E., Ramesh, S., Miller, B. D., and Wood, B. L. (2000). The influence of parent-child relatedness on depressive symptoms in children with asthma: tests of moderator and mediator models. J. Pediatr Psychol, 25(7), 481-491. Brennan, P. A., Hammen, C., Andersen, M. J., Bor, W., Najman, J. M., and Williams, G. M. (2000). Chronicity, severity, and timing of maternal depressive symptoms: relationships with child outcomes at age 5. Dev. Psychol, 36(6), 759-766. Britner, P. A., Morog, M.C., Pianta, R.C. and Marvin, R.S. (2003). Stress and coping: a comparison of self-report measures of functioning in families of young children with cerebral palsy or no medical diagnosis. J. Child Fam. Stud, 12, 335-348. Burke, L. (2003). The impact of maternal depression on familial relationships. Int. Rev. Psychiatry, 15(3), 243-255. Caplan, R., Siddarth, P., Gurbani, S., Hanson, R., Sankar, R., and Shields, W. D. (2005). Depression and anxiety disorders in pediatric epilepsy. Epilepsia, 46(5), 720-730.
Psychosocial Adjustment in Children with Epilepsy and Their Families
243
Caplan, R., Siddarth, P., Gurbani, S., Ott, D., Sankar, R., and Shields, W. D. (2004). Psychopathology and pediatric complex partial seizures: seizure-related, cognitive, and linguistic variables. Epilepsia, 45(10), 1273-1281. Carlton-Ford, S., Miller, R., Nealeigh, N., and Sanchez, N. (1997). The effects of perceived stigma and psychological over-control on the behavioural problems of children with epilepsy. Seizure, 6(5), 383-391. Connolly, A. M., Northcott, E., Cairns, D. R., McIntyre, J., Christie, J., Berroya, A., Lawson, J. A., Bleasel, A. F. and Bye, A. M. (2006). Quality of life of children with benign rolandic epilepsy. Pediatr Neurol, 35(4), 240-245. Cramer, J. A., Westbrook, L. E., Devinsky, O., Perrine, K., Glassman, M. B., and Camfield, C. (1999). Development of the Quality of Life in Epilepsy Inventory for Adolescents: the QOLIE-AD-48. Epilepsia, 40(8), 1114-1121. Chapieski, L., Brewer, V., Evankovich, K., Culhane-Shelburne, K., Zelman, K., and Alexander, A. (2005). Adaptive functioning in children with seizures: impact of maternal anxiety about epilepsy. Epilepsy Behav, 7(2), 246-252. Chavez, J. M., and Buriel, R. (1988). Mother-child interactions involving a child with epilepsy: a comparison of immigrant and native-born Mexican Americans. J. Pediatr Psychol, 13(3), 349-361. Chiou, H. H., and Hsieh, L. P. (2008). Parenting stress in parents of children with epilepsy and asthma. J. Child Neurol, 23(3), 301-306. Datta, S. S., Premkumar, T. S., Chandy, S., Kumar, S., Kirubakaran, C., Gnanamuthu, C. and Cherian, A. (2005). Behaviour problems in children and adolescents with seizure disorder: associations and risk factors. Seizure, 14(3), 190-197. Davies, S., Heyman, I., and Goodman, R. (2003). A population survey of mental health problems in children with epilepsy. Dev. Med. Child Neurol, 45(5), 292-295. Dawson, G., Ashman, S. B., Panagiotides, H., Hessl, D., Self, J., Yamada, E. and Embry, L. (2003). Preschool outcomes of children of depressed mothers: role of maternal behavior, contextual risk, and children's brain activity. Child Dev, 74(4), 1158-1175. Dekovic, M., Janssens, J. M., and Van As, N. M. (2003). Family predictors of antisocial behavior in adolescence. Fam. Process, 42(2), 223-235. Drewel, E. H., and Caplan, R. (2007). Social difficulties in children with epilepsy: review and treatment recommendations. Expert Rev. Neurother, 7(7), 865-873. Ettinger, A. B., Weisbrot, D. M., Nolan, E. E., Gadow, K. D., Vitale, S. A., Andriola, M. R., Lenn, N. J., Novak, G. P. and Hermann, B. P. (1998). Symptoms of depression and anxiety in pediatric epilepsy patients. Epilepsia, 39(6), 595-599. Ferrari, M., Matthews, W. S., and Barabas, G. (1983). The family and the child with epilepsy. Fam. Process, 22(1), 53-59. Goodman, S. H., and Gotlib, I. H. (1999). Risk for psychopathology in the children of depressed mothers: a developmental model for understanding mechanisms of transmission. Psychol. Rev, 106(3), 458-490. Hanssen-Bauer, K., Heyerdahl, S., and Eriksson, A. S. (2007). Mental health problems in children and adolescents referred to a national epilepsy center. Epilepsy Behav, 10(2), 255-262. Hartlage, L. C., and Green, J. B. (1972). The relation of parental attitudes to academic and social achievement in epileptic children. Epilepsia, 13(1), 21-26.
244
Soraya Otero-Cuesta and Amador Priede
Hartlage, L. C., Green, J. B., and Offutt, L. (1972). Dependency in epileptic children. Epilepsia, 13(1), 27-30. Hoare, P. (1984a). The development of psychiatric disorder among schoolchildren with epilepsy. Dev. Med. Child Neurol, 26(1), 3-13. Hoare, P. (1984b). Does illness foster dependency? A study of epileptic and diabetic children. Dev. Med. Child Neurol, 26(1), 20-24. Hoare, P. (1984c). Psychiatric disturbance in the families of epileptic children. Dev. Med. Child Neurol, 26(1), 14-19. Hoare, P. (1986). Adults' attitudes to children with epilepsy: the use of a visual analogue scale questionnaire. J. Psychosom. Res, 30(4), 471-479. Hoare, P. (1993). The quality of life of children with chronic epilepsy and their families. Seizure, 2(4), 269-275. Hoare, P., and Kerley, S. (1991). Psychosocial adjustment of children with chronic epilepsy and their families. Dev. Med. Child Neurol, 33(3), 201-215. Hoare, P., and Kerley, S. (1992). Helping parents and children with epilepsy cope successfully: the outcome of a group programme for parents. J. Psychosom. Res, 36(8), 759-767. Hoare, P., and Mann, H. (1994). Self-esteem and behavioural adjustment in children with epilepsy and children with diabetes. J. Psychosom. Res, 38(8), 859-869. Hoare, P., Mann, H., and Dunn, S. (2000). Parental perception of the quality of life among children with epilepsy or diabetes with a new assessment questionnaire. Qual. Life Res, 9(6), 637-644. Hoare, P., and Russell, M. (1995). The quality of life of children with chronic epilepsy and their families: preliminary findings with a new assessment measure. Dev. Med. Child Neurol, 37(8), 689-696. Hodes, M., Garralda, M. E., Rose, G., and Schwartz, R. (1999). Maternal expressed emotion and adjustment in children with epilepsy. J. Child Psychol. Psychiatry, 40(7), 1083-1093. Hoie, B., Sommerfelt, K., Waaler, P. E., Alsaker, F. D., Skeidsvoll, H., and Mykletun, A. (2006). Psychosocial problems and seizure-related factors in children with epilepsy. Dev. Med. Child Neurol, 48(3), 213-219. Jacoby, A., and Austin, J. K. (2007). Social stigma for adults and children with epilepsy. Epilepsia, 48 Suppl 9, 6-9. Kim, W. J. (1991). Psychiatric aspects of epileptic children and adolescents. J. Am. Acad. Child Adolesc. Psychiatry, 30(6), 874-886. Lavigne, J. V., and Faier-Routman, J. (1993). Correlates of psychological adjustment to pediatric physical disorders: a meta-analytic review and comparison with existing models. J. Dev. Behav. Pediatr, 14(2), 117-123. Lewis, M. A., Salas, I., de la Sota, A., Chiofalo, N., and Leake, B. (1990). Randomized trial of a program to enhance the competencies of children with epilepsy. Epilepsia, 31(1), 101-109. Li, X., Sundquist, J., and Sundquist, K. (2008). Socioeconomic and occupational risk factors for epilepsy: a nationwide epidemiological study in Sweden. Seizure, 17(3), 254-260. Long, C. G., and Moore, J. R. (1979). Parental expectations for their epileptic children. J. Child Psychol. Psychiatry, 20(4), 299-312. Lothman, D. J., and Pianta, R. C. (1993). Role of child-mother interaction in predicting competence of children with epilepsy. Epilepsia, 34(4), 658-669.
Psychosocial Adjustment in Children with Epilepsy and Their Families
245
Miller, V., Palermo, T. M., and Grewe, S. D. (2003). Quality of life in pediatric epilepsy: demographic and disease-related predictors and comparison with healthy controls. Epilepsy Behav, 4(1), 36-42. Minuchin, S., Baker, L., Rosman, B. L., Liebman, R., Milman, L., and Todd, T. C. (1975). A conceptual model of psychosomatic illness in children. Family organization and family therapy. Arch. Gen. Psychiatry, 32(8), 1031-1038. Nicholas, K. K., and Pianta, R. C. (1994). Mother–child interactions and seizure control: Relations with behavior problems in children with epilepsy. Journal of Epilepsy, 7(2), 102-107. Otero, S. (2009). Psychopathology and psychological adjustment in children and adolescents with epilepsy. World J. Pediatr, 5(1), 12-17. Otero, S., and Hodes, M. (2000). Maternal expressed emotion and treatment compliance of children with epilepsy. Dev. Med. Child Neurol, 42(9), 604-608. Ott, D., Caplan, R., Guthrie, D., Siddarth, P., Komo, S., Shields, W. D., Sankar, R., Kornblum, H. and Chayasirisobhon, S. (2001). Measures of psychopathology in children with complex partial seizures and primary generalized epilepsy with absence. J. Am. Acad. Child Adolesc. Psychiatry, 40(8), 907-914. Ott, D., Siddarth, P., Gurbani, S., Koh, S., Tournay, A., Shields, W. D. and Caplan, R. (2003). Behavioral disorders in pediatric epilepsy: unmet psychiatric need. Epilepsia, 44(4), 591597. Pianta, R. C., and Lothman, D. J. (1994). Predicting behavior problems in children with epilepsy: child factors, disease factors, family stress, and child-mother interaction. Child Dev, 65(5), 1415-1428. Plioplys, S., Dunn, D. W., and Caplan, R. (2007). 10-year research update review: psychiatric problems in children with epilepsy. J. Am. Acad. Child Adolesc. Psychiatry, 46(11), 1389-1402. Powers, S. W., Byars, K. C., Mitchell, M. J., Patton, S. R., Standiford, D. A., and Dolan, L. M. (2002). Parent report of mealtime behavior and parenting stress in young children with type 1 diabetes and in healthy control subjects. Diabetes Care, 25(2), 313-318. Rantanen, K., Timonen, S., Hagstrom, K., Hamalainen, P., Eriksson, K., and Nieminen, P. (2009). Social competence of preschool children with epilepsy. Epilepsy Behav, 14(2), 338-343. Raty, L. K., Wilde Larsson, B. M., and Soderfeldt, B. A. (2003). Health-related quality of life in youth: a comparison between adolescents and young adults with uncomplicated epilepsy and healthy controls. J. Adolesc. Health, 33(4), 252-258. Ritchie, K. (1981). Research note: interaction in the families of epileptic children. J. Child Psychol. Psychiatry, 22(1), 65-71. Rodenburg, R., Marie Meijer, A., Dekovic, M., and Aldenkamp, A. P. (2006). Family predictors of psychopathology in children with epilepsy. Epilepsia, 47(3), 601-614. Rodenburg, R., Meijer, A. M., Dekovic, M., and Aldenkamp, A. P. (2005). Family factors and psychopathology in children with epilepsy: a literature review. Epilepsy Behav, 6(4), 488-503. Rodenburg, R., Stams, G. J., Meijer, A. M., Aldenkamp, A. P., and Dekovic, M. (2005). Psychopathology in children with epilepsy: a meta-analysis. J. Pediatr Psychol, 30(6), 453-468.
246
Soraya Otero-Cuesta and Amador Priede
Rutter, M., Yule, W., Graham, P. (1970). A neuropsychiatric study in childhood. (Clinics in development medicine). London: Heineman Medicine. Sbarra, D. A., Rimm-Kaufman, S. E., and Pianta, R. C. (2002). The behavioral and emotional correlates of epilepsy in adolescence: a 7-year follow-up study. Epilepsy Behav, 3(4), 358-367. Shore, C. P., Austin, J. K., and Dunn, D. W. (2004). Maternal adaptation to a child's epilepsy. Epilepsy Behav, 5(4), 557-568. Shore, C. P., Perkins, S. M., and Austin, J. K. (2008). The Seizures and Epilepsy Education (SEE) program for families of children with epilepsy: a preliminary study. Epilepsy Behav, 12(1), 157-164. Siianpää, M. (1973). Medico-social prognosis of children with epilepsy: epidemiological study and analysis of 245 patients. Acta Paediatrica Scandinavica, 62(237), 3-104. Stores, G., and Piran, N. (1978). Dependency of different types in schoolchildren with epilepsy. Psychol. Med, 8(3), 441-445. Streisand, R., Swift, E., Wickmark, T., Chen, R., and Holmes, C. S. (2005). Pediatric parenting stress among parents of children with type 1 diabetes: the role of self-efficacy, responsibility, and fear. J. Pediatr Psychol, 30(6), 513-521. Wallander, J. L., and Varni, J. W. (1998). Effects of pediatric chronic physical disorders on child and family adjustment. J. Child Psychol. Psychiatry, 39(1), 29-46. Williams, J., Steel, C., Sharp, G. B., DelosReyes, E., Phillips, T., Bates, S., Lange, B. and Griebel, M. L. (2003). Parental anxiety and quality of life in children with epilepsy. Epilepsy Behav, 4(5), 483-486. Wood, B. L. (1994). One articulation of the structural family therapy model: a behavioural family model of chronic illness in children. Journal of Family Therapy, 16 53-72.
In: Society, Behaviour and Epilepsy Editors: Jaya Pinikahana and Christine Walker
ISBN 978-1-61761-001-1 © 2011 Nova Science Publishers, Inc.
Chapter XIV
Perspectives on Depression in Epilepsy Adrian Palomino 1and Alexander W. Thompson 2
1. University of California at Davis, Department of Internal Medicine 2. Department of Psychiatry, Texas A & M College of Medicine; Scott and White Hospital, Temple, TX
Abstract Depression in people with epilepsy is a public health problem. Depression is a major determinant of quality of life, leads to less effective self care and medication noncompliance, and is a risk factor for suicide. Depression is common in epilepsy and is often unrecognized and untreated. Viewed entirely from a disease perspective, one solution to the problem of depression in epilepsy entails patient diagnosis using DSM-IVTR criteria and biologically based treatment with antidepressant medication. Unfortunately, a pure disease view of depression in epilepsy ignores major factors that may contribute to low mood. An often used model for understanding psychiatric disorders is the ―biopsychosocial‖ model described by Engel in the 1970‘s. Criticisms of the biopsychosocial model include the argument that it is not a model in the scientific sense of the term and is not clearly defined either by Engel or modern psychiatry. As a method of clinical formulation, then, it may fall short as a way of guiding treatment considering the many complex, interconnected factors (e.g. seizures, seizure medications, cognitive dysfunction, inability to drive, limited physical activity, professional discrimination, and social stigma) present in a depressed person with epilepsy. In this chapter, in addition to discussing the biopsychosocial model, we discuss another approach for understanding mental disorders and guiding treatment decisions. This four perspective approach describes a method of organizing clinical information from disease, dimensional, behavioral, and life story perspectives. Each perspective is supported by its Correspondence: Alexander W. Thompson MD., Texas AandM College of Medicine, Scott and White Hospital, STC-1, 2401 S. 31st St. Temple, TX 76508. 254-724-3214 (o) 254-724-3219 (f). E:mail:
[email protected].
248
Adrian Palomino and Alexander W. Thompson own reasoning and treatment decisions differ depending on the perspective from which a problem is viewed. Developing a clear psychiatric formulation to guide the treatment of a person with a mental disorder, such as a depressed person with epilepsy, requires the consideration of each perspective.
Introduction Consideration of the social aspects of epilepsy warrants close attention to the role of depressed mood in those suffering from epilepsy. Nearly 2500 years ago, Hippocrates commented on the relationship between melancholia and epilepsy. Today, the complex relationship between the two conditions remains a rich area of research as well as a commonplace co-morbidity in psychiatry and neurology clinics alike. Depression is the most common psychiatric disorder in persons with epilepsy (PWE), with an estimated prevalence of between 20-55% in those with uncontrolled seizures and 39% in those with controlled epilepsy (Kanner 2003; Barry et al. 2007). Depression in epilepsy is a major determinant of quality of life (Boylan et al. 2004) and may lead to less effective self-care and medication noncompliance (Gehi et al. 2005). PWE have a rate of suicide higher than the general population (Jones et al. 2003; Christensen et al. 2007), and PWE who complete suicide have higher rates of co-morbid psychiatric illness (Nilsson et al. 2002; Jones et al. 2003), making depression a risk factor for suicide in PWE. Interestingly, research suggests that depression may be a risk factor for developing epilepsy (Hesdorffer et al. 2000). From an economic view, PWE and co-morbid depression have greater health resource utilization than non-depressed PWE (Cramer et al. 2004). In the context of a wordwide epilepsy population of at least 50 million, depression in those with epilepsy is a public health problem. Unfortunately, most people with epilepsy and depression do not have the depression diagnosed or adequately treated (O'Donoghue et al. 1999; Wiegartz et al. 1999; Boylan et al. 2004; Jones et al. 2005). Research details a complex array of factors associated with depression in epilepsy, including being male (Kogeorgos et al. 1982; Altshuler et al. 1990; Septien et al. 1993), having a low IQ or learning disability (Lund 1985), having an ―external locus of control‖ (Hermann et al. 1989), having a family history of major depression (Hermann et al. 1989), and being less physically active (Roth et al. 1994; McAuley et al. 2001). Patients with epilepsy experience stigma in social and vocational areas of life (Jacoby et al. 2007). Research has described stigma as a risk factor for the development of depression (Hermann et al. 1990). There are factors directly related to the epilepsy that are also associated with the development or presence of depression. For example, patients with seizures stemming from a left-sided focus may be at higher risk for depression (Mendez et al. 1986; Altshuler et al. 1990; Indaco et al. 1992; Septien et al. 1993). It is also apparent that those with more frequent seizures appear more likely to develop depression (Trostle et al. 1989; Roth et al. 1994). People with epilepsy who need to take more than one anti-epileptic drug (AED) seem more likely to develop depression and there is an association with certain AEDs such as phenobarbital and the development of a depressive disorder (Barry et al. 2007). Evaluating and treating depression in the complex environment of epilepsy is an intellectual and clinical challenge. Psychiatry as a field has addressed complex issues by embracing a ―biopsychosocial‖ model of understanding mental disorders. For reasons we will
Perspectives on Depression in Epilepsy
249
address, this model has been described as clinically unproductive and encouraging of an eclecticism that does not provide intellectual clarity or advance clinical care. In addition to discussing the biopsychosocial model, we will discuss another approach for understanding mental disorders and guiding treatment decisions. ―Perspectives on Depression in Epilepsy‖ is a direct reference to the text, The Perspectives of Psychiatry, written by Paul McHugh and Philip Slavney (McHugh et al. 1998). This text outlines four perspectives that should be considered when addressing patients with mental disorders: disease, dimension, behavior, and life story. One perspective is not sufficient, nor will it ever be sufficient, for understanding and guiding the treatment of psychiatric disorders. No perspective is superior. Developing a clear psychiatric formulation to guide the treatment of a person with a mental disorder, such as a depressed person with epilepsy, requires the consideration of each perspective.
The Biopsychosocial Model The term ―biopsychosocial,‖ although most commonly associated with George Engel, was first used by Roy Grinker in the 1950s. Grinker, trained as a neurologist and psychiatrist, was also one of Freud‘s last analysands. Reacting to the dominant psychoanalytic orthodoxy of the time, he proposed the term to emphasize the importance of biologic concerns in an era when most psychiatrists were focused on the psychological (Ghaemi 2010). George Engel, in contrast, was an internist who had also trained in psychoanalysis. Engel sensed a need to interject ―human factors‖ into the rigid, reductionist scientific methodology of biologically-based medicine (McLaren 1998). He adopted von Bertalanffy‘s General Systems Theory (GST), which theoretically allowed for scientific exploration across different levels of hierarchy. Using GST as his theoretical backbone, he proposed a biopsychosocial model that would enable ―the physician to extend application of the scientific method to aspects of everyday practice and patient care which was not deemed accessible to the scientific approach‖ (McLaren 1998). In his seminal 1977 paper, Engel concluded that ―the proposed biopsychosocial model provides a blueprint for research, a framework for teaching, and a design for action in the real world of health care‖ (Engel 1977). In a later paper, Engel applied his model to the case of a man with myocardial infarction. In neither paper did Engle describe the applicability or relevance of his model towards mental illness; rather, its applicability was assumed. There are several weaknesses to the biopsychosocial model as put forth by Engel. First, as convincingly argued by McLaren, it is not a model at all (McLaren 1998). A model allows the empirical testing of a theory. A theory, meanwhile, has predictive value. Engel‘s model, in contrast, is based not on theory but on an intuitively pleasing idea: in the setting of illness, the biologic, psychological, and social concerns interact and are relevant. As to how and when they interact, the model is silent. Relatedly, it makes no predictive statements. Second, the ―model‖ gives no guidance on the relative importance of the three tiers, the biologic, social, and psychological. The result, as aptly described by Ghaemi (2010), is a devolution into eclecticism, where clinicians practice according to their personal biases and prejudices. Third, in the three decades or so since its widespread adoption by American psychiatry, there is little or no evidence to suggest that it results in superior treatment outcomes compared to
250
Adrian Palomino and Alexander W. Thompson
biologic or psychotherapeutic reductionism, or other methods of conceptualizing psychiatric care (Ghaemi 2010). Other authors, including McHugh and Slavney (1998), and Ghaemi (2010), have proposed alternatives to the biopsychosocial model. McHugh and Slavney, in particular, have provided a detailed description of a psychiatric method which they term the ―perspectives‖ and describe in their text, The Perspectives of Psychiatry (McHugh et al. 1998).
The Perspectives on Depression in Epilepsy Disease. The disease perspective assumes that certain psychiatric disorders (e.g. melancholic major depression, bipolar disorder, schizophrenia, panic disorder, and obsessive compulsive disorder) result from pathologic cerebral physiology. It is explicitly biomedical. The disease perspective views depression (diagnosed by clinical interview identifying well known cardinal features) as a manifestation of underlying abnormalities in the brain (Gilliam et al. 2004). It aims for cure much like the eradication of a staphylococcus infection or the removal of an inflamed appendix. A clinical example would be the patient with no medical, personality, or substance use disorder who develops melancholia (now called a major depressive episode). He may note the development of low mood, pathological guilt, low self attitude, and vegetative changes such as loss of appetites for food and sex and very poor sleep and energy. This syndrome of melancholia, never present before, may present fairly quickly with no obvious precipitants and result in significant social and occupational dysfunction. Treatment is initiated with an antidepressant with full recovery in four to six weeks. Another example is the development of catatonia as part of a mood disorder that is resolved completely with a course of electroconvulsive therapy. One major difficulty facing psychiatry (and a battle cry for those opposed to psychiatry in general) is the lack of clear-cut pathologic neurochemistry. Regardless, the disease model is an extremely useful perspective when addressing psychiatric problems in those with neurologic disorders like epilepsy or Parkinson‘s Disease. When neurologic injury is present, the signs and symptoms of psychiatric disorder may be so clearly related to the neurologic dysfunction that the suggestion of any other cause makes little sense. Studies describing biological linkages between epilepsy and depression support a disease perspective. A history of major depression is associated with an increased risk for developing unprovoked seizures, suggesting a common underlying neurologic susceptibility (Hesdorffer et al. 2000). In animal models of epilepsy, deficits in both 5-hydroxy tryptophan (5-HT, serotonin) and noradrenaline have been implicated. Rat data showed a positive correlation between noradrenaline and 5-HT deficits and seizure severity (Garcia-Morales et al. 2008). PET imaging has demonstrated 5-HT receptor binding abnormalities in regions distinct from seizure loci (Gilliam 2005). Biological treatments have been found effective in the treatment of depression in people with epilepsy. Some evidence supports the use of selective serotonin reuptake inhibitors in the treatment of depression in epilepsy and suggests such treatment may decrease seizure frequency (Kanner et al. 2000; Kondziella et al. 2009).
Perspectives on Depression in Epilepsy
251
Dimension. The dimensional perspective addresses intelligence and personality. This perspective assumes that certain disorders of mental life may stem from someone‘s underlying cognitive capacity or character traits, features that exist on a dimension for all human beings and have been present for the majority of adult life. Intelligence and other cognitive characteristics can be measured with neuropsychological testing. Personality features such as neuroticism, extraversion, and psychoticism (the dimensions of personality described by Hans Eysenck in the 1940s (Eysenck 1998)) can be determined through detailed interview and objective personality assessment tools. An example of a problem requiring a dimensional perspective is the presentation of anxiety, low mood, and self loathing in a young man with borderline intellectual functioning who is failing in academic pursuits that exceed his capabilities. Another example is the presentation of many years of low mood and mood instability in a woman with a history of sexual abuse, eating disorder, and self injury in the context of relationship stress. In both of these cases, there are mental symptoms present and the potential for psychiatric intervention. But, it should be apparent that the presumption of a neurochemical ―broken part‖ or hope for cure with medication is not the perspective to take when formulating a care plan. A conceptual model of dimensional disorders is: potential, provocation, response. A person‘s dimensional characteristics represent potential, while life events provoke affective or behavioral responses. When assisting a person with dimensional disorders, the goal is guidance toward productive ways of understanding and responding to inevitable life stress. Medications may be used in the management of dimensional disorders, but it is done with the goal alleviating symptoms rather than resolving the condition. A dimensional perspective can be very helpful when evaluating patients with epilepsy. Patients with epilepsy commonly experience cognitive problems that affect treatment compliance, work, and relationships. Long standing changes in personality are described in epilepsy and impact the way interpersonal problems and environmental stresses are handled. Research has shown that certain personality attributes may contribute to depression in a person with epilepsy. In a group of patients with poorly controlled temporal lobe epilepsy, Herman et al (1996) found a strong association between having a pessimistic attributional style and reporting depressive symptoms (Hermann et al. 1996). One study examined 85 adults who had a first seizure. Those reporting a more pervasive sense of losing control had a much greater need for psychological care (Velissaris et al. 2007). Wilson et al (2009) reported on the dimensional assessments of patients with intractable epilepsy. They noted that patients with the onset of epilepsy in adolescence had higher neuroticism in adulthood. Also, those with high neuroticism were more likely to report low mood (Wilson et al. 2009). Behavior. Behaviors are goal-directed actions such as sleeping, eating, having sex, taking medication, drinking beer, and mimicking illness. Disorders of behavior are marked by what a patient does compared to the disease perspective examining what a patient has, or the dimensional perspective addressing who a person is. A classic motivated behavioral disorder is the repeated consumption of alcohol to the point of complete personal, social, physical, and mental destruction. The motivated portion of a motivated behavioral disorder refers to the internal drive (e.g. craving a drink after work) that becomes present or may have always seemed present. In response to the motivation, a person chooses to engage in a behavior (drinking to intoxication) that may or may not be reinforced by a combination of internal and external responses. There is conditioned learning in this setting and a cycle of behavior continues that can result in significant problems. No doubt, there are biological factors
252
Adrian Palomino and Alexander W. Thompson
playing a role in such disorders and these are addressed with biological treatments (like medications that reduce the craving for alcohol or tobacco). But, that does not define a disorder as a disease. Treating a behavioral disorder may involve addressing the internal motivation, the choice or behavior itself, or the social factors perpetuating the behavior. The goal of treatment is to help the patient understand the behavioral problem, stop the behavior, and find reinforcements to encourage the continued avoidance of the behavior. While being depressed involves behavioral changes (e.g. eating, sleeping, and activity change) major depression is not a behavioral disorder, per se. Two important behaviors to consider in a depressed person with epilepsy are substance use and medication compliance. One recent study sought to determine the lifetime risk of seizures in those abusing substances, primarily alcohol and opiates. 626 patients were studied, mostly men. About 9% of the subjects reported seizures and 97% of those who reported a seizure were also dependent on tobacco (Mattoo et al. 2009). While we did not find specific studies addressing the relationship of comorbid substance abuse, depression, and epilepsy, it is well known that substance abuse is often associated with mood disorders and may be a risk factor in the development of depression. People with epilepsy are often noncompliant with antiepileptic drugs (Leppik 1990). Such noncompliance contributes to ongoing epilepsy which is a well described risk factor for depression (Roth et al. 1994; Thompson et al. 2009). In other chronic medical conditions, patients with depression are less compliant with necessary treatments (Gehi et al. 2005). It is likely depression has a similar impact on those with epilepsy. Life Story. The life story perspective may be the most straightforward to grasp. Distressing mood states may be understandable responses given the story of one‘s life. A patient example is illustrative. A 28 year old man with no significant prior mood problems reported depression, when, after an elaborate work-up and surgery to remove a temporal lobe lesion in a hope to cure his partial epilepsy, he started to seize again. Prior to the surgery, he described his hopes for life after epilepsy. While he reported depression, other cardinal features of major depression were not present. In this case, it is not reasonable to suggest that his depression is the expression of a depressive disease. Such a view ignores the experience he has been through and the opportunity to better understand better his hopes, his demoralization, and the ways to move on productively. The life story perspective intimately connects with the other perspectives as a person‘s response to life events (a response that may involve affective changes and abnormal behaviors) depends on the presence of underlying diseases, intelligence, and personality structure. A seizure and epilepsy may bring with them a host of unwanted and un-expected lifestyle changes, including a moratorium on driving and potential restrictions on work, family, and recreational activities (Velissaris et al. 2007). Numerous authors have found that PWE experience more social and environmental problems than the general population. Social isolation, reduced marriageablity, less education, more unemployment and/or underemployment are common (Bandstra et al. 2008). In a survey of 81 adults, the chief concerns about living with epilepsy were driving, independence, work, and embarrassment (Gilliam et al. 1997). Social isolation in PWE is common and multifactorial in origin, stemming from fear of having a seizure in public, reduced opportunities for social interaction in the traditional areas of school and work, inability to drive, and fear of social stigma (McCagh et al. 2009). In a
Perspectives on Depression in Epilepsy
253
prospective trial of 319 adults with epilepsy, a low level of social support was predictive of depressive symptoms along with being unemployed and having felt stigma (Reisinger et al. 2009). Seizure frequency is positively associated with marital status, with increasing seizure frequency associated with a greater likelihood of being divorced or single. Earlier age of onset of epilepsy is positively correlated with not being married (McCagh et al. 2009). Stigma may be either enacted or felt. Enacted stigma encompasses specific instances of discrimination due to having a seizure disorder. It may be overt, such as discrimination in the workplace or job loss, or more subtle, such as social rejection. Felt, or perceived, stigma, is an individual‘s subjective sense of stigmatization, and may be experienced in the absense of enacted stigma (Bandstra et al. 2008). Over sixty percent of PWE experiencing frequent seizures report feeling stigmatized by their disorder (McCagh et al. 2009), and seizure frequency is positively associated with felt stigmatization (Bandstra et al. 2008). In a small study, a psychoeducational CBT-intervention resulted in decreased depressive symptoms and increased psychosocial functioning (Davis et al. 1984). The literature on coping with epilepsy strongly suggests that the engagement-type coping strategies of problem solving and cognitive restructuring (both depicting active, purposeful planning and dealing with stressful situations) were associated with better psychosocial adaptation (Livneh et al. 2001).
Concluding Remarks The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) (American Psychiatric Association 2000) describes specific criteria and time requirements for making psychiatric diagnoses. For the diagnosis of a major depressive disorder, it indicates there must be five of nine symptoms (depressed mood, anhedonia, guilt, thoughts of suicide, sleep disturbance, appetite disturbance, low energy, feeling physically agitated or slowed down, and trouble concentrating) present for most of the time over the past two weeks with at least one symptom being depressed mood or anhedonia. The DSM adds that the disturbance cannot be accounted for by another psychiatric disorder (like bipolar disorder) or the effects of a medical condition, prescribed medication, or abusable substance. By detailing this structure for diagnosing depression, the DSM has operationalized criteria for a mood disease, major depression. A major problem, however, is that the DSM-IV criteria for disorders such as major depression simply are not that reliable or valid (Taylor et al. 2009). This becomes apparent in people with neurological disorders like epilepsy where many of the specified symptoms may not be present (despite the presence of a real mood disorder) or many symptoms (like trouble with sleep, energy, or concentration) may be the results of the underlying condition or medication rather than a mood disorder. Many patients will present with an atypical clinical picture that fails to meet DSM-IV criteria for major depression (Kanner 2003; Gilliam 2005). Kraeplin, writing in the 1920‘s, described an intermittent and pleomorphic dysphoric disorder. This condition has been referred to as the ―interictal dysphoric disorder‖ and is characterized by symptomatic periods of depressed mood, irritability, anxiety, phobic fear, anergia, pain, and occasional euphoric mood (Blumer et al. 2004). Symptomatic periods may last from hours to days, followed by a similar period
254
Adrian Palomino and Alexander W. Thompson
free of symptoms. Kanner (2003) notes that depressive symptoms may also mimic a dysthymic disorder, though the intermittent, interrupted frequency of the symptoms confounds a diagnosis based upon DSM-IV criteria (Kanner 2003). Other authors have reported large numbers of patients having atypical or ―not otherwise specified‖ mood disorders (Gilliam 2005). The point of this is that strict disease reasoning based on DSM-IV criteria is not the most effective way of identifying depressive disorders in people with epilepsy. Formulation and Treatment. A major depressive disorder should be diagnosed in a person with epilepsy when there is a discrete change in mood combined with change in self attitude, psychomotor changes, and vegetative disturbance (sleeping, eating, and sexual activity changes). This diagnosis must be part of a formulation that gives consideration to details of the patient‘s personality and intelligence, behaviors, and life story. Each area must be systematically assessed in a detailed interview; only then can appropriate intervention proceed. When it is apparent that a depressive mood disease is the major factor present, a cut and dry biological treatment approach may suffice. In most other situations, psychotherapy and behavioral interventions will be necessary to help guide, redirect, and support the person suffering from epilepsy and depression.
References Altshuler, L. L., O. Devinsky, et al. (1990). "Depression, anxiety, and temporal lobe epilepsy. Laterality of focus and symptoms." Arch. Neurol 47(3): 284-8. American Psychiatric Association (2000). Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision. Washington, DC, American Psychiatric Association. Bandstra, N. F., C. S. Camfield, et al. (2008). "Stigma of epilepsy." Can. J. Neurol. Sci. 35(4): 436-40. Barry, J. J., A. Lembke, et al. (2007). Affective Disorders in Epilepsy. Psychiatric Issues in Epilepsy, Second Edition. A. Ettinger and A. Kanner. Philadelphia, PA, Lippincott Williams and Wilkins: 203-247. Blumer, D., G. Montouris, et al. (2004). "The interictal dysphoric disorder: recognition, pathogenesis, and treatment of the major psychiatric disorder of epilepsy." Epilepsy Behav. 5(6): 826-40. Boylan, L. S., L. A. Flint, et al. (2004). "Depression but not seizure frequency predicts quality of life in treatment-resistant epilepsy." Neurology 62(2): 258-61. Christensen, J., M. Vestergaard, et al. (2007). "Epilepsy and risk of suicide: a populationbased case-control study." Lancet Neurol 6(8): 693-8. Cramer, J. A., D. Blum, et al. (2004). "The impact of comorbid depression on health resource utilization in a community sample of people with epilepsy." Epilepsy Behav. 5(3): 33742. Davis, G. R., H. E. Armstrong, Jr., et al. (1984). "Cognitive-behavioral treatment of depressed affect among epileptics: preliminary findings." J. Clin. Psychol. 40(4): 930-5. Engel, G. L. (1977). "The need for a new medical model: a challenge for biomedicine." Science 196(4286): 129-36.
Perspectives on Depression in Epilepsy
255
Eysenck, H. (1998). Dimensions of Personality. New Brunswick, Transaction Publishers. Garcia-Morales, I., P. de la Pena Mayor, et al. (2008). "Psychiatric comorbidities in epilepsy: identification and treatment." Neurologist 14(6 Suppl 1): S15-25. Gehi, A., D. Haas, et al. (2005). "Depression and medication adherence in outpatients with coronary heart disease: findings from the Heart and Soul Study." Arch. Intern. Med. 165(21): 2508-13. Ghaemi, S. N. (2010). The Rise and Fall of the Biopsychosocial Model. Baltimore, The Johns Hopkins University Press. Gilliam, F., R. Kuzniecky, et al. (1997). "Patient-validated content of epilepsy-specific quality-of-life measurement." Epilepsia 38(2): 233-6. Gilliam, F. G. (2005). "Diagnosis and treatment of mood disorders in persons with epilepsy." Curr. Opin. Neurol. 18(2): 129-33. Gilliam, F. G., J. Santos, et al. (2004). "Depression in epilepsy: ignoring clinical expression of neuronal network dysfunction?" Epilepsia 45 Suppl 2: 28-33. Hermann, B. P., M. R. Trenerry, et al. (1996). "Learned helplessness, attributional style, and depression in epilepsy. Bozeman Epilepsy Surgery Consortium." Epilepsia 37(7): 680-6. Hermann, B. P. and S. Whitman (1989). "Psychosocial predictors of depression in epilepsy." Journal of Epilepsy(2): 231-7. Hermann, B. P., S. Whitman, et al. (1990). "Psychosocial predictors of psychopathology in epilepsy." Br. J. Psychiatry 156: 98-105. Hermann, B. P. and A. R. Wyler (1989). "Depression, locus of control, and the effects of epilepsy surgery." Epilepsia 30(3): 332-8. Hesdorffer, D. C., W. A. Hauser, et al. (2000). "Major depression is a risk factor for seizures in older adults." Ann. Neurol. 47(2): 246-9. Indaco, A., P. B. Carrieri, et al. (1992). "Interictal depression in epilepsy." Epilepsy Res. 12(1): 45-50. Jacoby, A. and J. K. Austin (2007). "Social stigma for adults and children with epilepsy." Epilepsia 48 Suppl 9: 6-9. Jones, J. E., B. P. Hermann, et al. (2005). "Clinical assessment of Axis I psychiatric morbidity in chronic epilepsy: a multicenter investigation." J. Neuropsychiatry Clin. Neurosci. 17(2): 172-9. Jones, J. E., B. P. Hermann, et al. (2003). "Rates and risk factors for suicide, suicidal ideation, and suicide attempts in chronic epilepsy." Epilepsy Behav. 4 Suppl 3: S31-8. Kanner, A. M. (2003). "Depression in epilepsy: prevalence, clinical semiology, pathogenic mechanisms, and treatment." Biol. Psychiatry 54(3): 388-98. Kanner, A. M., A. M. Kozak, et al. (2000). "The Use of Sertraline in Patients with Epilepsy: Is It Safe?" Epilepsy Behav. 1(2): 100-105. Kogeorgos, J., P. Fonagy, et al. (1982). "Psychiatric symptom patterns of chronic epileptics attending a neurological clinic: a controlled investigation." Br. J. Psychiatry 140: 236-43. Kondziella, D. and F. Asztely (2009). "Don't be afraid to treat depression in patients with epilepsy!" Acta Neurol. Scand. 119(2): 75-80. Leppik, I. E. (1990). "How to get patients with epilepsy to take their medication. The problem of noncompliance." Postgrad. Med. 88(1): 253-6. Livneh, H., L. M. Wilson, et al. (2001). "Psychosocial Adaptation to Epilepsy: The Role of Coping Strategies." Epilepsy Behav. 2(6): 533-544.
256
Adrian Palomino and Alexander W. Thompson
Lund, J. (1985). "Epilepsy and psychiatric disorder in the mentally retarded adult." Acta Psychiatr Scand. 72(6): 557-62. Mattoo, S. K., S. M. Singh, et al. (2009). "Prevalence and correlates of epileptic seizure in substance-abusing subjects." Psychiatry Clin. Neurosci. 63(4): 580-2. McAuley, J. W., L. Long, et al. (2001). "A Prospective Evaluation of the Effects of a 12Week Outpatient Exercise Program on Clinical and Behavioral Outcomes in Patients with Epilepsy." Epilepsy Behav. 2(6): 592-600. McCagh, J., J. E. Fisk, et al. (2009). "Epilepsy, psychosocial and cognitive functioning." Epilepsy Res. 86(1): 1-14. McHugh, P. R. and P. R. Slavney (1998). The Perspectives of Psychiatry. Baltimore, The Johns Hopkins University Press. McLaren, N. (1998). "A critical review of the biopsychosocial model." Aust. N. Z. J. Psychiatry 32(1): 86-92; discussion 93-6. Mendez, M. F., J. L. Cummings, et al. (1986). "Depression in epilepsy. Significance and phenomenology." Arch. Neurol. 43(8): 766-70. Nilsson, L., A. Ahlbom, et al. (2002). "Risk factors for suicide in epilepsy: a case control study." Epilepsia 43(6): 644-51. O'Donoghue, M. F., D. M. Goodridge, et al. (1999). "Assessing the psychosocial consequences of epilepsy: a community-based study." Br. J. Gen. Pract. 49(440): 211-4. Reisinger, E. L. and C. DiIorio (2009). "Individual, seizure-related, and psychosocial predictors of depressive symptoms among people with epilepsy over six months." Epilepsy Behav. 15(2): 196-201. Roth, D. L., K. T. Goode, et al. (1994). "Physical exercise, stressful life experience, and depression in adults with epilepsy." Epilepsia 35(6): 1248-55. Septien, L., M. Giroud, et al. (1993). "Depression and partial epilepsy: relevance of laterality of the epileptic focus." Neurol. Res. 15(2): 136-8. Septien, L., P. Gras, et al. (1993). "Depression and temporal epilepsy. The possible role of laterality of the epileptic foci and of gender." Neurophysiol. Clin. 23(4): 327-36. Taylor, M. A. and N. A. Vaidya (2009). Beyond the DSM and ICD. Descriptive Psychopathology. Cambridge, Cambridge University Press: 3-21. Thompson, A. W., J. W. Miller, et al. (2009). "Sociodemographic and clinical factors associated with depression in epilepsy." Epilepsy Behav. 14(4): 655-60. Trostle, J. A., W. A. Hauser, et al. (1989). "Psychologic and social adjustment to epilepsy in Rochester, Minnesota." Neurology 39(5): 633-7. Velissaris, S. L., S. J. Wilson, et al. (2007). "The psychological impact of a newly diagnosed seizure: losing and restoring perceived control." Epilepsy Behav. 10(2): 223-33. Wiegartz, P., M. Seidenberg, et al. (1999). "Co-morbid psychiatric disorder in chronic epilepsy: recognition and etiology of depression." Neurology 53(5 Suppl 2): S3-8. Wilson, S. J., J. M. Wrench, et al. (2009). "Personality development in the context of intractable epilepsy." Arch. Neurol. 66(1): 68-72.
In: Society, Behaviour and Epilepsy Editors: Jaya Pinikahana and Christine Walker
ISBN 978-1-61761-001-1 © 2011 Nova Science Publishers, Inc.
Chapter XV
Depression in People with Epilepsy Elizabeth Reisinger Walker and Colleen DiIorio Department of Behavioral Science and Health Education, Emory University, Atalanta, USA
Abstract Depression is the most frequent psychiatric disorder associated with epilepsy; however it is often under-diagnosed and under-treated. A growing number of investigators have examined the factors associated with depression among people with epilepsy and established the negative effect of depression on quality of life. Thus far, less attention has been paid to the barriers and facilitators for the treatment of depression among people with epilepsy. Individual, provider and system level factors can contribute to the recognition of depression and its treatment. Elucidation of these factors for people with epilepsy is necessary to inform the development of effective interventions to ultimately reduce the burden of depression in this population. In this chapter, we examine the literature on depression and epilepsy including factors influencing the diagnosis and treatment of depression, barriers to treatment, and approaches for treating depression. We will conclude with proposed avenues for future research.
Correspondence: Professor Collen DiIorio PhD, RN, FAAN, Department of Behavioral Science and Health Education, Rollins School of Public Health, Emory University, 1518 Clifton Road, NE, Atlanta, GA, USA. Tele: 404-727-8741, Fax: 404-727-1369. Email:
[email protected].
258
Elizabeth Reisinger Walker and Colleen DiIorio
Introduction Depression is the most frequent psychiatric disorder associated with epilepsy; however it is often under-diagnosed and under-treated. A growing number of investigators have examined the factors associated with depression among people with epilepsy and established the negative effect of depression on quality of life. Thus far, less attention has been paid to the barriers and facilitators for treatment of depression among people with epilepsy. Individual, provider, and system level factors can contribute to the recognition of depression and its treatment. Elucidation of these factors for people with epilepsy is necessary to inform the development of effective interventions to ultimately reduce the burden of depression in this population. In this chapter, we examine the literature on depression and epilepsy including the factors influencing the diagnosis and treatment of depression, barriers to treatment, and approaches for treating depression. We will conclude with proposed avenues for future research.
Depression Depression affects a significant portion of the world‘s population. Currently, unipolar depressive disorder is the fourth leading cause of disease burden in the world, representing 4.4% of disability adjusted life years or years living with a disability (Ustun et al, 2004). Hasin and colleagues (2005) reported that lifetime prevalence (the number of individuals, at assessment, who experienced depression, compared to the total number of individuals in that population) of major depressive disorder (MDD) ranges from 1.5% to 19%, with a mean of 8.8% across 11 countries. The lifetime prevalence in the United States and European countries is at the higher end of the continuum ranging from 13% to 19% (Hasin, et al., 2005). Lower lifetime prevalence rates are reported in Taiwan (1.5%), Korea (2.9%; Weissman, et al., 1996), Chile (9.7%; Vicente, et al., 2006), and South Africa (9.7%; Tomlinson et al, 2009). Comparisons of depression prevalence across nations, particularly developing countries, is often difficult because of the lack of nationally representative epidemiologic studies (Tomlinson, et al., 2009).
Etiology The etiology of depression is not totally understood. However, most clinicians and researchers believe that a combination of genetic, physiologic, and environmental factors contribute to the onset of depression. Although no specific depression gene has been identified, evidence suggests that there may be a genetic component present in at least some cases of depression. For example, identical twins are more likely to share the diagnosis of depression than are fraternal twins (Sullivan et al., 2000), and family history of depression has been associated with severe postpartum disorder (Scrandis et al, 2007). Researchers believe that an imbalance in the production or uptake of neurotransmitters plays a role in depression. Neurotransmitters that have been studied in this regard include dopamine, gamma-aminobutyric acid (GABA) and serotonin. The serotonergic system has been the
Depression in People with Epilepsy
259
focus of significant study. An imbalance in serotonin levels in the brain due to low production or problems with receptor cells has been linked with changes in mood and symptoms of depression, and recently, Svenningsson and colleagues (2006) identified a serotonin transporter gene that is associated with depression-like states. Evidence for a physiologic component of depression is also based on descriptive studies of individuals with neurologic disorders. Major depression is common among men and women suffering strokes and those diagnosed with epilepsy, Huntington‘s and Parkinson‘s disease among others (Langlieb and DePaulo, 2008). Although the causal mechanism is currently not known, researchers suggest that changes in brain structure or neurotransmitter levels due to the chronic condition may contribute to depression (Swinkels et al., 2005). Life events that are considered stressful have been widely implicated as a precipitant of depression. Childhood abuse, maltreatment, loss, job-related stressors, and traumatic events can leave individuals vulnerable to subsequent depressive episodes. People perceive and interpret these and other stressors differently. For some people, persistent or chronic stress may increase the risk of developing mental distress, mood changes, or a major depressive episode. The risk can be moderated by supportive resources and coping skills.
Symptoms of Depression Symptoms of depression include sadness, diminished interest and pleasure in everyday events, changes in appetite, trouble sleeping, fatigue, feelings of worthlessness, and inability to concentrate (Mensah et al, 2006). Depressed individuals also report episodes of tearfulness or crying, weight gain or loss, low energy and productivity, restlessness or irritability, and in more severe cases, thoughts of death and suicide. To be diagnosed with MDD, a person must experience depressed mood and loss of interest or pleasure in daily activities for at least two weeks (American Psychiatric Association, 2000). Interestingly, most depressed individuals are likely to consult a doctor for medical complaints such as headaches, fatigue, pain, and gastrointestinal symptoms rather than for psychiatric symptoms. Medical symptoms without identified pathology often connote some degree of psychological distress (Seelig and Katon, 2008). Simon (1991) found that people who reported five or more unexplained symptoms were also found to have psychiatric disorders. The experience of depression can vary across different cultural contexts. Some cultures and languages do not have a conceptualization or term for depression (Lehti et al., 2009). In other societies, depression may not be as strongly associated with mood change as it is in Western medicine (Patel, 2001). For example, people may complain of nerves, discomfort, weakness, or pain rather than psychological distress (American Psychiatric Association, 2000; Kleinman, 2004). Additionally, prolonged episodes of grief or sadness may be considered to be depression by diagnostic standards, but represent a culturally appropriate response to the individual. Cultural context also impacts an individual‘s decision to seek treatment, perceptions on what type of treatment is appropriate, and interactions with health care providers (Kleinman, 2004).
260
Elizabeth Reisinger Walker and Colleen DiIorio
Outcomes Depression has a negative effect on nearly all aspects of life, including health, relationships, functioning, and overall quality of life (Strine, et al., 2009). Research shows that people who are diagnosed with depression are at a higher risk for chronic disease, disability and mortality (Barth et al, 2004; Cuijpers and Smit, 2002). In a comparison of nondisabled elderly individuals with and without depression, the depressed individuals were significantly more likely to develop a physical disability (Penninx et al, 1999). In a metaanalysis of depression and excess mortality, Cuijpers and Smit (2002) found that increased risk for disability exists even among people who exhibit subclinical forms of depression, as well as among those with MDD. The negative impact of depression in the work environment is greater than other types of chronic illnesses including cancer and heart disease. Persistent job-related stress and other life events can lead to depression among vulnerable workers. Depressed workers display a number of negative work habits compared to their nondepressed counterparts (Lerner and Henke, 2008). Depressed workers are more likely to complain of somatic symptoms such as headaches, pain and fatigue leading to a greater number of visits to the doctor and more sick days. During work hours, depressed workers demonstrate lower productivity (called presenteeism) due to these somatic complaints as well as and maybe more importantly the inability to concentrate and the loss of interest in work (Donohue and Pincus, 2007). Inattention leads to higher rates of occupational injuries among those who are depressed, and poor collegial relationships lead to less cooperation and more arguments. Workers, like others who are depressed, tend to self-medicate and may use more alcohol and drugs, a practice which compounds depression-related work site problems. Subsequently, depressed workers are more likely to lose their jobs and to remain unemployed compared to non-depressed colleagues. The impact of depression in the workplace, especially when combined with other chronic diseases, is extremely costly. Employers pay more in health care costs for employees with depression and other conditions compared to employees with medical conditions alone (Druss et al., 2000). People with depression and chronic disease report significantly more ambulatory and emergency room visits, days absent from work, and days spent in bed compared to people with chronic disease but no depression (Egede, 2007). Effective treatment of depression, however, can significantly improve employee productivity (Simon, et al., 2001). Depression also has a negative association with marital satisfaction and the quality of interpersonal relationships. People who are depressed tend to have relationships characterized by more negative interactions, including hostility and conflict, and fewer positive interactions compared to those who are non-depressed (Rehman et al., 2008; Zlotnick et al, 2000). Greater interpersonal difficulty is usually reported in relationships with spouses or partners than friends or strangers, possibly because intimate relationships involve closer and more frequent contact than other relationships (Zlotnick, et al., 2000). In a longitudinal study among people with renal disease and their spouses, Pruchno and colleagues (2009) showed that the depressive symptoms of both patients and spouses were associated with their marital satisfaction. They indicate that the relationship between depressive symptoms and marital satisfaction may be bidirectional (Pruchno, et al., 2009). The complex nature of this relationship is highlighted by the findings of Fincham and colleagues (1997) who found that depressive symptoms predict marital satisfaction in men, and marital satisfaction predicts depressive symptoms in women.
Depression in People with Epilepsy
261
Epilepsy and Depression Prevalence People with chronic conditions are at particular risk for depression, including people with epilepsy (Hermann et al., 2000; Kanner, 2003). Epilepsy is one of the most common neurological disorders, and is characterized by recurrent seizures caused by abnormal electrical activity in the brain (Centers for Disease Control and Prevention, 2007). An estimated 50 million people in the world are affected by epilepsy, 80% of whom live in developing countries. Prevalence rates of active epilepsy vary across countries, but generally fall between 5 and 10 cases per 1,000 people (Scott, Latoo, and Sander, 2001). Higher prevalence rates, which may include both active and inactive cases of epilepsy, have been reported in some areas, including Latin America (17.8/1,000; Burneo et al, 2005) and Africa (10-20/1,000; Diop et al, 2003). The burden of epilepsy is felt by both individuals with the condition and society as a whole. Although many people can control their seizures with antiepileptic medication, at least 30% of people do not respond to treatment (Centers for Disease Control and Prevention, 2007). In developing countries, people with epilepsy often have difficulties receiving adequate treatment and obtaining needed antiepileptic medication (Scott, et al., 2001). Individuals with epilepsy report lower educational attainment, greater activity restriction, lower quality of life and increased healthcare service use compared to the general population (Wiebe et al, 1999). Adults with epilepsy report more mental, physical, and overall unhealthy days than those without epilepsy (Centers for Disease Control and Prevention, 2005; Kobau, et al., 2004). Also, 64% of people with active epilepsy report some form of disability, or limitation in their activities, compared with 18% of the general population (Centers for Disease Control and Prevention, 2005). The impact on society is reflected in the estimate that, in the United States, $15.5 billion are lost each year in medical costs and reduced earnings and productivity due to epilepsy (Centers for Disease Control and Prevention, 2007).
Chronic Disease Depression is often associated with chronic diseases and is the most common psychiatric disorder associated with epilepsy (Barry and Jones, 2005; Boylan, et al., 2004; Jones et al., 2005). The lifetime rate of depression among people with epilepsy is estimated to be around 30%, which is elevated compared to the general population (Hermann, et al., 2000). In addition to a high prevalence of depression among persons with epilepsy, the suicide rate of people with epilepsy is about 11.5%, which is ten times higher than among the general population (Jones et al., 2003). Prince and colleagues (2007) proposed three different mechanisms that might explain the link between mental disorders, such as depression, and chronic disease, such as epilepsy. First mental disorders may lead to other chronic diseases, such as cardiovascular disease and diabetes (Eaton et al, 1996; Rugulies, 2002). There is evidence that depression predicts the onset of epilepsy in some cases, though the exact association is currently unknown (Kanner, 2008). Second, chronic conditions may contribute to mental disorders through biological,
262
Elizabeth Reisinger Walker and Colleen DiIorio
psychological, or stress processes. Chronic conditions, especially neurological disorders such as epilepsy, may cause changes in the brain that may lead to depression. Additionally, chronic diseases can be disabling and can result in activity limitations and difficulties with work, finances, and relationships. The stress caused by the symptoms of a chronic disease and the subsequent difficulties may increase a person‘s distress and vulnerability to depression (Haddad, 2009; Vilhjalmsson, 1998). Having a chronic disease can also negatively impact personal resources, such as self-esteem and mastery, which may hinder an individual‘s ability to manage their condition and cope with depressive symptoms (Vilhjalmsson, 1998). Third, the presence of a mental disorder may affect treatment and outcomes of other health conditions. For example, depression contributes to poorer outcomes in chronic diseases, potentially due to biological effects, such as increased inflammation and platelet adhesiveness, or a decrease in self-management and positive lifestyle behaviors (Seelig and Katon, 2008). The interconnections between the potential causes of depression and chronic disease are illustrated by a conceptual model developed by Katon (2003). He suggests that risk factors for depression, including genetic vulnerability, childhood adversity, and stressful life events, might lead to negative behaviors that could foster the onset of chronic disease. For example, childhood adversity is related to risk behaviors such as smoking and overeating, which, in turn, are linked to chronic disease. People who smoke are more likely to develop lung disease, including cancer, whereas those who are obese are more likely to develop heart conditions, diabetes, and hypertension. Additionally, genetic factors may predispose a person to both depression and other health conditions (Katon, 2003).
Symptom Burden There is substantial empirical evidence that the symptom burden and functional impairment from depression adversely affects the health of people with chronic diseases. In a sample from 60 countries, individuals reporting depression had lower overall health scores compared to people with a chronic disease (angina, arthritis, asthma, or diabetes) but no depression. Comorbid depression with one of the four chronic diseases was associated with worse health than depression alone, a chronic disease alone, or a combination of chronic diseases but no depression (Moussavi, et al., 2007). Katon and colleagues (2007) found that patients with comorbid depression or anxiety and chronic disease reported significantly more medical symptoms compared to those with chronic disease alone, even when controlling for disease severity. Many people with chronic disorders, including epilepsy, must adhere to medical and lifestyle regimens in order to manage symptoms and prevent advancement of the disease. Because depression affects physical and mental functional ability (Baune et al., 2007), people with both chronic disorders and depression encounter more difficulties adhering to self-care regimens, which can result in a significant decrease in their health-related quality of life (Katon and Ciechanowski, 2002). Depression has been identified as a barrier to active selfmanagement because individuals feel isolated and unable to cope (Jerant et al., 2005). Additionally, Katon (2003) posits that underlying factors of depression, such as adverse events in childhood, may result in maladaptive attachment, which might prevent successful collaboration with physicians to manage a chronic condition.
Depression in People with Epilepsy
263
Epilepsy and Depression People with epilepsy must deal with the often unpredictable and potentially disabling effects of their seizures. Uncertainty and fear of having a seizure has been indicated as the worst thing about having seizures, followed by activity limitations and cognitive impairment (Fisher, et al., 2000a). Seizure characteristics, such as type (Grabowska-Grzyb et al., 2006; Kimiskidis, et al., 2007; Mendez, Doss, Taylor, and Salguero, 1993; Schmitz et al., 1999), severity (Cramer et al., 2003b; Mensah, et al., 2006), and frequency (Jacoby et al., 1996; Kimiskidis, et al., 2007; Mensah, et al., 2006; Paradiso et al., 2001; Thapar et al., 2005) are associated with higher levels of depression in both community and clinic based populations. People with epilepsy and depression also tend to take more seizure medications (Kimiskidis, et al., 2007; Mendez, et al., 1993) and have more side effects from these medications (Ettinger, Reed, and Cramer, 2004; Mensah, et al., 2006), though not all researchers have found this association (Grabowska-Grzyb, et al., 2006; Paradiso, et al., 2001). Medications taken to control seizures have unwanted side effects that can affect memory and cognition, reduce energy levels, and cause drowsiness (Fisher, et al., 2000b). Seizures can also impair memory and cognitive function, including concentration, forgetfulness, and disorientation. People with epilepsy who experience memory problems tend to be more depressed than those without memory problems (Corcoran and Thompson, 1993; McCagh et al., 2009). Due to the unpredictable nature of seizures, people with epilepsy are more limited in their ability to travel, work, and participate in social activities, leading to social isolation. In some countries, such as the United States, people with active seizures are legally restricted from driving until they are seizure free (Krauss et al., 2001). Although many people with epilepsy are employed, a significant proportion of individuals, across different countries, remain under- or unemployed and have experienced difficulties or prejudice when seeking jobs (Bishop, 2002; Chaplin et al., 1998; Collings and Chappell, 1994). In a literature review, Smeets and colleagues (2007) discuss the multiple factors that affect employment for people with epilepsy, such as level of supportiveness from employers, interference of seizures on job performance, and the impact of epilepsy on educational achievement and subsequently employment. Unemployment can lead to social isolation and feelings of worthlessness (Beran, 1999). Financial stress resulting from unemployment can compound feelings of isolation and lead to frustration and hopelessness. Several studies have shown that unemployment is a predictor of depression among people with epilepsy (Ettinger, et al., 2004; Grabowska-Grzyb, et al., 2006; Mensah, et al., 2006; Reisinger and DiIorio, 2009). Other related factors that contribute to depression among people with epilepsy are low income and financial stress (Ettinger, et al., 2004; Hermann and Whitman, 1989). Additionally, people with epilepsy and depression tend to have less social support (Hermann and Whitman, 1989; Reisinger and DiIorio, 2009) and more concerns about being in social situations (Ettinger, et al., 2004).
Stigma People with epilepsy experience stigma related to their condition, which can impact their psychological well-being and quality of life (Jacoby et al., 2005). Epilepsy is considered to be a stigmatizing disorder because of the unprovoked and unpredictable nature of seizures.
264
Elizabeth Reisinger Walker and Colleen DiIorio
Epilepsy can elicit feelings of fear, concern, and helplessness in others, especially if they do not know much about the condition or do not know what to do in the event of a seizure. Misperceptions about epilepsy, including the ideas that all people with epilepsy experience tonic-clonic seizures and that epilepsy is a mental disorder, still exist and can perpetuate stigma (Jacoby et al., 2004; Jacoby, et al., 2005). Jacoby and colleagues found that knowledge of and favorable attitudes toward epilepsy appear to be most common among individuals familiar with epilepsy, women, those with higher socioeconomic status, and those in a middle-age range (Jacoby, et al., 2004). In a study including respondents from 15 European countries, about half of the people with epilepsy report feeling stigmatized by their condition (Baker et al., 1999). Perceived stigma is associated with having active epilepsy, multiple seizure types, lower education level, greater perceived limitations due to epilepsy, and depression rates (Baker et al., 1997; Jacoby, et al., 2005). The stigma associated with epilepsy also has been shown to impact the self-efficacy needed to manage the condition (DiIorio, et al., 2006) and is linked with lower self-esteem and greater perceived helplessness (Jacoby, et al., 2005). People with epilepsy and depression must also face the added stigma of having a mental illness, which can impact self-esteem and self-efficacy as well (Corrigan et al., 2005).
Quality of Life The severity and number of depressive symptoms experienced by people with epilepsy are strongly related to their self-reported quality of life (Boylan, et al., 2004; Cramer et al., 2003a; Johnson et al., 2004; Loring et al., 2004; Tracy et al., 2006). Among a sample of people with refractory epilepsy, Boylan and colleagues (2004) found that depression, but not seizure frequency, duration, or type, predicted quality of life. Similarly, Loring et al. (2004) showed that depression and seizure worry were the strongest predictors of quality of life. Among clinic or community samples of people with epilepsy, predictors of quality of life include depression (Canuet, et al., 2009; Cramer, et al., 2003a; Johnson, et al., 2004; Szaflarski and Szaflarski, 2004; Tracy, et al., 2006), anxiety (Johnson, et al., 2004), seizure characteristics (control, frequency, or severity; Canuet, et al., 2009; Johnson, et al., 2004; Tracy, et al., 2006), stigma (McLaughlin et al., 2008), and the ability to drive (Tracy, et al., 2006). In each study that included depression, seizure characteristics were less important than depression in explaining quality of life (Canuet, et al., 2009; Cramer, et al., 2003a; Johnson, et al., 2004; Szaflarski and Szaflarski, 2004; Tracy, et al., 2006). Cramer and colleagues found significant differences in reported quality of life scores between individuals with no depression, mild depression, and major depression, with quality of life decreasing with increasing depression severity (Cramer, et al., 2003a). Notably, these findings demonstrate that even mild-to-moderate depression can have a significant influence on quality of life for people with epilepsy.
Depression in People with Epilepsy
265
Factors Influencing the Diagnosis of Depression Depression among people with epilepsy is often undiagnosed and untreated (Barry, 2003; Barry and Jones, 2005; Jones et al., 2005). In two separate studies, only 43% of patients with epilepsy and current major depression were being treated with antidepressants (Jones et al., 2005; Wiegartz et al., 1999). Individual-, provider-, and system-level factors contribute to this lack of recognition and treatment.
Individual-Level Factors According to the depression literature, the individual-level factors that influence people‘s decision to seek help for depression include symptom severity, fear of stigma, willingness to disclose problems, perception of the benefits of treatment, access to care and financial costs (Collins et al. , 2004). People may elect not to seek treatment for depression because they feel they can handle it themselves, it is an expected response to life stress, or that it is due to other chronic conditions (Blumenthal and Endicott, 1996; Goldman et al., 1999). An individual may first try to employ coping strategies before seeking treatment for depressive symptoms. These coping mechanisms may include spirituality, calling on support of family or friends, or more negative responses such as denial. An individual also may recognize the need for treatment, but be unable to access treatment because of lack of availability of mental health professionals who share a similar race or gender, inconvenient location of care, lack of time, or inadequate insurance. Additionally, the symptoms of depression, such as fatigue and lack of motivation, may preclude treatment-seeking efforts (Cooper-Patrick, et al., 1997). The likelihood of seeking treatment for depression is higher among females, people who are highly educated, and those older in age. Factors related to depression that are also positively associated with help seeking include prior treatment for depression, the length and severity of the depressive episode, and greater impairment associated with depression (Blumenthal and Endicott, 1996; Galbaud du Fort et al., 1999). Once an individual consults a provider about their symptoms or is identified as having depression, he or she must then be willing to accept the diagnosis and adhere to the prescribed treatment regimen (Goldman, et al., 1999). Concerns about treatments, such as side effects of medications or time needed to attend therapy sessions, may hinder adherence (Cooper-Patrick, et al., 1997). People with epilepsy may face additional barriers to being diagnosed and treated for depression. People with active seizures cannot obtain a driver‘s license and, therefore, are reliant on public transportation, family, or friends to make doctor appointments. Moreover, people with epilepsy and depression tend to have less support from others (Hermann and Whitman, 1989; Reisinger and DiIorio, 2009), and thus may have more difficulty getting to appointments. The additional burden of doctor visits can also present a prohibitive cost element, especially since depression among people with epilepsy is associated with being unemployed, having low income, and experiencing financial stress (Ettinger, et al., 2004; Hermann and Whitman, 1989). Some people with epilepsy do not want to add medications to their current regimen or feel that their depressive symptoms may be temporary and do not need treatment (Barry, et al., 2008).
266
Elizabeth Reisinger Walker and Colleen DiIorio
Provider-Level Factors The most important component in the recognition of depression is the patient‘s physician. General practitioners can be a gateway into mental health services, though they often do not detect depression in their patients. Providers may lack knowledge about mental health problems, the skills to identify symptoms, or the time for screening and referral (Collins, et al., 2004; Wiegartz, et al., 1999). Additionally, detection and diagnosis depends on the degree to which the patient‘s symptoms are outwardly presented (Collins, et al., 2004). People with chronic diseases often present with somatic symptoms resulting from their depression that may be difficult to disentangle from their chronic condition (Goldman, et al., 1999). Borowsky and colleagues (2000) found that physicians are less likely to detect depression among African Americans, men, and younger patients, but were more likely to recognize depression in patients with diabetes or hypertension. The authors suggest that care of chronic conditions, which often require frequent trips to the provider, provide an opportunity for physicians to know their patients better and thus recognize mental distress (Borowsky, et al., 2000). Treatment of depression can be hindered by lack of knowledge and skills related to evidence-based treatments among both general physicians and mental health practitioners (Collins, et al., 2004). The patient-provider relationship and an individual‘s satisfaction with their care are important elements related to the quality of mental health care received (Meredith et al., 2001) and continuation of treatment. A person‘s perception of their provider‘s medical and interpersonal skills can affect their willingness to share information about sensitive topics related to depression (Cooper-Patrick, et al., 1997). Several factors influence provider‘s recognition and diagnosis of depression among people with epilepsy. Shneker and colleagues (2009) found that 62% of providers in the United States who treat epilepsy do not screen for depression, and 42% are not comfortable initiating treatment for depression. Discussions of depression and other mood-related topics occur infrequently between patients and neurologists (Gilliam, et al., 2009). Providers treating epilepsy may not have time during the visits with their patients to discuss mental health topics in addition to seizure and medication management or they may feel that their responsibility is to focus on the epilepsy rather than other conditions. Additionally, providers may not screen for or diagnose depression among people with epilepsy because of the misconception that depression comorbidity with a medical disorder does not need to be treated (Barry, 2003). Sometimes depression in people with epilepsy may not be easily classified according to the diagnostic criteria, which could impede recognition of the disorder by both providers and patients (Krishnamoorthy, 2003). Finally, providers may also be wary of prescribing an antidepressant because of potential interactions with antiepileptic drugs, despite recommendations to treat with antidepressants and guidelines for choosing an appropriate medication (Barry et al., 2008).
System-Level Factors System-level factors are also important when considering provision of depression treatment. In the United States, the United Kingdom, and other countries, depression is increasingly being treated in a primary care setting (Haddad, 2009; Kessler, et al., 2005;
Depression in People with Epilepsy
267
Olfson, et al., 2002). The shift in service delivery has been accompanied by increases in the rate of outpatient treatment for depression and use of antidepressants (Olfson, et al., 2002). Despite the increased use of depression treatment, the quality of treatment is not assured (Goldman, et al., 1999) and an unmet need for mental health services persists (Mojtabai, 2009). Several system-level challenges may prevent individuals from receiving needed services. Mental health care is often described as being fragmented, or existing in a system apart from the general health system. This fragmentation is partially due to the historical treatment of mental illnesses in institutional settings (Salize et al., 2007). Separation between the medical and mental health care systems based on geographic location of services, different funding mechanisms, lack of communication and information sharing between providers, and cultural differences hamper quality of care (Druss, 2007). While deinstitutionalization has occurred over the past thirty to fifty years across the globe, and people with mental illnesses are more likely to receive treatment in community settings, variation does exist between countries. In Russia, for example, many people are still treated in hospitals, in large part due to outdated financing systems from the Soviet era (McDaid, et al., 2006). In developing or newly industrial countries, mental health resources, including facilities, trained professionals, and methods for data collection and tracking, are extremely scarce (Larrobla and Botega, 2001; Shinfuku, 1998). Countries are working to overcome these systemic barriers to mental health treatment. For example, in the United States, the passage of the mental health parity law in October 2008 removed a major barrier by requiring insurance companies to provide equal coverage for mental and physical conditions. However, there are limitations to the law. For instance, small companies are not required to comply, and insurance companies can decide which mental disorders to cover (Bernstein, 2008). In other countries, ongoing efforts are being made, such as improving access to community-based treatments in Russia and Japan (McDaid, et al., 2006; Shinfuku, 1998) and passage of Mental Health Laws in Taiwan, Korea, and other Asian countries to protect the human-rights and community-based treatment options for people with mental illnesses (Shinfuku, 1998).
Addressing Barriers to Diagnosis The need for greater recognition and treatment of depression among people with epilepsy has been firmly established in recent conferences and in the literature (Barry, 2003; Barry, et al., 2008; Barry and Jones, 2005; Jones et al., 2005). The Centers for Disease Control and Prevention acknowledged the barriers people with epilepsy face in receiving adequate mental health care during their Living With Epilepsy II Conference in 2003 (American Epilepsy Society, Centers for Disease Control and Prevention, Chronic Disease Directors, Epilepsy Foundation, and National Association of Epilepsy Centers, 2003; Austin, Carr, and Hermann, 2006). One of the recommendations for improving quality of life was to ―Increase the availability of mental health assessments and treatment at comprehensive epilepsy centers and within the public health system‖ (American Epilepsy Society, et al., 2003, p. 24). Additionally, many reviews have been written about treating depression in people with epilepsy (for example: Barry, 2003; Barry and Jones, 2005; Gilliam and Kanner, 2002;
268
Elizabeth Reisinger Walker and Colleen DiIorio
Harden, 2002; Krishnamoorthy, 2003). While the authors discuss prevalence figures, possible etiologies, and treatment recommendations, they do not address barriers or facilitators to recognition and treatment, methods for overcoming barriers, or models for integrated care. Similarly, few investigators have examined ways to address this problem, especially at a system- and policy-level.
Individual-Level Factors People do not seek treatment for depression for a variety of reasons, including not recognizing the symptoms of depression, belief in their own ability to manage the symptoms, or fear of stigma related to the diagnosis of depression. Education of people with epilepsy will help overcome these barriers. Patient education materials on depression are available for distribution by health care organizations. One way to educate patients is to purchase and place these materials in waiting rooms and clinics. Epilepsy websites can provide information about depression and links to depression websites in order to foster learning about the condition. In addition to pharmacologic and counseling approaches to treatment, people can manage symptoms through development of stress management skills. Active involvement in care leads to more effective management of depression, so self-management training and support should be provided to those diagnosed with depression. Other approaches include exercising, positive coping strategies, avoidance of risk behaviors such as drug and alcohol use, and support from family and friends. As programs to treat depression that can be delivered in the home are developed, it will be necessary to make people with epilepsy aware of these alternative treatment methods.
Provider-Level Factors Experts in the field of epilepsy research recommend screening all people with epilepsy for depression, followed by further evaluation and treatment for those who exhibit symptoms of depression (Barry, et al., 2008). Universal screening can potentially address several barriers that prevent the recognition and diagnosis of depression in people with epilepsy. Often, people with depression may not recognize or acknowledge the depressive symptoms they experience or they may be unaware of treatment options. Depression screening gives providers with an opportunity to broach the potentially sensitive topic of depression with their patients. Providers also may be alerted to the presence of depression in patients who do not outwardly seem depressed or may be complaining of mainly somatic symptoms. Several depression screening tools have been validated among people with epilepsy, including common scales such as the Beck Depression Inventory (BDI), the Center for Epidemiological Study of Depression (CES-D) and the Patient Health Questionnaire (PHQ9), and an epilepsy-specific measure, the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E; Friedman, et al., 2009; F. G. Gilliam, et al., 2006; Jones, Hermann, Woodard, et al., 2005; Seminario, Farias, Jorgensen, Bourgeois, and Seyal, 2009). Gilliam and colleagues (2006) developed the NDDI-E to account for the fact that some symptoms of depression, such as fatigue, problems with memory and concentration, appetite change, and sleep disturbances, overlap with possible side-effects of anti-epileptic medication or
Depression in People with Epilepsy
269
symptoms associated with having epilepsy. This short instrument, therefore, assesses the frequency of depressive symptoms that are not similar to those that might result from epilepsy or anti-epileptic medication. The scale includes six items, which are rated on a four-point Likert scale from ―never‖ to ―always or often.‖ Respondents indicate how often over the past two weeks, including the day of assessment, they experienced each of the items: everything is a struggle, nothing I do is right, feel guilty, I would be better off dead, frustrated, difficulty finding pleasure (F. G. Gilliam, et al., 2006). Despite the existence of brief validated measures, the majority of practitioners who treat people with epilepsy do not screen for depression (Shneker, et al., 2009) and only a couple investigators have studied screening procedures. Seminario and colleagues (2009) used the PHQ-9 to determine depression prevalence among people who visited an epilepsy clinic. Almost 30% of the patients screened scored high enough on the PHQ-9 to indicate likely major depression; half of these patients had not received treatment for their depression (Seminario, et al., 2009). In an urban clinic, Friedman and colleagues (2009) implemented a systematic screening procedure with the NDDI-E, followed by a structured interview for individuals who screened positive for depression. Depression was identified in about 25% of the screened sample, compared to 2.6% in a group of patients that was not systematically screened. This finding suggests that screening can be an effective method of identifying people with epilepsy who also suffer from depression (Seminario, et al., 2009). What is not clear from these studies, however, is the process by which the patients with depression are linked up with treatment. More research is needed on how to facilitate this process and identify resources available or needed at clinics. Other approaches for increasing the recognition, diagnosis, and treatment of depression include continued provider education on evidence-based screening and treatment options, strategies to improve patient-provider relationships, and encouraging collaboration between neurologists, epileptologists, and mental health providers. Because many providers who treat epilepsy do not discuss depression with their patients, due to either time constraints or discomfort with the topic (F. Gilliam, et al., 2009; Shneker, et al., 2009), it is important to explore ways, in addition to screening, to improve patient-provider communication about depression. Such methods could include incorporating patient-oriented communication strategies such as motivational interviewing.
System-Level Factors Dealing with depression as a chronic illness requires long-term care and monitoring. The major system-level barrier to effective depression treatment is the fragmentation medical and mental health systems. Collaborative models of care seek to bridge this gap and have demonstrated effectiveness in providing high quality of care for people with depression. In order to be successful, collaborative models require a restructuring of traditional health care delivery systems and participation from actors at all levels of the system. Patients are encouraged to become informed and activated in order to take part in self-management activities. Providers work in multidisciplinary teams to coordinate acute care and chronic disease management. Computerized information systems provide reminders, provider feedback, and patient registries (Bodenheimer, Wagner, and Grumbach, 2002). Additionally, financial systems are put in place to address the separation between funding streams for
270
Elizabeth Reisinger Walker and Colleen DiIorio
medical and mental health and appropriately reimburse providers for services (Kilbourne, et al., 2004; Mauer and Druss, 2009). The multi-level nature of these models and the need to tailor any approach to the realities of individual health care systems presents substantive challenges to their implementation. However, collaborative care models have been successfully employed in numerous settings (Bodenheimer, et al., 2002). One reason for the success is the stepped approach to care in which intensity of care increases based on symptoms (W. J. Katon and Seelig, 2008). Primary care physicians are involved at step 1 and provide screening, diagnosis, treatment, and education. Patients who are newly diagnosed or relapsed move to step 2 care that involves allied health professionals who closely monitor the patient and provide follow-up support. Patients who do not response to initial treatment are referred to a psychiatrist or mental health professional for more accurate diagnosis and more intensive care (step 3). Some of these latter patients with more severe symptoms may progress to step 4 in which the psychiatrist assumes primary responsibility for ongoing management. These patients may need a combination of treatments and close monitoring for longer periods of time. Continued reevaluation of patients is an important component of the stepped care approach; patients can move up or down the steps so that their care matches their changing needs. Collaborative care has been successfully incoporated into primary care settings to treat depression. In a systematic review of educational and organization interventions for depression management, Gilbody and colleagues (2003) found that successful interventions targeted multiple levels with diverse strategies, such as clinician education, nurse case management, and interaction between primary and secondary care. Interventions with simplistic approaches, such as only providing treatment guidelines or clinician education, proved to be ineffective in reducing depressive symptoms among patients. In particular, case management has emerged as an effective component in depression care (Christensen, et al., 2008; Gilbody, et al., 2003). The role of the case manager can include patient assessment, patient and provider education, and monitoring over time (Bruce, et al., 2004; Dietrich, Oxman, Burns, Winchell, and Chin, 2003; Unutzer, et al., 2002). Patients who interact with case managers report significantly greater reductions in depressive symptoms compared to usual care patients (Bruce, et al., 2004; Christensen, et al., 2008; Gilbody, et al., 2003; Unutzer, et al., 2002). Barry (2003) notes that epilepsy clinics may be able to implement treatment paradigms such as psychiatric liaison strategies, nurse educators, and collaborative care models. He notes, ―Collaborative care that includes a fusion of psychiatry and neurology is clearly needed, and people with epilepsy and depressive disorders will benefit greatly from improved treatment‖ (Barry and Jones, 2005, p. 526). Currently, no studies have been reported in the literature on the application of chronic disease management models to treat people with epilepsy, with or without depression. These models theoretically could be used to improve quality of care for both epilepsy and depression.
Depression in People with Epilepsy
271
Treating Depression in Epilepsy Depression Treatments Current recommendations for treating depression in people with epilepsy include antidepressant medications (Gilliam, 2005; Krishnamoorthy, 2003) and cognitive behavioral therapy (CBT). After starting patients with epilepsy on depression treatment, providers must follow-up regularly to assess for side-effects and suicidal ideation (Barry and Jones, 2005).
Pharmaceuticals The first classes of antidepressants, monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs), were introduced in the 1950s. The efficacy of these medications in reducing depressive symptoms has been documented by numerous studies; however they caused unpleasant side effects and had the potential to adversely interact with other drugs. A newer class of antidepressants, selective serotonin re-uptake inhibitors (SSRIs), has also been shown to be effective, with fewer side effects (Cipriani et al., 2007; Judd, 1998). When prescribing antidepressants for people with chronic conditions, providers must take into account possible interactions with other prescription medications and how the sideeffects may affect the chronic condition (Pilling et al., 2009). When treating depression in epilepsy, it is recommended to start a patient on a low dose SSRI and gradually increase the dose to reduce the risk of increasing seizures (Barry, et al., 2008). Continuous medication management and assessment of adherence is important because many people stop taking antidepressants before completing a full therapeutic course (Cassano and Fava, 2002).
Therapy Cognitive behavioral therapy (CBT) developed out of Aaron Beck‘s Cognitive Therapy, which he designed based on his research with depression. Beck recognized that thought patterns affect mood and that how people perceive their experiences can influence their feelings and behaviors (Corey, 2005). CBT is a combination of strategies that can be used to alter automatic thought processes and behaviors. A major component of depression is the negative thought processes. People who are depressed often think discouraging and fatalistic thoughts such as ―I am at fault,‖ ―I can‘t do anything right,‖ or ―I will not be able to succeed no matter what I do.‖ CBT is insight-focused and involves changing how people think about themselves and their reaction to events and situations. They learn how to identify negative thoughts and modify those thoughts into positive or at least neutral thinking and not to accept the negative result as inevitable. To help with the process of learning how to think differently, a person in therapy is generally given behavioral strategies to help. One strategy involves using a diary to record events and thoughts about the events. Information from the diary is then used to help people evaluate situations, recognize patterns in their thinking, and learn to be less critical and more rational about their performance. Using the diary and other strategies are often assigned as homework between sessions to encourage routinization of the thought
272
Elizabeth Reisinger Walker and Colleen DiIorio
identification and modification skills. The skills learned during limited sessions (up to 20) can be used in the future to deal with stressful situations after the treatment ends. Extensive research has been conducted to determine the effectiveness of CBT in reducing depressive symptoms and preventing relapse. Vittengl and colleagues (2007) performed a systematic review and meta-analysis of the effects of CBT on relapse and recurrence of depression. They found that CBT was more effective at preventing relapse and recurrence compared to a course of anti-depressants alone. Continuation of CBT after remission significantly prevented relapse/recurrence of depression compared to medication or treatment discontinuation (Vittengl, et al., 2007). Although the exact mechanisms through which CBT works are not entirely understood, it is thought that changes in underlying beliefs about the self and explanations for negative events, along with acquisition of cognitive coping skills, contribute to the lasting effects of CBT (Barber and DeRubeis, 2001; Hollon et al., 2006). Research among people with epilepsy and depression has shown that cognitive behavioral methods have been effective for reducing depressive symptoms (Davis et al., 1984), reducing the impact of epilepsy-related problems (Goldstein et al., 2003), and increasing overall quality of life and seizure management (Au, et al., 2003). Based on a systematic review, however, Ramaratnam and colleagues (2008), recommend additional research to fully support the claim that cognitive behavioral and other psychological methods for treating depression reduce seizure frequency and lead to improved quality of life. Interpersonal Therapy (IPT) seeks to help the person gain competence with interpersonal skills. Depression is often accompanied by a loss of interest and subsequent withdrawal from social functions, further compounding feelings of worthlessness. Interpersonal therapy is particularly helpful when depression relates to loss or change, creating a situation in which relationships have changed or are strained, for example after the death of a loved one, moving to a new city, changing a job or medical illness. IPT focuses on current problems and helps people find better ways to deal with situations. For example, a person recently diagnosed with epilepsy may face changes in his/her role. The focus would be on what the person is giving up in the old role and taking on in the new role, what emotions surround the change, expressing emotions about the change, and developing skills for the new role. The person may also experience grief; IPT would deal with acceptance of difficult emotions and replacement of lost relationships. IPT is also effective in reducing depression; its efficacy appears to be similar to that of antidepressants and CBT (de Mello et al., 2005; Hollon, et al., 2006). Additionally, IPT enhances the quality of relationships (Hollon, et al., 2006). The proposed mechanism of IPT is that changes and improvements in relationships reduce interpersonal difficulties that may trigger or worsen negative mood (Kelly et al., 2007). Currently, research is lacking on the effect of IPT on treating depression in people with epilepsy; however IPT methods appear to be appropriate for addressing the needs of people with epilepsy and depression.
Mindfulness Mindfulness practices developed as part of the Buddhist tradition over 2500 years ago. Only more recently has mindfulness received attention within Western psychology and been incorporated into treatments for depression. Despite the different origins of mindfulness and psychotherapy, both practices strive to alleviate psychological suffering and propose a plan
Depression in People with Epilepsy
273
for doing so (Germer, 2005; Rubin, 1999). Mindfulness is fully compatible with various theories of psychotherapy and has the potential to provide benefits to both the therapist and the patient. Mindfulness has been defined variously as ―…paying attention in a particular way: on purpose, in the present moment, and nonjudgmentally‖ (Kabat-Zinn, 1994, p. 4) and ―awareness of present experience with acceptance‖ (Germer, 2005, p. 7). It is a process of observing what is going on moment-to-moment, which moves the practitioner away from automatic patterns of thinking, especially those concerned with the past or future. Mindfulness teaches people to develop a different relationship with their thoughts, one that is more ‗detached‘ and less reactive (Segal et al., 2002). Mindfulness can take on a variety of forms including formal sitting meditation and exercises designed to foster mindful awareness of breath, body, sensations, thoughts, or actions (Kabat-Zinn, 1990; Mace, 2007; Segal, et al., 2002). As suggested by Martin (1997), ―…mindfulness would appear to help facilitate an optimal circumstance for psychological change‖ (Martin, 1997, p. 292). Segal et al. (2002) fused mindfulness and CBT in their Mindfulness-Based Cognitive Therapy (MBCT), an eight week depression treatment program for small groups. According to MBCT, vulnerability to relapse and recurrence of depression is linked to repeated associations between depressed mood and negative patterns of thinking, which lead to altered thinking patterns and physiological responses. Teaching people how to identify negative thoughts and feelings and then respond mindfully by disengaging from those thoughts, and thus prevent ruminative cycles of thinking, should aid in preventing the spiral into serious depression (Segal, et al., 2002). Studies on MBCT have shown that it is effective in preventing relapse among people who have experienced three or more episodes of depression (Ma and Teasdale, 2004; Teasdale, et al., 2000). Participants in MBCT programs have noted that the program fostered greater awareness and acceptance of events, relaxation, and better coping. They also appreciate the group support aspect of the program and often report practicing mindfulness skills after the program ends (Mason and Hargreaves, 2001;Smith et al., 2007). The incorporation of mindfulness-based techniques for treatment of depression among people with epilepsy is described below in the Project UPLIFT study.
Motivational Interviewing Motivational Interviewing (MI) is a communication style developed by Miller and Rollnick (2002) to encourage individuals to take responsibility for their behavior and for their decisions and actions to modify behaviors. The aim of MI is for the facilitator to work with the individual, creating a collaborative bond, and encourage him or her to find internal motivation for change. MI was originally developed to address problem drinking behaviors (L. Miller and Rollnick, 2002; W. Miller, 1995), but has since been applied to a variety of conditions and behaviors including mental disorders (Lundahl and Burke, 2009), smoking cessation (Colby, et al., 1998), fruit and vegetable intake (Resnicow, et al., 2001), and adherence (DiIorio, et al., 2003; Smith et al., 1997). Rubak and colleagues (2005) conducted a systematic review and meta-analysis of interventions using MI and found that MI significantly improved behavior change and health outcomes. The goal of the MI counselor is to create a nonjudgmental and supportive environment that will allow the person to take an active part in the session and openly discuss positive and
274
Elizabeth Reisinger Walker and Colleen DiIorio
negative thoughts and feelings related to behavior change. An MI counseling session often begins with an assessment of the person‘s behavior and his or her motivation, confidence, and readiness to change or maintain a desired behavior. One objective is to uncover barriers to behavioral performance through the use of open-ended questions, reflective listening (i.e., paraphrasing key statements and presenting interpretive comments), reinforcement of change talk (statements that indicate willingness to change behavior), and provision of affirmations (supportive comments). The MI counselor also uses techniques to address discrepancies and ambivalence to change. Toward the end of the session, the person creates an action plan that includes specific performance goals (L. Miller and Rollnick, 2002). Combining MI with psychotherapy provides an opportunity for enhanced patient engagement in their treatment (Lundahl and Burke, 2009). Although MI techniques have not yet been used to address depression among people with epilepsy, a program aimed at improving self-management behaviors that incorporated MI was shown to improve self-management and self-efficacy (DiIorio et al., 2009).
Innovative Approaches to Treating Depression among People with Epilepsy Innovative approaches for treating depression among people with epilepsy could potentially reduce the burden of depression in this population. As noted above, brief screening measures can aid physicians and neurologists in screening for depression among people with epilepsy (Friedman, et al., 2009; Seminario, et al., 2009). Screening and identification of people with depression can hopefully facilitate treatment through antidepressants and therapy. An alternative, and complementary, procedure for treating people with depression could include interventions based on cognitive behavioral or other psychotherapeutic methods delivered to the person with epilepsy at their home, rather than at a physician‘s or therapist‘s office. These interventions could be offered over the internet or telephone, or involve home visits. The benefits of providing treatment for depression through distance delivery include improved access, especially among a population that may experience mobility difficulties, and potential cost-effectiveness because the programs can be delivered by non-professionals and sometimes in a group setting. Interventions also have the potential to address determinants of depression, for example, lack of social support, which are more difficult to alter though physician visits. This section provides a short review of innovative interventions for treating depression among people with epilepsy, many of which employ strategies and treatments discussed above.
In Person -- Clinic and Home Currently, Ciechenowski and colleagues are adapting an intervention originally developed for socially isolated older adults for people with epilepsy (Ciechanowski, et al., 2004; Managing Epilepsy Well, 2010b). The initial program, titled Program to Encourage Active, Rewarding Lives for Seniors (PEARLS), involved trained therapists visiting participants in their home to deliver eight 50-minute sessions over the course of 19 weeks.
Depression in People with Epilepsy
275
The sessions are based on problem-solving treatment, which focuses on skill building, identifying daily problems that affect mood, and addressing these problems in order to ultimately reduce depressive symptoms. The sessions emphasize social and physical activities and encourage participants to select pleasant activities to engage in between sessions. A random controlled trial of the PEARLS program was conducted among older adults with minor depression or dysthymia. Participants in the programs had a significant decrease in depressive symptoms, greater remission, and improvement in functional and emotional wellbeing when compared to the usual-care control group (Ciechanowski, et al., 2004). The modified intervention will target people with epilepsy and major depression, minor depression, and dysthymia (Managing Epilepsy Well, 2010b).
Distance Delivery - Telephone and Internet Although few interventions for people with epilepsy have utilized distance delivery methods, the literature contains several examples of CBT-based programs for general populations. The effects of internet and phone-based interventions include improvement in depression scores, lower severity of symptoms, greater remission rates, and improved functioning (Andersson, 2006; W. Katon and Ciechanowski, 2002; D. Kessler, et al., 2009). These programs usually include multiple weekly sessions, often led by a therapist or trained facilitator. Clarke and colleagues (2005; 2002) developed ODIN (Overcoming Depression on the InterNet), a self-help program that included CBT-based cognitive restructuring principles. A trial of ODIN that included both the internet program and telephone reminders resulted in improvement in depression scores for both moderately and severely depressed participants (Clarke, et al., 2005). Participants in other internet-based programs, including Beating the Blues (Proudfoot, et al., 2004) and MoodGYM (Christensen, Griffiths, and Jorm, 2004), reported significantly lowered depression scores compared to either a control group or a group who accessed an informational web-site on depression, respectively. Telephone-based programs demonstrate similar efficacy. Mohr and colleagues (Mohr, et al., 2005; 2000) tested a 16-week telephone CBT program for people with multiple sclerosis and reported improvements in positive affect and some depression measures. Finally, telephone care management for depression accompanied by telephone psychotherapy resulted in significant reductions in depressive symptoms, while only marginally increasing health services costs compared to regular care (Simon et al., 2009). In addition to effectively treating depression, participants rate internet- and telephonebased programs highly in regards to satisfaction. In one study, participants‘ reported satisfaction and preference was comparable whether they participated in the computer program or interacted with a therapist face-to-face (Gega et al., 2004). The participants in Beating the Blues also reported being satisfied with CBT over the computer (Proudfoot, et al., 2004). Wright et al. (2005) showed that patients expressed high levels of satisfaction with their computer-assisted therapy program, which was user-friendly, interactive, and designed to be used by people with low computer literacy. One intervention aimed at reducing depressive symptoms among people with epilepsy through distance delivery methods has been tested. Project UPLIFT (Using Practice and Learning to Increase Favorable Thoughts) is a CBT and mindfulness-based program that is designed to be delivered in groups over the phone or internet (Thompson, et al., Under
276
Elizabeth Reisinger Walker and Colleen DiIorio
review). The Project UPLIFT intervention includes 8 weekly sessions that focus on developing cognitive behavioral and mindfulness skills. The intervention was efficacious in reducing depressive symptoms and increasing knowledge and skills related to CBT and mindfulness compared to the control group (Thompson, et al., Under review). Participants in the pilot study of Project UPLIFT also expressed satisfaction with the program, perceived the intervention to be beneficial, and enjoyed interacting with group members (Reisinger Walker, Obolensky, Dini, and Thompson, Under review). The results of other studies indicate that distance delivery is a feasible and acceptable method for disseminating interventions to people with epilepsy. Escoffery and colleagues (2007) conducted a survey over the internet and at two epilepsy clinics. They found that 99% of the internet respondents and 57% of clinic participants used the internet to find health information. A majority of the respondents reported being likely to use an internet-based selfmanagement program (Escoffery, et al., 2007). One such program is WebEASE (Epilepsy Awareness, Support, and Education), an online theory-based self-management program aimed at improving medication adherence, enhancing sleep quality, and reducing stress. Participants in the pilot study showed some improvements in epilepsy self-management, sleep quality, epilepsy self-efficacy and social support (DiIorio et al., 2009). A larger randomized control trial is currently underway to test the efficacy of the program (Managing Epilepsy Well, 2010a). DiIorio and colleagues (2009) have also pilot tested a telephone self-management program; participants were satisfied with the program and showed modest improvements in self-efficacy, outcome expectancies related to medication and managing seizures, and knowledge of the social aspects of epilepsy. Either program could be easily adapted to address depressive symptoms.
Summary Depression is a major public health problem and presents a great burden for people with chronic diseases, including individuals with epilepsy. The biological consequences and stressors from having a chronic disease can increase an individual‘s risk for having a depressive episode. Additional psychosocial variables can reduce coping abilities and increase the likelihood for a person to develop depression. For example, predictors of depression among people with epilepsy include unemployment, financial strain, stigma, and low social support. Depression negatively affects quality of life, functioning, and relationships, thus causing further stress. People with epilepsy face a variety of person, provider, and systematic barriers for being diagnosed with and treated for depression. At the patient level, an individual‘s decision to seek treatment may be hampered by acceptance of their symptoms, fear of stigma, willingness to discuss their condition with a provider, and accessibility of treatment. Barriers at the provider level include a lack of time or, possibly, inclination to discuss depression with patients. Providers also may not have the knowledge or skills to diagnose and adequately treat depression. At a systems level, the lack of integration of mental health and general medical services can preclude the availability of affordable and quality care for depression. Developing countries face additional challenges in being able to provide community-based treatment.
Depression in People with Epilepsy
277
Despite the negative impact of depression and the barriers to recognition and treatment, depression can be successfully treated once identified. The stigma of depression is on a downward trend as people become more educated about the condition and treatment options. Primary care doctors or specialists can serve as a gateway to mental health services by providing medication and referring for therapy. Using brief screening measures, such as the PHQ-9 and NDDI-E, are one way to improve the recognition of depression among people with epilepsy. Additionally, researchers are currently developing and testing innovative interventions to combat depression and promote self-management behaviors. Such interventions can be delivered to the individuals‘ homes through in-person visits or distance technology. Also, these programs do not necessarily need to be administered by providers or mental health professionals. For example, Project UPLIFT employs people with epilepsy to facilitate the intervention groups. A psychologist oversees the project, but reaches many more people than she would if delivering therapy face-to-face. This type of set up may ultimately help to relieve burden on the providers and represent a cost-savings. Finally, at a systemslevel, progress is being made to improve access to treatment, financing systems, and data collecting procedures. Continuing efforts need to be made to address the risk factors for depression and the barriers to diagnosis and treatment among people with epilepsy, at all levels. Future research should continue explore the factors that predict depression and how to best address them in order to prevent depression. Additionally, it will be important to investigate how to integrate depression screening protocols and collaborative care models into primary care and neurology practices to facilitate the detection of depression and initiation of treatment. As the results of intervention trials, such as PEARLS and Project UPLIFT, are published, the next step will be to determine how to most effectively use the programs in real-world settings. Finally, policy reform to remove systematic barriers to receiving treatment will ultimately benefit all people with depression.
References American Epilepsy Society, Centers for Disease Control and Prevention, Chronic Disease Directors, Epilepsy Foundation, and National Association of Epilepsy Centers. (2003). Living well with epilepsy II: Report of the 2003 national conference on public health and epilepsy - priorities for a phublic health agenda on epilepsy. from http://www.cdc.gov/ Epilepsy/pdfs/living_well_2003.pdf American Psychiatric Association. (2000). Diagnositc and statistical manual of mental disorders (Vol. 4th ed., text revision). Washington, DC: American Psychiatric Association. Andersson, G. (2006). Internet-based cognitive-behavioral self help for depression. Expert Rev. Neurother, 6(11), 1637-1642. Au, A., Chan, F., Li, K., Leung, P., Li, P., and Chan, J. (2003). Cognitive-behavioral group treatment program for adults with epilepsy in Hong Kong. Epilepsy Behav, 4(4), 441-446. Austin, J. K., Carr, D. A., and Hermann, B. P. (2006). Living Well II: a review of progress since 2003. Epilepsy Behav, 9(3), 386-393.
278
Elizabeth Reisinger Walker and Colleen DiIorio
Baker, G. A., Brooks, J., Buck, D., and Jacoby, A. (1999). The stigma of epilepsy: A european perspective. Epilepsia, 41(1), 98-104. Baker, G. A., Jacoby, A., Buck, D., Stalgis, C., and Monnet, D. (1997). Quality of life of people with epilepsy: a European study. Epilepsia, 38(3), 353-362. Barber, J. P., and DeRubeis, R. J. (2001). Change in Compensatory Skills in Cognitive Therapy for Depression. The Journal of Psychotherapy Practice and Research 10, 8-13. Barry, J. J. (2003). The recognition and management of mood disorders as a comorbidity of epilepsy. Epilepsia, 44 Suppl 4, 30-40. Barry, J. J., Ettinger, A. B., Friel, P., Gilliam, F. G., Harden, C. L., Hermann, B., et al. (2008). Consensus statement: the evaluation and treatment of people with epilepsy and affective disorders. Epilepsy Behav, 13 Suppl 1, S1-29. Barry, J. J., and Jones, J. E. (2005). What is effective treatment of depression in people with epilepsy? Epilepsy Behav, 6(4), 520-528. Barth, J., Schumacher, M., and Herrmann-Lingen, C. (2004). Depression as a risk factor for mortality in patients with coronary heart disease: a meta-analysis. Psychosom. Med, 66(6), 802-813. Baune, B. T., Adrian, I., and Jacobi, F. (2007). Medical disorders affect health outcome and general functioning depending on comorbid major depression in the general population. J. Psychosom. Res, 62(2), 109-118. Beran, R. G. (1999). The burden of epilepsy for the patient: the intangible costs. Epilepsia, 40 Suppl 8, 40-43. Bernstein, E. (2008, October 16). How new law boosts coverage of mental care. The Wall Street Journal. Bishop, M. (2002). Barriers to employment among people with epilepsy: Report of a focus group. Journal of Vocational Rehabilitation, 17, 281-286. Blumenthal, R., and Endicott, J. (1996). Barriers to seeking treatment for major depression. Depress Anxiety, 4(6), 273-278. Bodenheimer, T., Wagner, E. H., and Grumbach, K. (2002). Improving primary care for patients with chronic illness. JAMA, 288(14), 1775-1779. Borowsky, S. J., Rubenstein, L. V., Meredith, L. S., Camp, P., Jackson-Triche, M., and Wells, K. B. (2000). Who is at risk of nondetection of mental health problems in primary care? J. Gen. Intern. Med, 15(6), 381-388. Boylan, L. S., Flint, L. A., Labovitz, D. L., Jackson, S. C., Starner, K., and Devinsky, O. (2004). Depression but not seizure frequency predicts quality of life in treatment-resistant epilepsy. Neurology, 62(2), 258-261. Bruce, M. L., Ten Have, T. R., Reynolds, C. F., Katz, I. I., Schulberg, H. C., Mulsant, B. H., et al. (2004). Reducing suicidal ideation and depressive symptoms in depressed older primary care patients: A randomized controlled trial. JAMA, 291(9), 1081-1091. Burneo, J. G., Tellez-Zenteno, J., and Wiebe, S. (2005). Understanding the burden of epilepsy in Latin America: a systematic review of its prevalence and incidence. Epilepsy Res, 66(1-3), 63-74. Canuet, L., Ishii, R., Iwase, M., Ikezawa, K., Kurimoto, R., Azechi, M., et al. (2009). Factors associated with impaired quality of life in younger and older adults with epilepsy. Epilepsy Res, 83(1), 58-65. Cassano, P., and Fava, M. (2002). Depression and public health: an overview. J. Psychosom. Res, 53(4), 849-857.
Depression in People with Epilepsy
279
Centers for Disease Control and Prevention. (2005). Prevalence of epilepsy and health-related quality of life and disability among adults with epilepsy--South Carolina, 2003 and 2004. Morb. Mortal Wkly Rep, 54(42), 1080-1082. Centers for Disease Control and Prevention. (2007). Targeting epilepsy: One of the nation's most common disabling neurological disorders. Retrieved 6/8/2007, from http://www.cdc.gov/nccdphp/publications/AAG/epilepsy.htm Chaplin, J. E., Wester, A., and Tomson, T. (1998). Factors associated with the employment problems of people with established epilepsy. Seizure, 7(4), 299-303. Christensen, H., Griffiths, K. M., Gulliver, A., Clack, D., Kljakovic, M., and Wells, L. (2008). Models in the delivery of depression care: a systematic review of randomised and controlled intervention trials. BMC Fam. Pract, 9, 25. Christensen, H., Griffiths, K. M., and Jorm, A. F. (2004). Delivering interventions for depression by using the internet: randomised controlled trial. BMJ, 328(7434), 265. Ciechanowski, P., Wagner, E., Schmaling, K., Schwartz, S., Williams, B., Diehr, P., et al. (2004). Community-integrated home-based depression treatment in older adults: a randomized controlled trial. Jama, 291(13), 1569-1577. Cipriani, A., Geddes, J. R., Furukawa, T. A., and Barbui, C. (2007). Metareview on shortterm effectiveness and safety of antidepressants for depression: an evidence-based approach to inform clinical practice. Can. J. Psychiatry, 52(9), 553-562. Clarke, G., Eubanks, D., Reid, E., Kelleher, C., O'Connor, E., DeBar, L. L., et al. (2005). Overcoming Depression on the Internet (ODIN) (2): a randomized trial of a self-help depression skills program with reminders. J. Med. Internet Res, 7(2), e16. Clarke, G., Reid, E., Eubanks, D., O'Connor, E., DeBar, L. L., Kelleher, C., et al. (2002). Overcoming depression on the Internet (ODIN): a randomized controlled trial of an Internet depression skills intervention program. J. Med. Internet Res, 4(3), E14. Colby, S. M., Monti, P. M., Barnett, N. P., Rohsenow, D. J., Weissman, K., Spirito, A., et al. (1998). Brief motivational interviewing in a hospital setting for adolescent smoking: A preliminary study. Journal of Consulting and Clinical Psychology, 66(3), 574-578. Collings, J. A., and Chappell, B. (1994). Correlates of employment history and employability in a British epilepsy sample. Seizure, 3(4), 255-262. Collins, K. A., Westra, H. A., Dozois, D. J., and Burns, D. D. (2004). Gaps in accessing treatment for anxiety and depression: challenges for the delivery of care. Clin. Psychol. Rev, 24(5), 583-616. Cooper-Patrick, L., Powe, N. R., Jenckes, M. W., Gonzales, J. J., Levine, D. M., and Ford, D. E. (1997). Identification of patient attitudes and preferences regarding treatment of depression. J. Gen. Intern. Med, 12(7), 431-438. Corcoran, R., and Thompson, P. (1993). Epilepsy and poor memory: who complains and what do they mean? Br. J. Clin. Psychol, 32 ( Pt 2), 199-208. Corey, G. (2005). Theory and practice of counseling and psychotherapy (7th ed.). Belmont: Brooks/Cole - Thompson Learning. Corrigan, P. W., Kerr, A., and Knudsen, L. (2005). The stigma of mental illness: Explanatory models and methods for change. Applied and Preventive Psychology, 11, 179-190. Cramer, J. A., Blum, D., Reed, M., and Fanning, K. (2003a). The influence of comorbid depression on quality of life for people with epilepsy. Epilepsy Behav, 4(5), 515-521. Cramer, J. A., Blum, D., Reed, M., and Fanning, K. (2003b). The influence of comorbid depression on seizure severity. Epilepsia, 44(12), 1578-1584.
280
Elizabeth Reisinger Walker and Colleen DiIorio
Cuijpers, P., and Smit, F. (2002). Excess mortality in depression: a meta-analysis of community studies. J. Affect Disord, 72(3), 227-236. Davis, G. R., Armstrong, H. E., Jr., Donovan, D. M., and Temkin, N. R. (1984). Cognitivebehavioral treatment of depressed affect among epileptics: preliminary findings. J. Clin. Psychol, 40(4), 930-935. de Mello, M. F., de Jesus Mari, J., Bacaltchuk, J., Verdeli, H., and Neugebauer, R. (2005). A systematic review of research findings on the efficacy of interpersonal therapy for depressive disorders. Eur. Arch. Psychiatry Clin. Neurosci, 255(2), 75-82. Dietrich, A. J., Oxman, T. E., Burns, M. R., Winchell, C. W., and Chin, T. (2003). Application of a depression management office system in community practice: a demonstration. J. Am. Board Fam. Pract, 16(2), 107-114. DiIorio, C., Escoffery, C., McCarty, F., Yeager, K. A., Henry, T. R., Koganti, A., et al. (2009). Evaluation of WebEase: an epilepsy self-management Web site. Health Educ. Res, 24(2), 185-197. DiIorio, C., Reisinger, E. L., Yeager, K. A., and McCarty, F. (2009). A telephone-based selfmanagement program for people with epilepsy. Epilepsy Behav, 14(1), 232-236. DiIorio, C., Resnicow, K., McDonnell, M., Soet, J., McCarty, F., and Yeager, K. (2003). Using motivational interviewing to promote adherence to antiretroviral medications: A pilot study. Journal of the Association of Nurses in AIDS Care, 14(2), 52-62. DiIorio, C., Shafer, P. O., Letz, R., Henry, T. R., Schomer, D. L., and Yeager, K. (2006). Behavioral, social, and affective factors associated with self-efficacy for selfmanagement among people with epilepsy. Epilepsy Behav, 9(1), 158-163. Diop, A. G., de Boer, H. M., Mandlhate, C., Prilipko, L., and Meinardi, H. (2003). The global campaign against epilepsy in Africa. Acta Trop, 87(1), 149-159. Donohue, J. M., and Pincus, H. A. (2007). Reducing the societal burden of depression: a review of economic costs, quality of care and effects of treatment. Pharmacoeconomics, 25(1), 7-24. Druss, B. G. (2007). Improving medical care for persons with serious mental illness: challenges and solutions. J. Clin. Psychiatry, 68 Suppl 4, 40-44. Druss, B. G., Rosenheck, R. A., and Sledge, W. H. (2000). Health and disability costs of depressive illness in a major U.S. corporation. Am. J. Psychiatry, 157(8), 1274-1278. Eaton, W. W., Armenian, H., Gallo, J., Pratt, L., and Ford, D. E. (1996). Depression and risk for onset of type II diabetes. A prospective population-based study. Diabetes Care, 19(10), 1097-1102. Egede, L. E. (2007). Major depression in individuals with chronic medical disorders: prevalence, correlates and association with health resource utilization, lost productivity and functional disability. Gen. Hosp. Psychiatry, 29(5), 409-416. Escoffery, C., DiIorio C, Yeager K, McCarty F, Robinson E, Reisinger E, et al. (2007). Epilepsy patients' use of computers and the internet for health information. Epilepsy Behav, in press. Ettinger, A., Reed, M., and Cramer, J. (2004). Depression and comorbidity in communitybased patients with epilepsy or asthma. Neurology, 63(6), 1008-1014. Fincham, F. D., Beach, S. R. H., Harold, G. T., and Osbourne, L. N. (1997). Marital satisfaction and depression: Different causal relationships for men and women? Psychological Science, 8(5), 351-357.
Depression in People with Epilepsy
281
Fisher, R. S., Vickrey, B. G., Gibson, P., Hermann, B., Penovich, P., Scherer, A., et al. (2000a). The impact of epilepsy from the patient's perspective I. Descriptions and subjective perceptions. Epilepsy Res, 41(1), 39-51. Fisher, R. S., Vickrey, B. G., Gibson, P., Hermann, B., Penovich, P., Scherer, A., et al. (2000b). The impact of epilepsy from the patient's perspective II: views about therapy and health care. Epilepsy Res, 41(1), 53-61. Friedman, D. E., Kung, D. H., Laowattana, S., Kass, J. S., Hrachovy, R. A., and Levin, H. S. (2009). Identifying depression in epilepsy in a busy clinical setting is enhanced with systematic screening. Seizure, 18(6), 429-433. Galbaud du Fort, G., Newman, S. C., Boothroyd, L. J., and Bland, R. C. (1999). Treatment seeking for depression: role of depressive symptoms and comorbid psychiatric diagnoses. J. Affect Disord, 52(1-3), 31-40. Gega, L., Marks, I., and Mataix-Cols, D. (2004). Computer-aided CBT self-help for anxiety and depressive disorders: experience of a London clinic and future directions. J. Clin. Psychol, 60(2), 147-157. Germer, C. K. (2005). Mindfulnes: What is it? What does it matter? In C. K. Germer, R. D. Siegel and P. R. Fulton (Eds.), Mindfulness and psychotherapy. New York: The Guilford Press. Gilbody, S., Whitty, P., Grimshaw, J., and Thomas, R. (2003). Educational and organizational interventions to improve the management of depression in primary care: a systematic review. JAMA, 289(23), 3145-3151. Gilliam, F., and Kanner, A. M. (2002). Treatment of depressive disorders in epilepsy patients. Epilepsy Behav, 3(5S), 2-9. Gilliam, F., Penovich, P. E., Eagan, C. A., Stern, J. M., Labiner, D. M., Onofrey, M., et al. (2009). Conversations between community-based neurologists and patients with epilepsy: Results of an observational linguistic study. Epilepsy and Behavior. Gilliam, F. G. (2005). Diagnosis and treatment of mood disorders in persons with epilepsy. Curr. Opin. Neurol, 18(2), 129-133. Gilliam, F. G., Barry, J. J., Hermann, B. P., Meador, K. J., Vahle, V., and Kanner, A. M. (2006). Rapid detection of major depression in epilepsy: a multicentre study. Lancet Neurol, 5(5), 399-405. Goldman, L. S., Nielsen, N. H., and Champion, H. C. (1999). Awareness, diagnosis, and treatment of depression. J. Gen. Intern. Med, 14(9), 569-580. Goldstein, L. H., McAlpine, M., Deale, A., Toone, B. K., and Mellers, J. D. (2003). Cognitive behaviour therapy with adults with intractable epilepsy and psychiatric co-morbidity: preliminary observations on changes in psychological state and seizure frequency. Behav. Res. Ther, 41(4), 447-460. Grabowska-Grzyb, A., Jedrzejczak, J., Naganska, E., and Fiszer, U. (2006). Risk factors for depression in patients with epilepsy. Epilepsy Behav, 8(2), 411-417. Haddad, M. (2009). Depression in adults with a chronic physical health problem: treatment and management. Int. J. Nurs Stud, 46(11), 1411-1414. Harden, C. L. (2002). The co-morbidity of depression and epilepsy: epidemiology, etiology, and treatment. Neurology, 59(6 Suppl 4), S48-55. Hasin, D. S., Goodwin, R. D., Stinson, F. S., and Grant, B. F. (2005). Epidemiology of major depressive disorder: results from the National Epidemiologic Survey on Alcoholism and Related Conditions. Arch. Gen. Psychiatry, 62(10), 1097-1106.
282
Elizabeth Reisinger Walker and Colleen DiIorio
Hermann, B. P., Seidenberg, M., and Bell, B. (2000). Psychiatric comorbidity in chronic epilepsy: identification, consequences, and treatment of major depression. Epilepsia, 41 Suppl 2, S31-41. Hermann, B. P., and Whitman, S. (1989). Psychosocial predictors of interictal depression. Journal of Epilepsy, 2(4), 231-237. Hollon, S. D., Stewart, M. O., and Strunk, D. (2006). Enduring effects for cognitive behavior therapy in the treatment of depression and anxiety. Annu. Rev. Psychol, 57, 285-315. Jacoby, A., Baker, G. A., Steen, N., Potts, P., and Chadwick, D. W. (1996). The clinical course of epilepsy and its psychosocial correlates: findings from a U.K. Community study. Epilepsia, 37(2), 148-161. Jacoby, A., Gorry, J., Gamble, C., and Baker, G. A. (2004). Public knowledge, private grief: a study of public attitudes to epilepsy in the United Kingdom and implications for stigma. Epilepsia, 45(11), 1405-1415. Jacoby, A., Snape, D., and Baker, G. A. (2005). Epilepsy and social identity: the stigma of a chronic neurological disorder. Lancet Neurol, 4(3), 171-178. Jerant, A. F., von Friederichs-Fitzwater, M. M., and Moore, M. (2005). Patients' perceived barriers to active self-management of chronic conditions. Patient Educ. Couns, 57(3), 300-307. Johnson, E. K., Jones, J. E., Seidenberg, M., and Hermann, B. P. (2004). The relative impact of anxiety, depression, and clinical seizure features on health-related quality of life in epilepsy. Epilepsia, 45(5), 544-550. Jones, J. E., Hermann, B. P., Barry, J. J., Gilliam, F., Kanner, A. M., and Meador, K. J. (2005). Clinical assessment of Axis I psychiatric morbidity in chronic epilepsy: a multicenter investigation. J. Neuropsychiatry Clin. Neurosci, 17(2), 172-179. Jones, J. E., Hermann, B. P., Barry, J. J., Gilliam, F. G., Kanner, A. M., and Meador, K. J. (2003). Rates and risk factors for suicide, suicidal ideation, and suicide attempts in chronic epilepsy. Epilepsy Behav, 4 Suppl 3, S31-38. Jones, J. E., Hermann, B. P., Woodard, J. L., Barry, J. J., Gilliam, F., Kanner, A. M., et al. (2005). Screening for major depression in epilepsy with common self-report depression inventories. Epilepsia, 46(5), 731-735. Judd, L. L. (1998). A decade of antidepressant development: the SSRIs and beyond. J. Affect Disord, 51(3), 211-213. Kabat-Zinn, J. (1990). Full catastrophe living: Using the wisdom of your body and mind to face stress, pain and illness. New York: Delacorte. Kabat-Zinn, J. (1994). Wherever you go there you are: Mindfulness meditation in everyday life. New York: Hyperion. Kanner, A. M. (2003). Depression in epilepsy: a frequently neglected multifaceted disorder. Epilepsy Behav, 4 Suppl 4, 11-19. Kanner, A. M. (2008). Depression in epilepsy: a complex relation with unexpected consequences. Curr. Opin. Neurol, 21(2), 190-194. Katon, W., and Ciechanowski, P. (2002). Impact of major depression on chronic medical illness. J. Psychosom. Res, 53(4), 859-863. Katon, W., Lin, E. H., and Kroenke, K. (2007). The association of depression and anxiety with medical symptom burden in patients with chronic medical illness. Gen. Hosp. Psychiatry, 29(2), 147-155.
Depression in People with Epilepsy
283
Katon, W. J. (2003). Clinical and health services relationships between major depression, depressive symptoms, and general medical illness. Biol. Psychiatry, 54(3), 216-226. Katon, W. J., and Seelig, M. (2008). Population-based care of depression: team care approaches to improving outcomes. J. Occup. Environ. Med, 50(4), 459-467. Kelly, M. A., Cyranowski, J. M., and Frank, E. (2007). Sudden gains in interpersonal psychotherapy for depression. Behav. Res. Ther, 45(11), 2563-2572. Kessler, D., Lewis, G., Kaur, S., Wiles, N., King, M., Weich, S., et al. (2009). Therapistdelivered Internet psychotherapy for depression in primary care: a randomised controlled trial. Lancet, 374(9690), 628-634. Kessler, R. C., Demler, O., Frank, R. G., Olfson, M., Pincus, H. A., Walters, E. E., et al. (2005). Prevalence and treatment of mental disorders, 1990 to 2003. N. Engl. J. Med, 352(24), 2515-2523. Kilbourne, A. M., Schulberg, H. C., Post, E. P., Rollman, B. L., Belnap, B. H., and Pincus, H. A. (2004). Translating evidence-based depression management services to communitybased primary care practices. Milbank Q, 82(4), 631-659. Kimiskidis, V. K., Triantafyllou, N. I., Kararizou, E., Gatzonis, S. S., Fountoulakis, K. N., Siatouni, A., et al. (2007). Depression and anxiety in epilepsy: the association with demographic and seizure-related variables. Ann. Gen. Psychiatry, 6, 28. Kleinman, A. (2004). Culture and depression. N. Engl. J. Med, 351(10), 951-953. Kobau, R., DiIorio, C. A., Price, P. H., Thurman, D. J., Martin, L. M., Ridings, D. L., et al. (2004). Prevalence of epilepsy and health status of adults with epilepsy in Georgia and Tennessee: Behavioral Risk Factor Surveillance System, 2002. Epilepsy Behav, 5(3), 358-366. Krauss, G. L., Ampaw, L., and Krumholz, A. (2001). Individual state driving restrictions for people with epilepsy in the US. Neurology, 57(10), 1780-1785. Krishnamoorthy, E. S. (2003). Treatment of depression in patients with epilepsy: problems, pitfalls, and some solutions. Epilepsy Behav, 4 Suppl 3, S46-54. Langlieb, A. M., and DePaulo, J. R., Jr. (2008). Etiology of depression and implications on work environment. J. Occup. Environ. Med, 50(4), 391-395. Larrobla, C., and Botega, N. J. (2001). Restructuring mental health: a South American survey. Soc. Psychiatry Psychiatr Epidemiol, 36(5), 256-259. Lehti, A., Hammarstrom, A., and Mattsson, B. (2009). Recognition of depression in people of different cultures: a qualitative study. BMC Fam. Pract, 10, 53. Lerner, D., and Henke, R. M. (2008). What does research tell us about depression, job performance, and work productivity? J. Occup. Environ. Med, 50(4), 401-410. Loring, D. W., Meador, K. J., and Lee, G. P. (2004). Determinants of quality of life in epilepsy. Epilepsy Behav, 5(6), 976-980. Lundahl, B., and Burke, B. L. (2009). The effectiveness and applicability of motivational interviewing: a practice-friendly review of four meta-analyses. J. Clin. Psychol, 65(11), 1232-1245. Ma, S. H., and Teasdale, J. D. (2004). Mindfulness-based cognitive therapy for depression: replication and exploration of differential relapse prevention effects. J. Consult. Clin. Psychol, 72(1), 31-40. Mace, C. (2007). Mindfulness in psychotherapy: An introduction. Advances in Psychiatric Treatment, 13, 147-154.
284
Elizabeth Reisinger Walker and Colleen DiIorio
Managing Epilepsy Well. (2010a). Evaluating the effectiveness of epilepsy self-management programs: WebEase (Epilepsy Awareness, Support and Education). Retrieved January 12, 2010, from http://www.sph.emory.edu/ManagingEpilepsyWell/research/eprc_ webease.php Managing Epilepsy Well. (2010b). University of Washington: Adapting the PEARLS Program for Adults with Epilepsy. Retrieved January 12, 2010, from http://www.sph.emory.edu/ManagingEpilepsyWell/research/wash_pearls.php Martin, J. R. (1997). Mindfulness: A proposed common factor. [Journal; Peer Reviewed Journal]. Journal of Psychotherapy Integration, 7(4), 291-312. Mason, O., and Hargreaves, I. (2001). A qualitative study of mindfulness-based cognitive therapy for depression. Br. J. Med. Psychol, 74 Part 2, 197-212. Mauer, B. J., and Druss, B. G. (2009). Mind and Body Reunited: Improving Care at the Behavioral and Primary Healthcare Interface. J. Behav. Health Serv Res. McCagh, J., Fisk, J. E., and Baker, G. A. (2009). Epilepsy, psychosocial and cognitive functioning. Epilepsy Res, 86(1), 1-14. McDaid, D., Samyshkin, Y. A., Jenkins, R., Potasheva, A., Nikiforov, A., and Ali Atun, R. (2006). Health system factors impacting on delivery of mental health services in Russia: multi-methods study. Health Policy, 79(2-3), 144-152. McLaughlin, D. P., Pachana, N. A., and McFarland, K. (2008). Stigma, seizure frequency and quality of life: the impact of epilepsy in late adulthood. Seizure, 17(3), 281-287. Mendez, M. F., Doss, R. C., Taylor, J. L., and Salguero, P. (1993). Depression in epilepsy. Relationship to seizures and anticonvulsant therapy. J. Nerv. Ment. Dis, 181(7), 444-447. Mensah, S. A., Beavis, J. M., Thapar, A. K., and Kerr, M. (2006). The presence and clinical implications of depression in a community population of adults with epilepsy. Epilepsy Behav, 8(1), 213-219. Meredith, L. S., Orlando, M., Humphrey, N., Camp, P., and Sherbourne, C. D. (2001). Are better ratings of the patient-provider relationship associated with higher quality care for depression? Med. Care, 39(4), 349-360. Miller, L., and Rollnick, S. (2002). Motivational Interviewing (2nd ed.). New York: Guilford Press. Miller, W. (1995). Increasing motivation for change. In M. W. Hester RK (Ed.), Handbook of Alcoholism Treatment Approaches: Elective Alternatives (2nd ed., pp. 89-104). Boston: Allyn and Bacon. Mohr, D. C., Hart, S. L., Julian, L., Catledge, C., Honos-Webb, L., Vella, L., et al. (2005). Telephone-administered psychotherapy for depression. Arch. Gen. Psychiatry, 62(9), 1007-1014. Mohr, D. C., Likosky, W., Bertagnolli, A., Goodkin, D. E., Van Der Wende, J., Dwyer, P., et al. (2000). Telephone-administered cognitive-behavioral therapy for the treatment of depressive symptoms in multiple sclerosis. J. Consult. Clin. Psychol, 68(2), 356-361. Mojtabai, R. (2009). Unmet need for treatment of major depression in the United States. Psychiatr. Serv, 60(3), 297-305. Moussavi, S., Chatterji, S., Verdes, E., Tandon, A., Patel, V., and Ustun, B. (2007). Depression, chronic diseases, and decrements in health: results from the World Health Surveys. Lancet, 370(9590), 851-858. Olfson, M., Marcus, S. C., Druss, B., Elinson, L., Tanielian, T., and Pincus, H. A. (2002). National trends in the outpatient treatment of depression. Jama, 287(2), 203-209.
Depression in People with Epilepsy
285
Paradiso, S., Hermann, B. P., Blumer, D., Davies, K., and Robinson, R. G. (2001). Impact of depressed mood on neuropsychological status in temporal lobe epilepsy. J. Neurol. Neurosurg. Psychiatry, 70(2), 180-185. Patel, V. (2001). Cultural factors and international epidemiology. Br. Med. Bull, 57, 33-45. Penninx, B. W., Leveille, S., Ferrucci, L., van Eijk, J. T., and Guralnik, J. M. (1999). Exploring the effect of depression on physical disability: longitudinal evidence from the established populations for epidemiologic studies of the elderly. Am. J. Public Health, 89(9), 1346-1352. Pilling, S., Anderson, I., Goldberg, D., Meader, N., and Taylor, C. (2009). Depression in adults, including those with a chronic physical health problem: summary of NICE guidance. BMJ, 339, b4108. Prince, M., Patel, V., Saxena, S., Maj, M., Maselko, J., Phillips, M. R., et al. (2007). No health without mental health. Lancet, 370(9590), 859-877. Proudfoot, J., Ryden, C., Everitt, B., Shapiro, D. A., Goldberg, D., Mann, A., et al. (2004). Clinical efficacy of computerised cognitive-behavioural therapy for anxiety and depression in primary care: randomised controlled trial. Br. J. Psychiatry, 185, 46-54. Pruchno, R., Wilson-Genderson, M., and Cartwright, F. (2009). Self-rated health and depressive symptoms in patients with end-stage renal disease and their spouses: a longitudinal dyadic analysis of late-life marriages. J. Gerontol B Psychol. Sci. Soc. Sci, 64(2), 212-221. Ramaratnam, S., Baker, G. A., and Goldstein, L. H. (2008). Psychological treatments for epilepsy. Cochrane Database Syst Rev(3), CD002029. Rehman, U. S., Gollan, J., and Mortimer, A. R. (2008). The marital context of depression: research, limitations, and new directions. Clin. Psychol. Rev, 28(2), 179-198. Reisinger, E. L., and DiIorio, C. (2009). Individual, seizure-related, and psychosocial predictors of depressive symptoms among people with epilepsy over six months. Epilepsy Behav, 15(2), 196-201. Reisinger Walker, E., Obolensky, N., Dini, S., and Thompson, N. J. (Under review). Formative and process evaluations of a CBT and mindfulness intervention for people with epilepsy and depression. Resnicow, K., Jackson, A., Wang, T., McCarty, F., De, A. K., McCarty, F., et al. (2001). A motivational interviewing intervention to increase fruit and vegetable intake through Black churches: Results of the Eat for Life trial. American Journal of Public Health, 91(10), 1686-1693. Rubak, S., Sandbaek, A., Lauritzen, T., and Christensen, B. (2005). Motivational interviewing: a systematic review and meta-analysis. Br. J. Gen. Pract, 55(513), 305-312. Rubin, J. B. (1999). Close encounters of a new kind: Toward an integration of psychoanalysis and Buddhism. American Journal of Psychoanalysis, 59(1), 5-24. Rugulies, R. (2002). Depression as a predictor for coronary heart disease. a review and metaanalysis. Am. J. Prev. Med, 23(1), 51-61. Salize, H. J., Rossler, W., and Becker, T. (2007). Mental health care in Germany: current state and trends. Eur. Arch. Psychiatry Clin. Neurosci, 257(2), 92-103. Schmitz, E. B., Robertson, M. M., and Trimble, M. R. (1999). Depression and schizophrenia in epilepsy: social and biological risk factors. Epilepsy Res, 35(1), 59-68.
286
Elizabeth Reisinger Walker and Colleen DiIorio
Scott, R. A., Latoo, S. D., and Sander, J. W. A. S. (2001). The treatment of epilepsy in developing countries: where do we go from here? Bulletin of the World Health Organization, 79((4)), 344-351. Scrandis, D. A., Sheikh, T. M., Niazi, R., Tonelli, L. H., and Postolache, T. T. (2007). Depression after delivery: risk factors, diagnostic and therapeutic considerations. Scientific World Journal, 7, 1670-1682. Seelig, M. D., and Katon, W. (2008). Gaps in depression care: why primary care physicians should hone their depression screening, diagnosis, and management skills. J. Occup. Environ. Med, 50(4), 451-458. Segal, Z. V., Williams, J. M. G., and Teasdale, J. D. (2002). Mindfulness-based cognitive therapy for depression: A new approach to preventing relapse. New York: Guilford. Seminario, N. A., Farias, S. T., Jorgensen, J., Bourgeois, J. A., and Seyal, M. (2009). Determination of prevalence of depression in an epilepsy clinic using a brief DSM-IVbased self-report questionnaire. Epilepsy Behav, 15(3), 362-366. Shinfuku, N. (1998). Mental health services in Asia: international perspective and challenge for the coming years. Psychiatry Clin. Neurosci, 52(3), 269-274. Shneker, B. F., Cios, J. S., and Elliott, J. O. (2009). Suicidality, depression screening, and antiepileptic drugs: reaction to the FDA alert. Neurology, 72(11), 987-991. Simon, G. E., Barber, C., Birnbaum, H. G., Frank, R. G., Greenberg, P. E., Rose, R. M., et al. (2001). Depression and work productivity: the comparative costs of treatment versus nontreatment. J. Occup. Environ. Med, 43(1), 2-9. Simon, G. E., Ludman, E. J., and Rutter, C. M. (2009). Incremental benefit and cost of telephone care management and telephone psychotherapy for depression in primary care. Arch. Gen. Psychiatry, 66(10), 1081-1089. Simon, G. E., and VonKorff, M. (1991). Somatization and psychiatric disorder in the NIMH Epidemiologic Catchment Area study. Am. J. Psychiatry, 148(11), 1494-1500. Smeets, V. M., van Lierop, B. A., Vanhoutvin, J. P., Aldenkamp, A. P., and Nijhuis, F. J. (2007). Epilepsy and employment: literature review. Epilepsy Behav, 10(3), 354-362. Smith, A., Graham, L., and Senthinathan, S. (2007). Mindfulness-based cognitive therapy for recurring depression in older people: a qualitative study. Aging Ment. Health, 11(3), 346357. Smith, D. E., Heckemeyer, C. M., Kratt, P. P., and Mason, D. A. (1997). Motivational interviewing to improve adherence to a behavioral weight-control program for older obese women with NIDDM: A pilot study. Diabetes Care, 20(1), 52-54. Strine, T. W., Kroenke, K., Dhingra, S., Balluz, L. S., Gonzalez, O., Berry, J. T., et al. (2009). The associations between depression, health-related quality of life, social support, life satisfaction, and disability in community-dwelling US adults. J. Nerv. Ment. Dis, 197(1), 61-64. Sullivan, P. F., Neale, M. C., and Kendler, K. S. (2000). Genetic epidemiology of major depression: review and meta-analysis. Am. J. Psychiatry, 157(10), 1552-1562. Svenningsson, P., Chergui, K., Rachleff, I., Flajolet, M., Zhang, X., El Yacoubi, M., et al. (2006). Alterations in 5-HT1B receptor function by p11 in depression-like states. Science, 311(5757), 77-80. Swinkels, W. A., Kuyk, J., van Dyck, R., and Spinhoven, P. (2005). Psychiatric comorbidity in epilepsy. Epilepsy Behav, 7(1), 37-50.
Depression in People with Epilepsy
287
Szaflarski, J. P., and Szaflarski, M. (2004). Seizure disorders, depression, and health-related quality of life. Epilepsy Behav, 5(1), 50-57. Teasdale, J. D., Segal, Z. V., Williams, J. M., Ridgeway, V. A., Soulsby, J. M., and Lau, M. A. (2000). Prevention of relapse/recurrence in major depression by mindfulness-based cognitive therapy. J. Consult. Clin. Psychol, 68(4), 615-623. Thapar, A., Roland, M., and Harold, G. (2005). Do depression symptoms predict seizure frequency--or vice versa? J. Psychosom. Res, 59(5), 269-274. Thompson, N. J., Walker, E. R., Obolensky, N., Winning, A., Barmon, C., DiIorio, C., et al. (Under review). Distance Delivery of Mindfulness-based Cognitive Therapy for Depression: Project UPLIFT. Journal of consulting and clinical psychology. Tomlinson, M., Grimsrud, A. T., Stein, D. J., Williams, D. R., and Myer, L. (2009). The epidemiology of major depression in South Africa: results from the South African stress and health study. S. Afr. Med. J, 99(5 Pt 2), 367-373. Tracy, J. I., Dechant, V., Sperling, M. R., Cho, R., and Glosser, D. (2006). The association of mood with quality of life ratings in epilepsy. Neurology. Unutzer, J., Katon, W., Callahan, C. M., Williams, J. W., Jr., Hunkeler, E., Harpole, L., et al. (2002). Collaborative care management of late-life depression in the primary care setting: a randomized controlled trial. Jama, 288(22), 2836-2845. Ustun, T. B., Ayuso-Mateos, J. L., Chatterji, S., Mathers, C., and Murray, C. J. (2004). Global burden of depressive disorders in the year 2000. Br. J. Psychiatry, 184, 386-392. Vicente, B., Kohn, R., Rioseco, P., Saldivia, S., Levav, I., and Torres, S. (2006). Lifetime and 12-month prevalence of DSM-III-R disorders in the Chile psychiatric prevalence study. Am. J. Psychiatry, 163(8), 1362-1370. Vilhjalmsson, R. (1998). Direct and indirect effects of chronic physical conditions on depression: a preliminary investigation. Soc. Sci. Med, 47(5), 603-611. Vittengl, J. R., Clark, L. A., Dunn, T. W., and Jarrett, R. B. (2007). Reducing relapse and recurrence in unipolar depression: a comparative meta-analysis of cognitive-behavioral therapy's effects. J. Consult. Clin. Psychol, 75(3), 475-488. Weissman, M. M., Bland, R. C., Canino, G. J., Faravelli, C., Greenwald, S., Hwu, H. G., et al. (1996). Cross-national epidemiology of major depression and bipolar disorder. Jama, 276(4), 293-299. Wiebe, S., Bellhouse, D. R., Fallahay, C., and Eliasziw, M. (1999). Burden of epilepsy: The Ontario Health Survey. Canadian Journal of Neurological Sciences, 26(4), 263-270. Wiegartz, P., Seidenberg, M., Woodard, A., Gidal, B., and Hermann, B. (1999). Co-morbid psychiatric disorder in chronic epilepsy: recognition and etiology of depression. Neurology, 53(5 Suppl 2), S3-8. Wright, J. H., Wright, A. S., Albano, A. M., Basco, M. R., Goldsmith, L. J., Raffield, T., et al. (2005). Computer-assisted cognitive therapy for depression: maintaining efficacy while reducing therapist time. Am. J. Psychiatry, 162(6), 1158-1164. Zlotnick, C., Kohn, R., Keitner, G., and Della Grotta, S. A. (2000). The relationship between quality of interpersonal relationships and major depressive disorder: findings from the National Comorbidity Survey. J. Affect. Disord, 59(3), 205-215.
In: Society, Behaviour and Epilepsy Editors: Jaya Pinikahana and Christine Walker
ISBN 978-1-61761-001-1 © 2011 Nova Science Publishers, Inc.
Chapter XVI
Epilepsy in the Elderly: Diagnostic Approach and Treatment Sophie Dupont 1, B. De Toffol, 2Marc Verny 3, and Caroline Hommet 4
1. Unité d‘Epileptologie, Clinique Neurologique Paul Castaigne, Hôpital de la Salpêtrière, Paris, France 2. Service de Neurologie, CHU Tours et université F Rabelais, Tours 3. Centre de Gériatrie, Groupe hospitalier Pitié-Salpétrière, assistance publique-hôpitaux de Paris and Université Pierre et Marie Curie, Paris, France 4. Médecine Interne Gériatrique et CMRR, CHU Tours et université F Rabelais, Tours
Abstract Epilepsy is defined as a chronic illness, diagnosed after the occurrence of two or more unprovoked seizures (seizures which occur without any obvious immediate cause) and must be differentiated from acute symptomatic seizures (which are provoked by acute illnesses) in order to avoid confusing data on dementia. Recognizing and correctly diagnosing late-onset seizures in the elderly may be challenging for various reasons: limited knowledge of seizure symptoms in this age group, multiple conditions that may mimic seizures such as transient ischemic attacks, stroke, syncope, sleep disorders and toxic or metabolic disturbances. When seizures are suspected, there is often limited access to specific diagnostic tools such as video-EEG, or an absence of witnesses so that diagnosis is not easily confirmed. Epilepsy is particularly complex in older people since they Correspondence: Associate Professor Sophie Dupont, Unité d‘Epileptologie, Clinique Neurologique Paul Castaigne, Hôpital de la Salpêtrière, 47, boulevard de l‘Hôpital, 75651 Paris cedex 13, France. E-mail:
[email protected].
290
Sophie Dupont, B. De Toffol, Marc Verny et al.
are more likely to have co-morbidities than younger individuals. Antiepileptic drugs (AEDs) should be started only after the diagnosis is clearly established, when the risk of recurrence is high and using mono-therapy whenever possible. Treatment must be adapted to the particular susceptibility of elderly subjects. Although little data are available, the newer AEDs offer significant advantages over older medications in this context.
Keywords: elderly, epilepsy, dementia, antiepileptic drugs
Epilepsy in the Elderly: Frequent but Under-diagnosed Both unprovoked and acute symptomatic seizures are common in the elderly.The incidence of any type of first seizure increases with age: from 50 per 100, 000 in persons aged 40-59 years to 127 per 100, 000 in those older than 60 years.(Hauser et al., 1993) The prevalence steadily increases with age and is estimated to be 5/1000 between 20 to 50 years, 7/1000 between 55 to 64 years and 12/1000 between 85 to 94 years.(Hauser et al., 1996) The four most common aetiologies for seizures in the elderly are cerebrovascular disease, toxic and metabolic disorders, dementia and brain tumour (Granger et al., 2002; Hauser et al., 1996). Cerebrovascular disease is a predisposing factor for seizures in the elderly and is related to the anatomical lesions of the disease and to co-morbidities particularly vascular pathologies and poly-medication. The annual incidence of epilepsy, defined as the occurrence of at least two unprovoked seizures separated by an interval of more than one day, increases from 110 per 100,000 in people between the ages of 65 and 69 to more than 160 per 100,000 in those over 80 (de la Court et al., 1996; Faught, 1999; Hauser, 1992; Luhdorf et al., 1986a). Certain particularities should be considered in aging. For instance, aging itself is a common factor for both epilepsy and dementia. Cerebrovascular disease is the major aetiology of epilepsy in the elderly, accounting for up to 50% of cases in subjects aged ≥ 65 year. Dementia, particularly Alzheimer‘s Disease (AD), accounts for 9 to 17% of the epilepsies seen in the elderly (Granger et al., 2002 ; Hauser, 1992; Hauser et al., 1993; Hauser et al., 1996; Hesdorffer et al., 1996; Jallon et al., 2001; Stephen and Brodie, 2000). Although AD is the most common form of dementia, other causes include, in descending order, vascular disease, Lewy Body disease and frontal lobe dementia (Lobo et al., 2000) but data are very sparse concerning incidence or prevalence of seizures in these other dementia. Most studies on dementia have retrospectively evaluated the prevalence of epileptic seizures in patients with autopsy-proven AD (Hauser et al., 1986; Mendez et al., 1994; Romanelli et al., 1990). A diagnosis of AD is associated with an increased risk of unprovoked seizures ranging from 9 to 26% compared to non-demented, similar-aged subjects (Hauser 1986). Mendez , 2003) reported that 10-22% of AD patients have at least one unprovoked seizure. In a study in a psychiatric population aged > 55 years with dementia (most suffering from AD but some with vascular dementia), McAreavey et al (1992) reported that 9% of the patients had experienced seizures. Although theses studies are interesting, they all contained various methodological caveats such as particularly small sample sizes in the neuro-pathological
Epilepsy in the Elderly: Diagnostic Approach and Treatment
291
studies, no systematic evaluation of clinical variables, the absence of imaging studies or a selection bias. In an observational study describing first seizures in a sample of elderly subjects with AD hospitalized in an acute geriatric care unit, Hommet et al (2007) reported that 2,5 % of the hospitalized AD patients were admitted for a first seizure. Recently, in a retrospective study (Rao 2009) concerning elderly subjects with dementia, seizures were described in 3,6%. Neuroimaging revealed vascular lesions in more than a third of subjects. In a prospective study, Scarmeas (2009) evaluated the incidence of new-onset unprovoked seizures in four hundred and fifty three patients with probable AD who had been observed prospectively from mild disease stages. Only 1.5 % developed seizures during 5 years of follow-up. Interestingly, age was inversely linked to the risk of seizures. Brain trauma and brain tumours each accounted for 20% of the cases of epilepsy (Brodie et al., 2009).
Epileptic Seizures in the Elderly: Physical Diagnosis The diagnosis of epileptic seizures in the elderly patient remains challenging for a variety of reasons including the fact that these types of seizures differ from those seen in younger patients and that their clinical presentation can be misleading (Van Cott, 2002).
Seizure Type In contrast to children, the majority of elderly patients who have seizures experience partial seizures, in particular complex partial seizures. Generalized-onset seizures (mainly tonic-clonic seizures) may also occur, as a result of environmental factors (provoked seizures) or as a result of diffuse cerebral change with age or degenerative disease. Status epilepticus, mostly complex partial status epilepticus (Waterhouse and DeLorenzo, 2001) or more rarely ―de novo‖ late onset absence status epilepticus (Thomas et al., 1992) also seem more frequent in this age group.
Clinical Presentation of Seizures Partial Seizures Partial seizures in older patients are less likely to have the classical clinical manifestations suggesting epilepsy. While temporal lobe seizures are the more frequent focal seizures in adult patients, frontal lobe seizures seem particularly common in older patients. This may be related to the fact that cerebrovascular disease is the most common cause of seizures in the elderly, and that strokes usually involve extratemporal regions. In addition, frontal lobe hypothesis in the elderly (Kalpouzos et al., 2008; West, 1996; Willis et al., 2002; Yanase et al., 2005) may be another hypothesis. The consequences of this condition could lead to a state of fragility. Auras are less frequent and when they exist, are often non-specific (dizziness and asthenia). Complex partial seizures are often described as altered mentation,
292
Sophie Dupont, B. De Toffol, Marc Verny et al.
periods of staring, unresponsiveness or blackout spells. Automatisms are less frequent whereas inhibitory symptoms seem more frequent. When the clinical presentation is nottypical, post-ictal manifestations such as amnesia and transient confusion are of particular diagnostic interest. A recent study that compared the clinical characteristics and the electroencephalographic (EEG) findings in 25 patients with an inhibitory seizure to those in 252 patients with a transient ischemic attack pointed out that a short temporary speech disturbance with partial amnesia for the event was very suggestive of seizures (De Reuck and Van Maele, 2009). Inhibitory post-ictal symptoms are also frequently described: confusion, a cognitive defect or paresis and may be unusually prolonged often lasting several days (Ramsay and Pryor, 2000). However, confusion is frequent in older patients after prolonged syncope or other significant transient medical manifestations, notably in cases of pre existent cognitive disturbances. Tonic-Clonic Seizures Primary or secondarily generalized tonic-clonic seizures are not clinically different in the elderly (loss of consciousness with an initial tonic phase followed by a clonic phase). But like all tonic-clonic seizures, they may be hard to diagnose when they are un-witnessed. In the absence of a witness, the clinical manifestations may be limited to an unusual tiredness, a history of fall with loss of consciousness, transient amnesia, or prolonged confusion that resolves spontaneously. It has been suggested (Sirven and Ozuna, 2005) that secondarily generalized tonic-clonic seizures are less frequent in older patients because partial seizures are less likely to spread to adjacent areas of the brain, except in patients with Alzheimer‘s disease. Status Epilepticus Non-convulsive status epilepticus is particularly frequent in older patients (Waterhouse and DeLorenzo, 2001) and should be systematically considered as a cause of unexplained coma or a persistently confused state even in the absence of any previous seizure history (Brodie et al., 2009). Clinical manifestations may be more subtle: altered mentation and unusual behaviour, often associated with minor motor manifestations such as focal myoclonic or clonic seizures. In all cases, an EEG is essential for the diagnosis of non-convulsive status epilepticus. ―De novo‖ late onset absence status epilepticus (Thomas et al., 1992) has been described in elderly patients who had abruptly discontinued their anxyolytic or sedative drugs These patients often presented other epileptogenic cofactors including excessive use of other psychotropic drugs, nonpsychotropic treatment, hypocalcemia, hyponatremia, and chronic alcoholism. Typically, absence status epilepticus occured in middle-age patients who had no history of epilepsy. The clinical and EEG presentation were similar to those seen in absence status occurring in patients with prior epilepsy: confusion, altered mentation and generalized spike-wave discharges on EEG. All the episodes were resolved without recurrence with the intra-venous injection of benzodiazepins and the long-term administration of anticonvulsant medication was not required.
Epilepsy in the Elderly: Diagnostic Approach and Treatment
293
Diagnostic Approach Seizure-Type Approach Instead of a Syndromic Approach In children and younger adults, the International Classification of the Epilepsies and Epileptic Syndromes is a useful tool for classifying epilepsies and has major therapeutic and prognostic implications (1989). The current classification is based on clinical, electroencephalographic and aetiological criteria that provide a definition of distinct syndromes with a common clinical presentation, and prognosis. Epileptic syndromes are classified according to their topography (focal, generalized, or undetermined) and to their presumed aetiology (idiopathic, cryptogenic, or symptomatic). Its widespread utilisation has contributed much to the current understanding of epilepsy. It is now well known that inappropriate anti-epileptic drugs may worsen seizures and that defining the type of epileptic syndrome may provide a useful guide for selecting the appropriate treatment. The syndrome classification also offers major prognostic information that may be useful to practitioners and their patients. The diagnostic approach in the elderly is different from that in children or adult patients, in whom epileptic syndromes can be easily recognized and treated. In the elderly, the syndromic approach is not appropriate for several reasons: 1) Seizures in the elderly are often single (so-called acute or provoked seizures). Numerous epidemiological studies have shown that the incidence of acute or provoked seizures increases linearly with each decade of advancing age (Hauser, 1997; Hauser et al., 1993). 2) Single or recurrent seizures in the elderly are mostly symptomatic and often have multiple concomitant causes. The development of seizures frequently depends on a combination of predisposing, non-modifiable factors such as sequellae from stroke or baseline dementia—and/or precipitating, often modifiable factors—such as hypoglycemia, hyponatremia, the abrupt discontinuation of anxyolytic or sedative drugs, acute stroke or trauma, medications that lower the seizure threshold. 3) Idiopathic generalized epilepsies are exceptional in the elderly It therefore seems more appropriate to reason in terms of seizures-types rather than in terms of epileptic syndromes in older patients.
When should We Consider the Diagnosis of Seizures? Elderly people are often referred to emergency departments or to geriatricians for nonspecific symptoms: acute confusion, falls, loss of consciousness, a focal neurological deficit, sleep disorders, behavioural or psychiatric disorders. Seizures should be systematically considered as a potential cause for these non-specific symptoms. Acute Confusional State Acute confusion or so-called delirium is a common reason for geriatric consultation in the emergency department; they also affect an estimated 14–56% of all hospitalized elderly
294
Sophie Dupont, B. De Toffol, Marc Verny et al.
patients (Inouye, 1998). Classically the clinical presentation includes altered mentation with frequent hallucinations or delusions associated with agitation or sedation (Fong et al., 2009). Dementia remains the most prominent risk factor for delirium since two-thirds of all cases of delirium in this age-group occurs in patients with dementia. The causes are often multifactorial and occur in a context of cognitive dysfunction. However the difficulty is that non-epileptic delirium and seizure activity can coexist and share the same causative factors. The clinical history, physical examination and laboratory tests can most often point to the most likely etiologies of acute confusion, such as medications (especially drugs with anticholinergic potential), infections and electrolyte disturbances. However, potential causes of confusion also include acute neurological events and especially seizures with two main clinical presentations: ictal confusion due to non-convulsive status epilepticus or post-ictal confusion that may last as long as 1-2 weeks in an elderly patient, while only lasting a few minutes in younger individuals. In non-convulsive status epilepticus, subtle motor activity may be present and may suggest the diagnosis. In contrast, myoclonus or asterixis are not pathognomonic of seizures and may only reflect a concomitant encephalopathy, resulting in further diagnosis difficulty. In all cases, an EEG is essential and will help establish the diagnosis of non- convulsive status epilepticus. Prolonged post-ictal confusion is more difficult to diagnose and the history is essential. In addition, some clinical symptoms may help distinguish non-epileptic delirium from post-ictal confusion: the existence of complex visual hallucinations, the long duration of the symptom (weeks to months), the fluctuating course of delirium which is often worse at night. Unfortunately, in the vast majority of cases, an EEG will not be very helpful since it often only shows moderate to severe background slowing. Falls Falls pose a serious health problem for older persons since they occur in 30% of adults over age 65 and 40% over age 80. Accidental falls due to extrinsic factors such as poor lighting, throw rugs and other environmental hazards may be easily eliminated. Intrinsic causes of falls are numerous and include changes associated with aging, orthostatic hypotension, many medications, delirium, anaemia, diabetes mellitus, Parkinson's disease, depression, cognitive impairment, syncope and partial complex seizure .(Morley, 2007). Falls linked to mechanisms that maintain postural stability (balance, gait speed and cardiovascular function) can usually be eliminated by a careful cardiovascular and neurological examination. In all cases, the physical examination should focus upon the presence of orthostatic hypotension, testing visual acuity, a hearing assessment, and carotid sinus hypersensitivity which contribute to unexplained falls (De Breucker et al., 2007). The diagnosis of seizures should only be suspected if the fall is associated with impairment or loss of consciousness or amnesia after the fall. In these later cases, further investigations including one or several EEG‘s and an ECG will be mandatory. Loss of Consciousness When loss of consciousness is firmly established, the two primary differential diagnoses are syncope and epilepsy. Syncopal episodes are common amongst older adults; and their causes can either be benign or life-threatening (Mendu et al., 2009). The most frequent etiologies of syncopes are cardiogenic syncope (arrythmias or conduction disturbances), obstructive vascular syncope (aortic stenosis), orthostatic syncope, and neurologically
Epilepsy in the Elderly: Diagnostic Approach and Treatment
295
mediated syncope (vasovagal syncopes and carotid sinus hypersensitivity). The major priority is to exclude a life- threatening cardiac disease like arythmia or auriculo-ventricular block. The history and clinical symptoms may suggest a syncope rather than a seizure when certain precipitating factors are present like violent pain or fear, head turning or wearing garments with tight-fitting collars, orthostatic hypotension, coughing, micturition or defecation. The absence of prodromal symptoms or prolonged prodromal symptoms including dizziness, nausea or vomiting, vertigo, a brief loss of consciousness without symptoms followed by no amnesia or confusion or a brief episode of confusion or amnesia are also suggestive of syncopes. In the presence of a loss of consciousness associated to myoclonic jerks, tonicclonic seizure have to be differentiated from convulsive syncope. The brief duration of the myoclonic jerks, the existence of vasovagal prodromal symptoms occurring before the loss of consciousness and the absence of prolonged confusion or amnesia after the episode constitutes strong arguments against the diagnosis of seizure. If syncope is suspected, the following procedures seems to be the most useful and cost-effective: carotid sinus massage (auscultation for a carotid artery bruit is mandatory prior to performing carotid sinus massage) or Valsalva maneuver, verifying postural blood pressure and electrocardiogram telemetry. Once again, the difficulty is that syncope and seizures may share common pathophysiological mechanisms and that a prolonged syncope may precipitate a generalized tonic-clonic seizure, leading to diagnostic uncertainty. When doubt persists, both an ECG and an EEG are required. Focal Neurological Deficit As we shall see below, partial seizures in the elderly may be manifested by inhibitory symptoms. The key point here is the duration of focal symptoms: a shorter duration (less than 5 minutes) is suggestive of seizures rather than a transient ischemic attack (Sirven and Ozuna, 2005). However, seizures related to previous strokes may cause prolonged post-ictal deficits mimicking a new episode of stroke. In this case, diffusion MRI is needed to exclude a recurrent vascular episode. Sleep Disorders In the elderly, sleep complaints often coexist with other medical and psychiatric disorders and can be associated with the medications used to treat those illnesses or be related to changes in the patient‘s circadian rhythm or other sleep disorders (Ancoli-Israel et al., 2008). Common sleep disorders that can mimic frontal lobe seizures include periodic limb movements during sleep, the rapid eye movement sleep behaviour disorder and sometimes the restless legs syndrome (Martin et al., 2000). Patients who suffer from periodic limb movements during sleep or the rapid eye movement sleep behaviour disorder typically complain of insomnia and excessive daytime sleepiness and when they have a bed partner, he or she reports the sudden onset of brief leg kicks, sometimes associated with shouting or swearing in cases of the rapid eye movement sleep behaviour disorder. The prevalence of these sleep-disorders increases with age and they may be associated with sleep disorders of breathing. Clinically, they must be distinguished from nocturnal frontal lobe seizures that are often characterized by sudden and violent automatisms during sleep. However, nocturnal frontal lobe seizures usually begin at an earlier age and often cluster. If the age of onset of the sleep disorder cannot be clearly established, the clinical diagnosis will require nocturnal
296
Sophie Dupont, B. De Toffol, Marc Verny et al.
polysomnography. The restless-legs syndrome is a related disorder in which patients complain of an unpleasant sensation in their legs which is only relieved by movements. It does not really mimic seizures and the diagnosis is based on history.
Diagnostic Tools Common Diagnostic Evaluation An understanding of the features that distinguish epilepsy from other disorders is the key point in establishing the diagnosis of seizures. In adult patients, the diagnosis is mainly based on a thorough history obtained from both the patient and available witnesses. A comprehensive neurologic examination may also be useful in some cases. Table 1. General diagnostic approach
Epilepsy in the Elderly: Diagnostic Approach and Treatment
297
The typical diagnostic evaluation should also include routine serum laboratory tests, EEG and cerebral MRI. In older patients, additional features must be taken into account: the absence of a reliable history (cognitive impairment; limited history available and no witness), seizures with a non-specific presentation (confusion, falls, loss of consciousness, sleep disorder), and common disorders that may clinically imitate seizures and that are potentially more frequent in this age group (syncope, transient ischemic attacks, cardiovascular disease). In these situations, additional tests (especially cardiac and cerebrovascular assessments) are often necessary in elderly people (see table 1). Table 2. Diagnostic tool based on a combination of criteria for the diagnosis of seizures in the elderly Major Criteria
Minor criteria
- Impairment of consciousness with automatisms - Confusional state with sudden onset and end - Rhythmic muscular contractions in a focal territory - Paroxysmal behavioral disorder associated with a focal neurological sign - Prolonged confusion - Prolonged or aggravated focal neurological deficit - Bite of the lateral side of the tongue
- Impairment of consciousness - Diurnal or nocturnal paroxysmal movement disorders including diffuse myoclonias - Isolated paroxysmal behavioral disorder - Focal neurological deficit
History
- Alzheimer disease - Recurrence of stereotyped and identical episodes
Precipitating factors
Benzodiazepines withdrawal Alcohol withdrawal Hypoglycemia
History of epilepsy Alcohol abuse Dementia other than Alzheimer disease - Iatrogenicity (especially psychotropic drugs) Acute metabolic disorder
Clinical signs
Certainty Criteria - Generalized tonic-clonic seizure with a witness
Post-ictal signs
EEG Imaging
- Seizure on EEG
- Spikes and wave-spikes - Cortical focal lesion (recent or sequellae)
- Unusual asthenia - Diffuse myalgia
- Focal slow waves - Other cerebral lesions
298
Sophie Dupont, B. De Toffol, Marc Verny et al.
Specific Diagnostic Evaluation In a recent study (Dupont et al., 2009), we proposed a diagnostic scale to help physicians in clinical practice recognize seizures better and to orient elderly patients more efficiently. A multidisciplinary group composed of neurologists and geriatricians worked together to elaborate an electro-clinical score designed to help establish the diagnosis of seizures in elderly patients in different clinical settings. The diagnostic algorithm was based on clinical, electroencephalographic and radiological criteria (certainty criteria, major criteria and minor criteria explicitly linked to the supporting evidence and graded according to the strength of that evidence (see table 2). Each patient complaining of impaired consciousness, diurnal or nocturnal paroxysmal movement disorders, paroxysmal behavioral disorders, a transient focal neurological deficit, a fainting spell, a fall, confusion, unconsciousness, nocturnal agitation or psychiatric-like disorders who has undergone an EEG and/or a CT-scan or a MRI can be evaluated by this diagnostic algorithm. The algorithm classified patients into four categories: certain epileptic seizures, highly probable epileptic seizures, possible epileptic seizures, improbable (unlikely) epileptic seizures. Of course, this diagnostic tool requires an additional prospective validation (retrospective validation has already been performed) but similar diagnostic approaches should be encouraged
Video-EEG Video-EEG monitoring is the gold standard method for diagnosis of seizures. This method is clearly underused in the elderly population, partly because the elderly represent a small percentage of admissions for epilepsy monitoring units and partly because these monitoring units are usually reserved for the presurgical evaluation of refractory younger epileptic patients. There is a real need to develop specific video-EEG monitoring units located in geriatric units and allocated to the diagnosis of seizures or other events mimicking seizures.
Pitfalls Cognitive dysfunctionA decline in cognitive function is common with advanced age, and may represent an additional difficulty for the diagnosis of seizures (see chapter below). In contrast, seizures are a frequent manifestation occurring during the course of dementia, especially Alzheimer‘s disease and repeated temporal lobe seizures may mimic a dementia. Psychogenic Features It must be kept in mind that even older people may encounter psychogenic events. In a recent study, (Abubakr and Wambacq, 2005)) studied the results of video-EEG monitoring in elderly patients admitted for diagnosis of paroxysmal events or characterization and localization of supposed seizures. Among the 58 patients admitted, six had psychogenic nonepileptic seizures, 26 had physiological events; only 26 patients were diagnosed with real epileptic seizures. Psychogenic non-epileptic seizures typically occur in young females and are considered to be rare in the elderly. Nevertheless, recent studies (Lancman et al., 1996; McBride et al., 2002) have revealed that psychogenic non-epileptic seizures were consistently
Epilepsy in the Elderly: Diagnostic Approach and Treatment
299
found in older people who underwent video-EEG monitoring. The true prevalence of psychogenic non-epileptic seizures is unknown in the elderly and requires further prospective studies. Social or Familial Isolation The key to the diagnosis of a seizure is a witnessed description of the episode (Sirven and Ozuna, 2005). Unfortunately, elderly people are more likely to have unwitnessed seizures since they no longer work, are less active socially and often live alone. EEG There are two pitfalls with EEG interpretation in the elderly: firstly benign EEG changes are frequently associated with normal aging and may be misinterpreted as indicating a seizure tendency (Van Cott AC, 2002) and secondly, pathological EEG figures such as Periodic lateralized epileptiform discharges (PLEDs) reflecting underlying neurological diseases may be present and confused with epileptic discharges. Benign EEG Changes Associated with Aging The EEG‘s of elderly individuals have a high incidence of intermittent focal slowing, especially in the left temporal region of the brain. In addition, three benign epileptiform EEG variants that may be confused with epileptic discharges are more frequent in the elderly population: the so-called wicket spikes (spikes occurring in both the awaked state and during light sleep with a frequency of 6-11 Hz, usually in short runs (wicket rhythm) but also as single sharp transients; small sharp spikes (SSSs) (also known as benign epileptiform transients of sleep, SSSs which occur in light sleep (stages I and II of non-rapid eye movement sleep), usually sporadically) and subclinical rhythmic electrographic discharge in adults or SREDA (uncommon pattern observed mainly in older persons (>50 y) which may occur at rest or during drowsiness. SREDA superficially resembles an EEG seizure pattern. The frequency is typically 5-6 Hz and the location is widespread or bilateral and predominately posterior. The morphology is seizure-like (ie, rhythmic sharply contoured theta) and the abruptonset and termination may help distinguish SREDA from an EEG seizure. The duration ranges from 20 seconds to minutes (average 40-80 s)) (Benbadis and Rielo, 2008; Gibbs and Fa, 1952). PLEDs (PLEDs) are a well-defined electroencephalographic entity which has been recognized for the past four decades (Fitzpatrick and Lowry, 2007). PLEDs have been associated with both partial and generalized seizures, and typically with status epilepticus but also with a variety of conditions including cerebrovascular accidents, viral encephalitis, subdural hematoma, metabolic abnormalities, mitochondrial encephalomyopathy, diffuse neurocysticercosis and neurosyphilis. Their presence is not pathognomonic of epilepsy.
300
Sophie Dupont, B. De Toffol, Marc Verny et al.
Epilepsy in Dementia AD is Associated with an Increased Risk of Seizure In AD, the nature of the underlying mechanism for unprovoked seizures remains unclear. The role of the accumulation of amyloid plaques, neurofibrillary tangles and extensive neuronal cell loss in limbic and association cortices has been suspected (Armon et al., 2000; Forstl et al., 1992; Mendez and Lim, 2003; Palop et al., 2007). However, clinical studies which compared AD patients with and without seizures reported no more differences with respect to other medical disorders they had, the medications they took or the degree of focal pathology (Mendez et al., 1994; Romanelli et al., 1990) The role of a disproportionate neuronal degeneration in different brain areas has been postulated to be the neuropathological substrate of seizures in AD.(Forstl et al., 1992) In fact, for 6 patients with generalized motor seizures among 56 with autopsy-proven AD, (Forstl et al., 1992) reported significantly reduced pyramidal cell counts in the parietal and hippocampal areas. However, cell-loss may not be the only pathological basis for seizures in AD. The accumulation of amyloid plaques may also play a role as it was reported by Palop 2007, in human amyloid precursor protein (hAPP) transgenic mice (Palop et al., 2007). hAPP mice with high Aß levels have spontaneous nonconvulsive seizure activity in cortical and hippoocampal networks, suggesting the excitatory effect of Aß on these networks. Additional evidence for the role of neuropathological lesions is the report of seizures in familial AD, with early onset of the disease, linked to mutations in presenilin-1 (Singleton et al., 2000; Takao et al., 2001) (Shrimpton et al., 2007; Velez-Pardo et al., 2004) and with APP duplications (Cabrejo et al., 2006). A relationship between cell loss in the CA1 field of the hippocampus, a high density of A plaques and neurofibrillary tangles, and seizures have been postulated in patients with familial AD. So hippocampal lesions may be a susceptibility factor. However it does not constitute the only explicative factor because it is present in all subjects. Neuronal death may consequently affect GABAergic inhibitory circuits and the balance between excitation and inhibition which may induce seizures. (Mendez et al., 1994) In addition, seizures can also result from non-AD lesions like cerebrovascular lesions (Luhdorf et al., 1986b) or metabolic or neurotransmitter disorders (Mendez et al., 1994), in addition with polymedication, co-morbidities, behavioural symptoms with the use of psychotrope treatment Diagnosis of Seizures in Dementia The diagnosis of seizures and epilepsy may be particularly difficult in elderly patients with dementia. In AD generalized seizures are common and presumably generalize secondary to a partial seizure focus (Hauser et al., 1986; McAreavey et al., 1992; Mendez et al., 1994; Risse et al., 1990). Complex partial status epilepticus (Armon et al., 2000) and myoclonus, often a late manifestation (Hauser et al., 1986), have been reported. In older people with dementia, clinicians may mistakenly consider seizure activity (particularly complex partial seizures) to be symptomatic of the underlying dementia (Hommet et al., 2008). Indeed, partial seizures may result in a decline in cognitive functions, a worsening in the performance of activities of daily living and episodes of confusion.(Rabinowicz et al., 2000). It can also produce non-specific symptoms like dizziness, altered mental status or unresponsiveness. The diagnosis of a seizure is essentially a clinical diagnosis, based on a reliable history and is more difficult in demented patients since they often remember little of the episode.
Epilepsy in the Elderly: Diagnostic Approach and Treatment
301
Accordingly, corroborative evidence from the care-giver or an observer is important. The physical examination should be centered on the past medical history and the neurological and cardiovascular systems. Some specific features should be kept in mind in aging and dementia. Post- ictal confusion may last hours or even days (Ramsay et al., 2004). Focal motor deficits may last several hours, erroneously suggesting ischemic stroke and tongue-biting and urinary incontinence may be absent.(Stephen and Brodie, 2000) It is important to look for the use of medications that lower the seizure threshold but may cause acute seizures: typical and atypical anti-psychotics usually prescribed in AD (Centorrino et al., 2004), tricyclic antidepressants, theophylline and antibiotics like quinolones. A few seizures have been reported during treatment with cholinesterase inhibitors (Babic and Zurak, 1999; Piecoro et al., 1998). Just when during the course of AD seizures first occur has not been established. According to some authors, seizures occur in the later stages, 6 or more years after the onset of the dementia (Mendez et al., 1994; Piecoro et al., 1998; Risse et al., 1990) and the incidences of seizures increases with the severity of the dementia. (Hesdorffer et al., 1996; McAreavey et al., 1992; Mendez and Lim, 2003). Other authors have reported seizures at any time during the course of the illness (Hauser et al., 1986) including the early stage (as early as 3 months after the onset of AD) (Hesdorffer et al., 1996; Lozsadi and Larner, 2006). Furthermore, researchers have not found association between seizures and patient-age at the onset of AD nor any prior EEG findings (Romanelli et al., 1990). More recently, Amatniek et al (2006) evaluated its cumulative incidence and identified co-morbid medical and psychiatric baseline conditions that can influence the risk of unprovoked seizures in mild AD patients who were prospectively followed at 6-month intervals (median follow-up period of nearly 6 years). The cumulative incidence of unprovoked seizures at 7 years was almost 8%. Independent predictors of unprovoked seizures were younger age, African-American ethnic background, more severe dementia and focal epileptiform activity on EEG. More recent studies confirmed that younger age is associated with higher risk of seizures in AD (Amatniek et al., 2006; Scarmeas et al., 2009).
Seizures and Epilepsy in Non Alzheimer Dementia The risk of seizure is not limited to AD but there are little data concerning other types of dementia (Volpe-Gillot, 2007). In frontotemporal dementia, Nearly et al (1998) and Sperfeld et al., (1999) reported a novel phenotype characterized by the early onset of rapidly progressive frontotemporal dementia and parkinsonism with epileptic seizures linked to chromosome 17 (Foster et al., 1997). Unfortunately, there are no data about the prevalence of epileptic disorders in Lewy Body Disease. Vascular disease is the main aetiology of epilepsy in theelderly. However, there are no data on epilepsy in vascular dementia. Vascular dementia refers to various vascular diseases according to aetiology (ischemic or haemorrage), or topography (cortical/infracortical). All these pathologies are called vascular cognitive impairment (VCI) describing cognitive impairment with or without dementia in relation to vascular disease (Moorhouse and Rockwood, 2008; O'Brien et al., 2003). Many studies have addressed post-stroke epilepsy (Granger et al., 2002; Hauser and Kurland, 1975).
302
Sophie Dupont, B. De Toffol, Marc Verny et al.
The overall incidence of cerebrovascular-related seizures is estimated to be between 3.6 to 8.9% (Benbir et al., 2006; Reith et al., 1997). Some authors have individualized predictors of late-onset seizures and epilepsy such as the severity of the initial neurological impairment (Bladin et al., 2000; Reith et al., 1997) and the presence of a large cortical infarct on brain CT scan (Burn J, 1997; Lamy et al., 2003; Reith et al., 1997; So et al., 1996).The role of subcortical lesions as an aetiological factor of seizures in the elderly is questionable (De Reuck et al., 2007). Perhaps subcortical vascular lesions leads to fraily condition. Some specific conditions which can also be associated dementia and seizures must be considered. In Hashimoto encephalopathy (HE) authentic epileptic seizures (primary or secondary generalized seizures) have been reported in HE patients even if status epilepticus has only rarely been described. Various EEG abnormalities have also been described and usually non-specific (diffuse slowing, mesial temporal lobe epileptic foci during ictus, diffuse slowing with triphasic discharges) (Archambeaud et al., 2001). In the initial presentation of sporadic Creutzfeldt-Jakob disease (CJD), seizures rarely occur but are often resistant to AEDs (Aronyk et al., 1984; Lee et al., 2000). They can be in the form of epilepsia partialis continua (Lee et al., 2000; Parry et al., 2001; Rees et al., 1999) or generalized convulsive status epilepticus (Neufeld et al., 2003). Depending on the disease stage, the EEG can show non-specific findings such as diffuse slowing and frontal rhythmic delta activity in the early stages, disease-typical periodic sharp wave complexes (lateralized or generalized) or PLEDs. Unprovoked seizures have significant consequences on the prognosis of dementia: aggravation in dementia in terms of loss of cognitive abilities, particularly language (Volicer et al., 1995), reduced autonomy, greater risk of injury and a higher mortality rate (Armon et al., 2000; Chandra et al., 1986; Volicer et al., 1995). Seizures may have serious consequences like falls, fractures, intracranial haemorrhages and long-lasting confusion, which is particularly worrisome in dementia. Finally, patients with dementia are very vulnerable to AED (Griffith et al., 2006; Kwan and Brodie, 2001). After a single seizure, AEDs should be only started after the diagnosis has been clearly established and when signs suggesting an anatomical localization are present or when the risk of recurrence is high.
Treatment Epilepsy should be treated with appropriate antiepileptic drugs. In addition, elderly patients who have experienced only one seizure at the time of referral, but who have a high risk of recurrence (for example, patients who have a demonstrated brain lesion related to the seizure) should also receive treatment (Loiseau et al., 1990). However, the antiepileptic drugs chosen should be considered with a global approach. The main goal of management should be the maintenance of autonomy by case by case assessment. A single seizure has a negative effect on the quality of life more than one year after its occurrence even when no etiology has been found (Pedersen, 2002). Elderly people with epilepsy have more trouble sleeping and a higher prevalence of anxiety and depressive disorders when compared to a population of the same age without epilepsy (Haut et al., 2009). However, one study found that seniors with epilepsy did not have poorer health-related quality of life when compared with a population of younger patients with epilepsy (Laccheo et al., 2008). At the present time, we lack reliable
Epilepsy in the Elderly: Diagnostic Approach and Treatment
303
instruments for studying the multiple factors affecting the quality of life in elderly people with epilepsy (Devinsky, 2005). Nevertheless, the first step should always be to carefully analyze the lifestyle of a given patient in order to assess the potential impact of seizures on his or her daily activities (walking, driving). The physician needs to explain the meaning and consequences of the diagnosis of epilepsy and offer appropriate counseling. Thus, a multispecialty, multi-professional approach to care would seem most appropriate (Brodie et al., 2009).
Choice of Antiepileptic Drug A growing body of clinical recommendations based on systematic literature review and expert opinion advocates the use of the newer agents and avoidance of phenobarbital and phenytoin (Pugh et al., 2008). In a practical way, numerous factors should be assessed before prescribing: co-morbidities, pharmacokinetics, poly-therapy and potential drug interactions, side effects, and expected compliance.
Co-Morbidities In the Veterans study which enrolled more than 500 patients (Ramsay et al., 2004), 64% of the patients presented clinically with hypertension, 52% had experienced a stroke, half of them presented with symptomatic cardiac disease, 27% of the patients were diabetic, and 22% had a history of cancer. In addition, 35% of the patients had mild cognitive impairment (patients with Alzheimer disease were excluded from this study). Special consideration should be given to the older population where polypathology is common. Indeed, some AEDs can aggravate preexisting conditions, for example phenytoin can aggravate neuropathy (Yoshikawa et al., 1999) while carbamazepine and phenytoin can lead to cardiac bradyarrhytmia. Weight increase, which is often related to AEDs (pregabalin, valproate) can indirectly decompensate cardiac failure.
Pharmacokinetics Various body organs undergo changes with increasing age that may have effects on the pharmacokinetics of AEDs (Kramer, 2001). Despite the widespread use of AEDs in the elderly, there is limited information on their pharmacokinetics in this age group (Patsalos et al., 2008). A decrease in the absorption area, reduced perfusion, and motility in the digestive tract may have unpredictable effects. Changes in liver function can modify the metabolism of some AEDs and the rate in protein binding. This last characteristic is important to take into account because a low level of albumin due to malnutrition is frequently observed in frail elderly patients. If the AED is highly linked to protein, the risk of toxic side effects is major. However, the most important age-related change in kidney function is a reduction in glomerular filtration and consequently, drugs eliminated predominantly by the kidneys (gabapentin and levetiracetam) should be used cautiously and at a reduced dosage (Perucca,
304
Sophie Dupont, B. De Toffol, Marc Verny et al.
1999). In general, most AEDs should be used at a reduced dosage in order to avoid toxic side effects andtreatment should be individually adapted to each patient.
Poly-medication and Drug-interactions The mean number of co-medications reported in the Veterans study was 6.7 (0-15) and a quarter of the patients were taking 15 or more prescribed drugs (Ramsay et al., 2004). The increase in the mean number of concomitant prescription medications in people with epilepsy ranged from 2.41 for men aged 18-34 years to 7.67 for men aged 85+ years and from 4.04 for women aged 18-34 years to 7.05 for women aged 85+ years (N= 11188), (Gidal et al., 2009). The most commonly used non-AED medications with the potential for adverse drug interactions were reductase inhibitors (statins), calcium channel blockers and selective serotonin reuptake inhibitors (Gidal et al., 2009). Overall, carbamazepine, phenytoin, gabapentin and valproate were the most commonly used AEDs in this study and were prescribed to between 19% and 61% of all patients across the different age group (Gidal et al., 2009). Today, phenytoin remains the most commonly used antiepileptic drug in the USA (Pugh et al., 2008). Some drugs can lower the seizure threshold and increase the risk of seizures (mainly antidepressant and antipsychotic drugs (Spina and Perucca, 2002). However, the most important problem is related to enzyme induction: phenobarbital, phenytoin, and carbamazepine which increases the metabolism of other prescribed drugs leading to an increased risk of toxicity. For example, it is very difficult to manage a co-prescription of warfarin with any of the above-mentioned inducer AEDs but warfarin was prescribed to more than 10% of the patients in the study (Gidal et al., 2009). Among the cardiovascular medication often prescribed, statins are metabolized in the liver and may interact with AEDs (Levy and Collins, 2007). The deleterious effects of older AEDs on bone density are wellknown; they increase the risk of fracture due to osteomalacia (Tallis et al., 2002). Nonspecific side effects of AEDs (mental slowing, sedative effects and confusion) can be unpredictably exaggerated by polymedication. The specific risk of hyponatremia related to oxcarbazepine and carbamazepine must be kept in mind when diuretics are prescribed (Brodie et al., 2009).
Compliance In a recent paper (Ettinger et al., 2009), adherence to AED in elderly patients with epilepsy (N=1278) during a one-year period using the medication possession ration (MPR= sum of days supplied in observation period / days in the observation period) assuming that a MPR < 0.8 defined non-compliance. ; 41% of the 1278 patients were non-compliant. Seizures occurred in 12,1% of non-adherers versus 8,2% of adherers (p= 0,02) and health care costs were increased.
Epilepsy in the Elderly: Diagnostic Approach and Treatment
305
Drug Trials in the Elderly Two multicentre, randomized, double-blind studies comparing lamotrigine and carbamazepine have been published. In the first Brodie et al., (1999), found that lamotrigine was as effective as carbamazepine (standard formulation) but much better tolerated. In the second study (Saetre et al., 2007) with an identical design, lamotrigine was compared to a controlled-release formulation of carbamazepine; the authors found no difference in efficacy or tolerance. In the Veterans Administration study by Rowan et al., (2005), lamotrigine gapapentine and carbamazepine (standard formulation) were compared in a multicentre, randomized, double blind, double dummy, parallel study of 593 elderly subjects with newly diagnosed epilepsy. The primary outcome measure was retention in trial for 12 months. There were no significant differences in the seizure-free rate at 12 months but drop-out rate due to adverse events were lamotrigine: 12,1%, gabapentine: 21,6%, and carbamazepine: 31% (p=0,001). Consequently lamotrigine and gabapentine should be considered as initial medication for older patients with epilepsy. Open studies have been published on numerous new drugs used in mono-therapy: lamotrigine (Giorgi et al., 2001), topiramate (50 mg/day) (Ramsay et al., 2008), levetiracetam (Belcastro et al., 2008)), oxcarbazepine (Kutluay et al., 2003) but no demonstrated differences in efficacy have been found amongst all the available AEDs.
What to Do in Everyday Clinical Practice? The choice of an AED should be individually adapted to each patient according to the physical status of the patient, co-morbidity, potential drug interactions and expected adherence (which mainly depends on the patient‘s cognitive status and family support). The rule should be ―start low and go slow‖ (Brodie et al., 2009) using a mono-therapy. High level clinical evidence is lacking but the use of lamotrigine as first-line treatment is supported by a controlled study. The daily maintenance dose of lamotrigine is 100mg/day (50 mg twice daily). Potential side-effects during the titration period are skin rash and unpredictable sedation. Expected side-effects when the maintenance dose has been attained are headache and insomnia. Levetiracetam also has a good profile: fast titration, no drug interactions and good tolerance). The daily maintenance dose is 1000mg/day (500mg twice daily). Sedation as well as behavioral problems can occur and since the drug is totally excreted by the kidneys, its use requires careful assessment of renal function If a first drug is poorly tolerated, another should be quickly substituted. Treatment is usually for an indefinite period. In all of the cases, particular attention should be paid to side effects and general tolerance needs to be regularly assessed.
Conclusion Despite their high prevalence, epileptic seizures are often overlooked or misdiagnosed in elderly people. Recognizing and correctly diagnosing seizures in this age-group is sometimes a challenge. Aspects that are particularly relevant to the elderly population include: being
306
Sophie Dupont, B. De Toffol, Marc Verny et al.
aware of the usual and unusual clinical presentations of seizures in this age-group, rapidly considering epilepsy when elderly people are referred to emergency departments or geriatricians for confusion, falls, behavioral or psychiatric disorders and that obvious differential diagnoses such as metabolic or toxic disturbances, orthostatic hypotension or syncope also have to be eliminated. In addition, a multidisciplinary approach should be encouraged in order to improve access to useful diagnostic tools such as EEG or video-EEG monitoring. The development of validated diagnostic tools specifically designed for this particular population should be encouraged. AD patients have an increased risk for epilepsy and when both disorders are present, they constitute a complex association with a potentially major psychosocial impact. AEDs should only be started after a diagnosis is clearly established. Newer AEDs seem interesting when compared to the first generation. Even if the newer AEDs offer significant advantages over older medications, clinical trials evaluating their use in the elderly and dementia are needed.
References Proposal for revised classification of epilepsies and epileptic syndromes. Commission on Classification and Terminology of the International League Against Epilepsy (1989). Epilepsia, 30: 389-99. Abubakr A, Wambacq I. (2005) Seizures in the elderly: Video/EEG monitoring analysis. Epilepsy Behav, 7: 447-50. Amatniek JC, Hauser WA, DelCastillo-Castaneda C, Jacobs DM, Marder K, Bell K, et al. (2006) Incidence and predictors of seizures in patients with Alzheimer's disease. Epilepsia, 47: 867-72. Ancoli-Israel S, Ayalon L, Salzman C.(2008) Sleep in the elderly: normal variations and common sleep disorders. Harv. Rev. Psychiatry, 16: 279-86. Archambeaud F, Galinat S, Regouby Y, Magy L, Rebeyrotte I, Vallat JM, et al.(2001) [Hashimoto encephalopathy. Analysis of four case reports]. Rev. Med. Interne, 22: 653-9. Armon C, Peterson GW, Liwnicz BH (2000) Alzheimer's disease underlies some cases of complex partial status epilepticus. J. Clin. Neurophysiol, 17: 511-8. Aronyk K, Petito F, Solomon GE (1984) Partial elementary motor seizures as the first symptom of Creutzfeldt-Jakob disease. Ann. Neurol, 15: 210-1. Babic T, Zurak N (1999) Convulsions induced by donepezil. J Neurol Neurosurg Psychiatry, 66: 410. Belcastro V, Costa C, Galletti F, Autuori A, Pierguidi L, Pisani F, et al (2008) Levetiracetam in newly diagnosed late-onset post-stroke seizures: a prospective observational study. Epilepsy Res, 82: 223-6. Benbadis S, Rielo D (2008) Epileptiform normal variants on EEG. eMedicine Neurology Benbir G, Ince B, Bozluolcay M (2006) The epidemiology of post-stroke epilepsy according to stroke subtypes. Acta Neurol. Scand, 114: 8-12. Bladin CF, Alexandrov AV, Bellavance A, Bornstein N, Chambers B, Cote R, et al (2000) Seizures after stroke: a prospective multicenter study. Arch. Neurol, 57: 1617-22. Brodie MJ, Elder AT, Kwan P (2009) Epilepsy in later life. Lancet Neurol, 8: 1019-30.
Epilepsy in the Elderly: Diagnostic Approach and Treatment
307
Brodie MJ, Overstall PW, Giorgi L (1999) Multicentre, double-blind, randomised comparison between lamotrigine and carbamazepine in elderly patients with newly diagnosed epilepsy. The UK Lamotrigine Elderly Study Group. Epilepsy Res, 37: 81-7. Burn J DM (1997) Epileptic seizures after a first stroke. Br. Med. J, 315: 1582-1587. Cabrejo L, Guyant-Marechal L, Laquerriere A, Vercelletto M, De la Fourniere F, ThomasAnterion C, et al (2006) Phenotype associated with APP duplication in five families. Brain 129: 2966-76. Centorrino F, Goren JL, Hennen J, Salvatore P, Kelleher JP, Baldessarini RJ (2004) Multiple versus single antipsychotic agents for hospitalized psychiatric patients: case-control study of risks versus benefits. Am. J. Psychiatry, 161: 700-6. Chandra V, Bharucha NE, Schoenberg BS (1986) Conditions associated with Alzheimer's disease at death: case-control study. Neurology, 36: 209-11. De Breucker S, Nkodo Mekongo YP, Ibebeke B, Pepersack T (2007) [Falls of older individuals: medical assessment]. Rev. Med. Brux , 28: 177-82. de la Court A, Breteler MM, Meinardi H, Hauser WA, Hofman A (1996) Prevalence of epilepsy in the elderly: the Rotterdam Study. Epilepsia, 37: 141-7. De Reuck J, Nagy E, Van Maele G. Seizures and epilepsy in patients with lacunar strokes. J(2007) Neurol. Sci, 263: 75-8. De Reuck J, Van Maele G (2009) Transient ischemic attacks and inhibitory seizures in elderly patients. Eur. Neurol, 62: 344-8. Devinsky O (2005) Quality of life in the elderly with epilepsy. Epilepsy Behav, 6: 1-3. Dupont S, Verny M, Harston S, Cartz-Piver L, Puisieux F, Benetos A, et al (2009) [Specificity of epileptic seizures in the elderly: A proposed electro-clinical scale]. Rev. Neurol. (Paris), 165: 803-11. Ettinger AB, Manjunath R, Candrilli SD, Davis KL (2009) Prevalence and cost of nonadherence to antiepileptic drugs in elderly patients with epilepsy. Epilepsy Behav, 14: 324-9. Faught E (1999) Epidemiology and drug treatment of epilepsy in elderly people. Drugs Aging, 15: 255-69. Fitzpatrick W, Lowry N (2007) PLEDs: clinical correlates. Can. J. Neurol. Sci, 34: 443-50. Fong TG, Tulebaev SR (2009) Inouye SK. Delirium in elderly adults: diagnosis, prevention and treatment. Nat. Rev. Neurol, 5: 210-20. Forstl H, Burns A, Levy R, Cairns N, Luthert P, Lantos P (1992) Neurologic signs in Alzheimer's disease. Results of a prospective clinical and neuropathologic study. Arch. Neurol, 49: 1038-42. Foster NL, Wilhelmsen K, Sima AA, Jones MZ, D'Amato CJ, Gilman S (1997) Frontotemporal dementia and parkinsonism linked to chromosome 17: a consensus conference. Conference Participants. Ann. Neurol, 41: 706-15. Gibbs E, Fa G (1952) Atlas of Electroencephalography. Cambridge: Addison-Wesley. Gidal BE, French JA, Grossman P, Le Teuff G (2009) Assessment of potential drug interactions in patients with epilepsy: impact of age and sex. Neurology, 72: 419-25. Giorgi L, Gomez G, O'Neill F, Hammer AE, Risner M (2001) The tolerability of lamotrigine in elderly patients with epilepsy. Drugs Aging, 18: 621-30. Granger N, Convers P, Beauchet O, Imler D, Viallon A, Laurent B, et al (2002) [First epileptic seizure in the elderly: electroclinical and etiological data in 341 patients]. Rev. Neurol (Paris), 158: 1088-95.
308
Sophie Dupont, B. De Toffol, Marc Verny et al.
Griffith HR, Martin RC, Bambara JK, Marson DC, Faught E (2006) Older adults with epilepsy demonstrate cognitive impairments compared with patients with amnestic mild cognitive impairment. Epilepsy Behav, 8: 161-8. Hauser WA (1992) Seizure disorders: the changes with age. Epilepsia, 33 Suppl 4: S6-14. Hauser WA (1997) Epidemiology of seizures and epilepsy in the elderly. In: Rowan AJ and Ramsay RE, editors. Boston : Butterworth-Heinemann, 7-18. Hauser WA, Annegers JF, Kurland LT (1993) Incidence of epilepsy and unprovoked seizures in Rochester, Minnesota: 1935-1984. Epilepsia, 34: 453-68. Hauser WA, Annegers JF, Rocca WA (1996) Descriptive epidemiology of epilepsy: contributions of population-based studies from Rochester, Minnesota. Mayo Clin. Proc, 71: 576-86. Hauser WA, Kurland LT (1935) The epidemiology of epilepsy in Rochester, Minnesota, 1935 through 1967. Epilepsia, 16: 1-66. Hauser WA, Morris ML, Heston LL, Anderson VE (1986) Seizures and myoclonus in patients with Alzheimer's disease. Neurology, 36: 1226-30. Haut SR, Katz M, Masur J, Lipton RB (2009) Seizures in the elderly: impact on mental status, mood, and sleep. Epilepsy Behav, 14: 540-4. Hesdorffer DC, Hauser WA, Annegers JF, Kokmen E, Rocca WA (1996) Dementia and adult-onset unprovoked seizures. Neurology, 46: 727-30. Hommet C, Mondon K, Camus V, De Toffol B, Constans T (2008)Epilepsy and dementia in the elderly. Dement. Geriatr. Cogn. Disord, 25: 293-300. Inouye SK (1998) Delirium in hospitalized older patients: recognition and risk factors. J Geriatr Psychiatry Neurol, 11: 118-25; discussion 157-8. Jallon P, Loiseau P, Loiseau J (2001)Newly diagnosed unprovoked epileptic seizures: presentation at diagnosis in CAROLE study. Coordination Active du Reseau Observatoire Longitudinal de l' Epilepsie. Epilepsia, 42: 464-75. Kalpouzos G, Eustache F, Desgranges B (2008) [Cognitive reserve and neural networks in normal aging and Alzheimer's disease]. Psychol. Neuropsychiatr. Vieil, 6: 97-105. Kramer G (2001) Epilepsy in the elderly: some clinical and pharmacotherapeutic aspects. Epilepsia, 42 Suppl 3: 55-9. Kutluay E, McCague K, D'Souza J, Beydoun A (2003) Safety and tolerability of oxcarbazepine in elderly patients with epilepsy. Epilepsy Behav, 4: 175-80. Kwan P, Brodie MJ (2001) Neuropsychological effects of epilepsy and antiepileptic drugs. Lancet, 357: 216-22. Laccheo I, Ablah E, Heinrichs R, Sadler T, Baade L, Liow K (2008) Assessment of quality of life among the elderly with epilepsy. Epilepsy Behav, 12: 257-61. Lamy C, Domigo V, Semah F, Arquizan C, Trystram D, Coste J, et al (2003) Early and late seizures after cryptogenic ischemic stroke in young adults. Neurology, 60: 400-4. Lancman ME, O'Donovan C, Dinner D, Coelho M, Luders HO (1996) Usefulness of prolonged video-EEG monitoring in the elderly. J. Neurol. Sci, 142: 54-8. Lee K, Haight E, Olejniczak P (2000) Epilepsia partialis continua in Creutzfeldt-Jakob disease. Acta Neurol. Scand, 102: 398-402. Levy RH, Collins C (2007) Risk and predictability of drug interactions in the elderly. Int. Rev. Neurobiol, 81: 235-51. Lobo A, Launer LJ, Fratiglioni L, Andersen K, Di Carlo A, Breteler MM, et al (2000) Prevalence of dementia and major subtypes in Europe: A collaborative study of
Epilepsy in the Elderly: Diagnostic Approach and Treatment
309
population-based cohorts. Neurologic Diseases in the Elderly Research Group. Neurology, 54: S4-9. Loiseau J, Loiseau P, Duche B, Guyot M, Dartigues JF, Aublet B (1990) A survey of epileptic disorders in southwest France: seizures in elderly patients. Ann. Neurol, 27: 232-7. Lozsadi DA, Larner AJ (2006) Prevalence and causes of seizures at the time of diagnosis of probable Alzheimer's disease. Dement. Geriatr. Cogn. Disord, 22: 121-4. Luhdorf K, Jensen LK, Plesner AM (1986a) Epilepsy in the elderly: prognosis. Acta Neurol. Scand, 74: 409-15. Luhdorf K, Jensen LK, Plesner AM (1986b) Etiology of seizures in the elderly. Epilepsia, 27: 458-63. Martin J, Shochat T, Ancoli-Israel S (2000)Assessment and treatment of sleep disturbances in older adults. Clin. Psychol. Rev, 20: 783-805. McAreavey MJ, Ballinger BR, Fenton GW (1992) Epileptic seizures in elderly patients with dementia. Epilepsia, 33: 657-60. McBride AE, Shih TT, Hirsch LJ (2002) Video-EEG monitoring in the elderly: a review of 94 patients. Epilepsia, 43: 165-9. Mendez M, Lim G (2003) Seizures in elderly patients with dementia: epidemiology and management. Drugs Aging, 20: 791-803. Mendez MF, Catanzaro P, Doss RC, R AR, Frey WH (1994) 2nd. Seizures in Alzheimer's disease: clinicopathologic study. J. Geriatr Psychiatry Neurol 1994; 7: 230-3. Mendu ML, McAvay G, Lampert R, Stoehr J, Tinetti ME (2009) Yield of diagnostic tests in evaluating syncopal episodes in older patients. Arch. Intern. Med, 169: 1299-305. Moorhouse P, Rockwood K (2008) Vascular cognitive impairment: current concepts and clinical developments. Lancet Neurol, 7: 246-55. Morley JE (2007) Falls--where do we stand? Mo. Med, 104: 63-7. Neary D, Snowden JS, Gustafson L, Passant U, Stuss D, Black S, et al (1998) Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology, 51: 1546-54. Neufeld MY, Talianski-Aronov A, Soffer D, Korczyn AD (2003) Generalized convulsive status epilepticus in Creutzfeldt-Jakob disease. Seizure, 12: 403-5. O'Brien JT, Erkinjuntti T, Reisberg B, Roman G, Sawada T, Pantoni L, et al (2003) Vascular cognitive impairment. Lancet Neurol, 2: 89-98. Palop JJ, Chin J, Roberson ED, Wang J, Thwin MT, Bien-Ly N, et al (2007) Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease. Neuron, 55: 697-711. Parry J, Tuch P, Knezevic W, Fabian V (2001) Creutzfeldt-Jakob syndrome presenting as epilepsia partialis continua. J. Clin. Neurosci, 8: 266-8. Patsalos PN, Berry DJ, Bourgeois BF, Cloyd JC, Glauser TA, Johannessen SI, et al. (2008) Antiepileptic drugs--best practice guidelines for therapeutic drug monitoring: a position paper by the subcommission on therapeutic drug monitoring, ILAE Commission on Therapeutic Strategies. Epilepsia, 49: 1239-76. Pedersen B (2002) Discussion group: seizures dans epilepsy in elderly people. Impact on quality of life. Epilepsia, 43(Suppl8): 9. Perucca E (1999) The clinical pharmacokinetics of the new antiepileptic drugs. Epilepsia, 40 Suppl 9: S7-13.
310
Sophie Dupont, B. De Toffol, Marc Verny et al.
Piecoro LT, Wermeling DP, Schmitt FA, Ashford JW (1998) Seizures in patients receiving concomitant antimuscarinics and acetylcholinesterase inhibitor. Pharmacotherapy, 18: 1129-32. Pugh MJ, Van Cott AC, Cramer JA, Knoefel JE, Amuan ME, Tabares J, et al (2008) Trends in antiepileptic drug prescribing for older patients with new-onset epilepsy: 2000-2004. Neurology, 70: 2171-8. Rabinowicz AL, Starkstein SE, Leiguarda RC, Coleman AE (2000) Transient epileptic amnesia in dementia: a treatable unrecognized cause of episodic amnestic wandering. Alzheimer Dis. Assoc. Disord, 14: 231-3. Ramsay RE, Pryor F (2000) Epilepsy in the elderly. Neurology, 55: S9-14; discussion S54-8. Ramsay RE, Rowan AJ, Pryor FM (2004) Special considerations in treating the elderly patient with epilepsy. Neurology, 62: S24-9. Ramsay RE, Uthman B, Pryor FM, Rowan AJ, Bainbridge J, Spitz M, et al (2008) Topiramate in older patients with partial-onset seizures: a pilot double-blind, dosecomparison study. Epilepsia, 49: 1180-5. Rees JH, Smith SJ, Kullmann DM, Hirsch NP, Howard RS (1999) Creutzfeldt-Jakob disease presenting as complex partial status epilepticus: a report of two cases. J. Neurol. Neurosurg. Psychiatry, 66: 406-7. Reith J, Jorgensen HS, Nakayama H, Raaschou HO, Olsen TS (1997) Seizures in acute stroke: predictors and prognostic significance. The Copenhagen Stroke Study. Stroke 28: 1585-9. Risse SC, Lampe TH, Bird TD, Nochlin D, Sumi SM, Keenan T, et al (1990) Myoclonus, seizures, and paratonia in Alzheimer disease. Alzheimer Dis. Assoc. Disord, 4: 217-25. Romanelli MF, Morris JC, Ashkin K, Coben LA (1990) Advanced Alzheimer's disease is a risk factor for late-onset seizures. Arch. Neurol, 47: 847-50. Rowan AJ, Ramsay RE, Collins JF, Pryor FM, Boardman KD, Uthman BM, et al (2005) New onset geriatric epilepsy. A randomized study of gabapentin, lamotrigine, and carbamazepine. Neurology, 64: 1868-1873. Saetre E, Perucca E, Isojarvi J, Gjerstad L (2007) An international multicenter randomized double-blind controlled trial of lamotrigine and sustained-release carbamazepine in the treatment of newly diagnosed epilepsy in the elderly. Epilepsia, 48: 1292-302. Scarmeas N, Honig LS, Choi H, Cantero J, Brandt J, Blacker D, et al (2009) Seizures in Alzheimer disease: who, when, and how common? Arch. Neurol, 66: 992-7. Shrimpton AE, Schelper RL, Linke RP, Hardy J, Crook R, Dickson DW, et al (2007) A presenilin 1 mutation (L420R) in a family with early onset Alzheimer disease, seizures and cotton wool plaques, but not spastic paraparesis. Neuropathology, 27: 228-32. Singleton AB, Hall R, Ballard CG, Perry RH, Xuereb JH, Rubinsztein DC, et al (2000) Pathology of early-onset Alzheimer's disease cases bearing the Thr113-114ins presenilin1 mutation. Brain, 123 Pt 12: 2467-74. Sirven JI, Ozuna J (2005) Diagnosing epilepsy in older adults: what does it mean for the primary care physician? Geriatrics, 60: 30-5. So EL, Annegers JF, Hauser WA, O'Brien PC, Whisnant JP (1996) Population-based study of seizure disorders after cerebral infarction. Neurology, 46: 350-5. Sperfeld AD, Collatz MB, Baier H, Palmbach M, Storch A, Schwarz J, et al (1999) FTDP-17: an early-onset phenotype with parkinsonism and epileptic seizures caused by a novel mutation. Ann. Neurol, 46: 708-15.
Epilepsy in the Elderly: Diagnostic Approach and Treatment
311
Spina E, Perucca E (2002) Clinical significance of pharmacokinetic interactions between antiepileptic and psychotropic drugs. Epilepsia, 43 Suppl 2: 37-44. Stephen LJ, Brodie MJ (2000) Epilepsy in elderly people. Lancet, 355: 1441-6. Takao M, Ghetti B, Murrell JR, Unverzagt FW, Giaccone G, Tagliavini F, et al (2001) Ectopic white matter neurons, a developmental abnormality that may be caused by the PSEN1 S169L mutation in a case of familial AD with myoclonus and seizures. J. Neuropathol. Exp. Neurol, 60: 1137-52. Tallis R, Boon P, Perucca E, Stephen L (2002) Epilepsy in elderly people: management issues. Epileptic Disord, 4 Suppl 2: S33-9. Thomas P, Beaumanoir A, Genton P, Dolisi C, Chatel M (1992) 'De novo' absence status of late onset: report of 11 cases. Neurology, 42: 104-10. Van Cott AC (2002) Epilepsy and EEG in the elderly. Epilepsia, 43 Suppl 3: 94-102. Van Cott AC (2002) Epilepsy and EEG in th elderly. Epilepsia, 43: 94-. Velez-Pardo C, Arellano JI, Cardona-Gomez P, Jimenez Del Rio M, Lopera F, De Felipe J (2004) CA1 hippocampal neuronal loss in familial Alzheimer's disease presenilin-1 E280A mutation is related to epilepsy. Epilepsia, 45: 751-6. Volicer L, Smith S, Volicer BJ (1995) Effect of seizures on progression of dementia of the Alzheimer type. Dementia, 6: 258-63. Volpe-Gillot L (2007) Troubles cognitifs, démence et épilepsie. Psychol NeuroPsychiatr Vieil 5: S31-40. Waterhouse EJ, DeLorenzo RJ (2001) Status epilepticus in older patients: epidemiology and treatment options. Drugs Aging, 18: 133-42. West RL (1996) An application of prefrontal cortex function theory to cognitive aging. Psychol. Bull, 120: 272-92. Willis MW, Ketter TA, Kimbrell TA, George MS, Herscovitch P, Danielson AL, et al (2002) Age, sex and laterality effects on cerebral glucose metabolism in healthy adults. Psychiatry Res, 114: 23-37. Yanase D, Matsunari I, Yajima K, Chen W, Fujikawa A, Nishimura S, et al (2005) Brain FDG PET study of normal aging in Japanese: effect of atrophy correction. Eur. J. Nucl. Med. Mol. Imaging, 32: 794-805. Yoshikawa H, Abe T, Oda Y (1999) Extremely acute phenytoin-induced peripheral neuropathy. Epilepsia, 40: 528-39
In: Society, Behaviour and Epilepsy Editors: Jaya Pinikahana and Christine Walker
ISBN 978-1-61761-001-1 © 2011 Nova Science Publishers, Inc.
Chapter XVII
Use of Complementary and Alternative Medicine for Treatment of Epilepsy Reyna M. Durón 1 and Kenton R. Holden 2
1. Centro Médico Lucas, Tegucigalpa, Honduras, Central America, Professional Advisory Board, Epilepsy Foundation of Greater Los Angeles 2. Departments of Neurosciences (Neurology) and Pediatrics, Medical University of South Carolina (MUSC), Charleston, SC, USA, and Greenwood Genetic Center (GGC), Greenwood, SC, USA
Abstract Throughout the world, many people use complementary and alternative medicine (CAM) to treat epilepsy. One common CAM used is herbal medicine. Although many plant ingredients are used in modern medications and some appear to have anticonvulsant properties, there are no evidence-based clinical studies that any control epileptic seizures. Difficulties with plant studies arise because concentrations of active principles can vary according to growing conditions. Some are also known to act on the cytochrome p450 system to alter plasma anti-epileptic drug (AED) levels, possibly detrimentally. Literature on other CAMs used in epilepsy is readily available. Acupuncture studies in animals reveal antiepileptic effects and are likely secondary to altering neurotransmission. Prayer, music, and relaxation techniques are also frequently used CAMs. Vitamins and minerals can help prevent some secondary effects of AEDs. Ketogenic and Atkins diets have been found to be useful evidence-based CAM treatments in refractory epilepsies of children and adults. Surveys from Asia, Europe, and the United States have shown that 35 to 72% Correspondence: Kenton R. Holden, M.D., Professor, Departments of Neurosciences (Neurology) and Pediatrics, Medical University of South Carolina (MUSC), Charleston, SC, USA and Senior Clinical Research Neurologist, Greenwood Genetic Center (GGC), Greenwood, SC, USA. E-mail:
[email protected] or
[email protected].
314
Reyna M. Durón and Kenton R. Holden
of patients with severe or refractory neurological disorders use CAM, although many do not report it to their physicians. This percentage is similar for patients with epilepsy, who commonly switch to CAM or combine CAM with prescribed medications. The chance that CAM will be used for an illness appears related to experience with CAM use in the past and a belief in the safety of CAM use. Patients with advanced education degrees beyond upper school appear to have a higher prevalence of CAM use. Commonly patients think that CAMs are safer, more ―natural‖, and lack secondary adverse effects. However, most CAM use is likely precipitated by dissatisfaction with failed evidence-based medical treatments, lack of access to or unavailability of AEDs, inadequate education about epilepsy, insufficient resources, and cultural beliefs. Cultures which believe in diseases caused by ―the supernatural‖ use traditional medicine/CAM as initial therapy rather than of modern medical therapies. CAM use to treat epilepsy has five possible outcomes to the patient. First, their effect is neutral or not harmful and/or they do not interact with an AED or other modern epilepsy treatments. Second, their effect is detrimental to the patient because of direct effects or undesired interactions. Third, they are not effective as an AED, but they do promote general health. Fourth, their effect is unknown, and, therefore, most likely risky. Fifth, they are effective as an AED. CAM use in epilepsy patients often is related to non-adherence to evidencebased AED treatment. Because of the wide range of CAM effects, patients and medical providers need to discuss openly the use of CAM in the treatment of epilepsy. A comprehensive epilepsy education program is needed initially to change non-adherent behaviors and to close the treatment gap for epilepsy. This must go hand-in-hand with improved access to resources and treatment. At the same time, clinical translational research needs to be promoted to determine newer specific and adjuvant therapies for epilepsy, some of which may prove to be CAMs currently in use.
Introduction Many people over the world use complementary and alternative medicine (CAM) to treat acute and chronic illnesses. Since neurological diseases are common (epilepsy, stroke, head trauma, developmental, etc.) and many times do not respond to conventional therapy, CAMs are commonly used. Epilepsy is no exception. Surveys from Asia, Europe, and the United States have shown that 35 to 72% of patients with severe or refractory neurological disorders use CAM, although many do not report it to their physicians. [Barnes et al, 2004 This percentage is similar for patients with epilepsy, who commonly switch to CAM or combine CAM with prescribed medications. [Durón et al, 2009 Traditions, beliefs, and psychosocial factors contribute to treatment practices of epilepsy. These factors appear to differ between developed and developing nations. Even when people migrate from underdeveloped to developed countries, they tend to retain cultural beliefs and treatment practices about epilepsy similar to those in their home countries. Individuals who believe in non-scientific causes of epilepsy tend to initially use complementary and alternative medical therapies. Sometimes, this can lead to risks to health and to diminished quality of life. Epilepsy is a common worldwide health problem; however the etiological causes can differ between developed and developing nations. Recent reports conclude that undeveloped regions, such as parts of Latin America, Asia, and Africa, have higher epilepsy prevalence rates as a result of "preventable" epilepsies.[Medina et al, 2005; Bergen, 1998 Studies in countries like Honduras, Central America also reflect the impact of patient and community perceptions about epilepsy. When 2,221 persons from the Honduran Miskito tribe were
Use of Complementary and Alternative Medicine for Treatment of Epilepsy
315
evaluated during a population-based epilepsy prevalence study and compared to hospital and governmental clinic records, it was found that the epilepsy prevalence was much lower than expected [Varela et al, 2002. It was also observed that there was a strong tendency to explain epilepsy using magical and religious terms and to also use traditional treatments. This study serves as an example of how carefully data needs to be obtained and results reported in epidemiological studies, particularly in certain populations. The social interaction of epilepsy patients with their community and the stigma associated with epilepsy in their community may play a major role in the outcomes of any specific reports on the use of modern medications or CAMs for epilepsy. Additional anthropological studies on epilepsy in different parts of the world have reported that people with epilepsy are frequently believed to be unable to carry on a normal profession or to be independent in everyday tasks [Devinski and Cramer, 1993; Dodrill, 1993. Psychosocial problems stemming from the epilepsies vary among countries and ethnic groups [Lai and Lai, 1991; Pal et al, 2008; Collins, 1994; Elferink, 1999; Durón et al, 2001. Earlier literature from African countries, for example, reported that epilepsy has frequently been treated as an abomination, and there is evidence that in many areas it continues to be abhorred and highly stigmatized [Jilek-Aall et al, 1997; Osuntokun, 1977. Belief remains strong in many regions of the world that only traditional healers are capable of divining the causes and treating the condition. Literature indicates that in rural areas, relatives and family members sometimes accept seizure disorders as a misfortune and do not accept modern medical attention. Use of herbs and non-pharmacological CAMs have been reported by patients everywhere. Since CAM use is common in epilepsy patients, doctors and other allied health personnel should make an effort to learn about it in order to instruct patients, and, if applicable, to rationally use those measures that could be helpful for well being and stress reduction, if not for seizure control. Some complementary treatments are currently helpful in preventing chronic AED adverse effects such as anemia, osteopenia, osteoporosis, and teratogenesis.
Reasons for Cam Use in Epilepsy In developed countries, the search for alternative treatments is initiated primarily due to lack of seizure control from modern AEDs. In addition, CAM use is increased because the most commonly used AEDs can have adverse effects such as allergic reactions, gingival hyperplasia, gastrointestinal disturbances, osteopenia or osteoporosis, bone marrow toxicity, liver toxicity, nephrotoxicity, neurological symptoms (ataxia, dizziness, diplopia, somnolence), cognitive, mood, and behavioral disturbances, endocrine dysfunction, and teratogenicity. Other non-pharmacological evidence-based treatments of epilepsy such as the Ketogenic diet, vagal nerve stimulator, and epilepsy surgery have their own limitations and complications, and many in the world cannot access these evidence-based antiepileptic therapies. Cultures which believe in diseases caused by ―the supernatural‖ inherently feel the need for traditional medicine/CAM rather than modern medicine. Although probably more likely used in developing countries, the chance that CAM will be used for an illness appears related
316
Reyna M. Durón and Kenton R. Holden
to the patient‘s experience with CAM use in the past and a belief in the safety of CAM use. It is of interest that in developed countries, patients with advanced education degrees appear to have a higher prevalence of CAM use. Commonly patients interpret that CAM options are safer because they are ―natural‖. They consider CAMs to lack secondary adverse effects although very few controlled evidence-based studies support this premise. There are some patients who use herbal and dietary supplements for health promotion rather than to specifically treat their epilepsy. Other than that group, however, the ―treatment gap‖ related to evidence-based epilepsy treatment primarily arises from the following factors: dissatisfaction with failed evidence-based medical treatments, lack of access or unavailability of AEDs, inadequate education about epilepsy, insufficient resources, and regional and cultural beliefs. These are also the factors which likely precipitate most CAM use. These reasons can be readily found both in developing and developed countries throughout the world. Table 1. Epilepsy patient and non-patient beliefs about the cause of epilepsy in two cohorts from 3 communities in the rural Department of Olancho, Honduras Responses
Epilepsy patients n=90
Non-patients n=190
Do not know
38
43
Parasites ―bad worm‖ and/or neurocysticercosis
21
13
Heredity
7
19
Cerebral fatigue
4
3
Problems in blood
0
18
Head trauma
4
5
Weakness
2
6
Sorcery, witchcraft, demons, spirits
2
26
Nervousness, anxiety
0
14
Not eating, bad nutrition
2
4
Careless practices*
3
32
Contact with dead bodies
0
4
Drugs, alcohol
0
4
Lack of sexual activity
0
10
Other**
15
59
*like taking a bath immediately after physical activity. **digestive problems, congenital defects, exposure to cold wind, use of forceps during birth, fever, unexpected events/news, lack of menses, problems with husband or family problems, taking a bath during menses, malaria, temperature changes.
Use of Complementary and Alternative Medicine for Treatment of Epilepsy
317
Table 2. Choice of complementary and alternative medicine (CAM) from a national survey of Honduran out-patients with epilepsy related to their community type (urban versus rural) Urban
Rural
Total
No.
%
No.
%
No.
%
Herbs
20
28.6
38
53.5
58
41.1
Potions Amulets Medicine man bath Acupuncture Massage with oils (―sobada‖) Pray to saints Pray to spirits Pray to God Special diet Other
14 1 2 0 1 4 3 42 3 2
20.0 1.4 2.9 0.0 1.4 5.7 4.3 58.6 4.3 2.9
27 1 6 0 4 12 8 38 5 7
38.0 1.4 8.5 0.0 5.6 16.9 11.3 53.5 7.0 9.9
41 2 8 0 5 16 11 80 8 9
29.1 1.4 5.7 0.0 3.5 11.3 7.8 56.7 5.7 6.4
Table 3. Choice of first-aid (multiple responses from an individual were recorded) during an acute epileptic seizure obtained from Miskito tribesmen (n=49) without epilepsy from rural Honduras
Spray water on patient Give Miskito medicine Take patient to clinic Spray aromatic substances Tie or restrain the patient ―Lock‖ the patient Put herbs on eyes (cilantro or garlic) Blowing air Give medicines or pills Give intravenous liquids Watch out for harás Hold the patient Make the patient calm Massage hands with salt Pray Does not know what to do
No. 22 20 11 10 4 3 3 2 2 2 2 1 1 1 1 3
% 45 41 22 20 8 6 6 4 4 4 4 2 2 2 2 6
318
Reyna M. Durón and Kenton R. Holden
Table 4. Adherence history and CAM* use frequency for epilepsy from a national (urban and rural) survey of out-patients with epilepsy throughout all regions of Honduras
Currently taking medicine Had abandoned medicine sometime Gets the medicine all the time Use of CAM* sometime Use of CAM* currently
No. 256 121 223 141 86
% 93.4 44.2 81.4 51.5 31.4
*CAM = complementary and alternative medicine.
There is a diversity of factors influencing CAM use for epilepsy and there is diversity in the specific CAM chosen. Epilepsy patients and normal community members from across the developing country of Honduras, including two tribal groups, were asked what they thought caused epilepsy [Durón et al, 2001, 2009; Varela et al, 2002. Multiple responses from an individual were accepted. Their responses, found in Table 1 and Table 2, indicate their beliefs about epilepsy. These beliefs may explain, in part, the stigma involved and may contribute to the treatment gap and CAM use found in these communities. CAM use is even part of first aid for acute epileptic seizures according to a tribe cohort of 49 non-epilepsy Miskito tribesmen from rural Honduras (Table 3). Additional national survey data taken from Honduran epilepsy out-patients show in Table 4 that CAM use from non-adherence to antiepileptic drugs (AEDs) relates not only to sociocultural aspects but to financial hardship and the treatment gap. Table 5 shows reasons for non-adherence to AED in Honduras [Durón et al, 2009. Whether data was collected in rural or urban centers, the reasons for non-adherence to evidence-based AEDs, as well as the reasons for a high use of CAMs, is multifactorial and not easily solved by financial resources alone. Understanding why patients and their relatives chose CAM use as a substitute for epilepsy treatment will help develop educational strategies to overcome non-adherent issues.
Table 5. Reasons listed from a checklist for non-adherence to their antiepileptic drug(s) from a national (urban and rural) survey of out-patients with epilepsy throughout all regions of Honduras No.
%
Drug not available at hospital
25
20.7
Drug not available at health center
25
20.7
No money to pay for drug
20
16.5
Thought drug didn't work
16
13.2
Forgot to take drug
16
13.2
Did not want to buy drug
15
12.4
Feared reaction to drug
14
11.6
Use of Complementary and Alternative Medicine for Treatment of Epilepsy Table 5. (Continued) No. 10
8.3
No transportation to get drug
9
7.4
No symptoms
8
6.6
Couldn't find a place selling drug
8
6.6
No time to get drug
7
5.8
4
3.4
―Other‖ *
%
Did not want to take drug
*
319
No prescription; drug expired.
CAMS and Evidence Herbal Medicines One of the most common CAMs is herbal medicine. Although many plants have contributed ingredients to modern medications, there is no strong consensus of clinical studies that support their use to control epileptic seizures. A recent Cochrane review analyzed 5 epilepsy herbal treatment trials for epilepsy. Although the methodology was not ideal a few studies showed results which seemed to exhibit some benefit by Far Eastern herbal remedies. Still, current evidence was insufficient to support its use to treat epilepsy [Li et al, 2009. However, some appeared to have anticonvulsant properties in experimental models [Wong, 2010. Animal studies reported from around the world have exhibited in vitro anticonvulsant effects of plants like Capparis deciduas, Solanum nigrum, Croton zambesicus, Nylandtia spinosa L. Dumont, Ficus platyphylla, nutmeg oil of Myristica fragrans, Carissa edulis, Rosa damascene, American skullcap (Scutellaria lateriflora L.), Petiveria alliacea L., Acanthus montanus, Alchornea laxiflora, Hyptis spicigera, Microglossa pyrifolia, Piliostigma reticulatum, Voacanga Africana, and others [Bum et al, 2009. Other reports show anxiolytic and anticonvulsant effects on mice of flavonoids, linalool, and alpha-tocopherol that are present in the extract of leaves of Cissus sicyoides L [de Almeida et al, 2009 . Research has also suggested that the anticonvulsant properties shown by L. alba might be correlated to the presence of a complex of non-volatile substances (phenylpropanoids, flavonoids and/or inositols), and also to the volatile terpenoids (betamyrcene, citral, limonene and carvone), which have been previously validated as anticonvulsants [Neto et al, 2009. Animal models have shown the anticonvulsant properties of Bacopa monnieri extracts and Ficus religios, supporting that 5-HT(2C) receptors are novel targets for developing anti-convulsant drugs [Singh and Goeal, 2009. The Q'eqchi' Maya health system in Central America and Mexico uses a large selection of plants to treat neurological disorders, including epilepsy and anxiety disorders. Canadian researchers have reported a study that evaluated ethanol extracts of 34 plants that were tested in vitro [Awad et al, 2009]. Ten plants showed greater than 50% GABA-T inhibition at 1mg/ml, while 23 showed greater than 50% binding to the GABA(A)-BZD receptor at 250
320
Reyna M. Durón and Kenton R. Holden
microg/ml. Piperaceae, Adiantaceae and Acanthaceae families were highly represented and active in both assays. This suggested a positive correlation between GABA-T inhibition and relative frequency of use for epilepsy [Awad et al, 2009. Similar findings regarding potential antiseizure effects have been reported in a study on the effect of hydro-methanolic percolated extract of Matricaria recutita L. on seizures induced by picrotoxin in male mice [Grundman et al, 2008; Heidari et al, 2009. Several other plants also appear to have anticonvulsant and antianxiety effects due to enhanced GABA effect. [Awad et al, 2009 Resveratrol (Res) is a phytoalexin produced naturally by several plants that has been reported to offer neuroprotection, anti-inflammatory, and anti-cancer effects. A study reported that it showed an anti-epileptic effect against rat kainate-induced temporal lobe epilepsy (TLE). It showed protection of neurons against kainate-induced neuronal cell death in CA1 and CA3a regions and depressed mossy fiber sprouting, which are characteristic both in TLE patients and animal models. Western blot revealed that the expression level of kainate receptors (KARs) in the hippocampus was reduced in Res-administrated rats compared to that in the epileptic group.. These results suggest that plant phytoalexin is a potential anti-epilepsy agent with anti-epileptogenesis properties [Wu et al, 2009. Even though promising results have been shown in pharmacologic and animal studies, difficulties which have been encountered in studies of using herbal medicines for patients with epilepsy include: 1) some herbs are rare or an endangered species, 2) herbs used today may not even correspond to the plants originally described in the old literature, 3) preparations may be from herbs that went through different breeding procedures over several centuries or had different environmental/growing conditions, 4) developing a therapeutic remedy from herbal origins is a complex process that includes standardization of the herbal extract, providing evidence of pharmacological activity, and providing evidence of safety, 5) knowing pharmacokinetic aspects of absorption, knowing the process of the biotransformation of the extract in the body, metabolism, and excretion, 6) the metabolism and pharmacokinetic behavior of active constituents may differ from species to species, and 7) countries define herbal medicines differently and have adopted various approaches to licensing, dispensing, manufacturing, and trading these products. Some plant products have been shown to act on the cytochrome p450 system to alter plasma anti-epileptic drug (AED) levels in epilepsy patients and increase the risk of seizures through direct (pre-convulsant or altered AED metabolic properties) or indirect (contamination with heavy metals or other toxic substances) mechanisms. Table 6 summarizes these and other effects of herbal compounds as reported in the current medical literature [Samuels et al, 2008; Tyai and Delanty, 2009; NLM, 2010a, 2010b. In a recent reported US study of herb and dietary supplement use in patients with epilepsy, approximately one-third of patients used products that had the potential to increase seizures or interact with normal drug metabolism. [Kaiboriboon et al, 2009. The effectiveness and safety of herbal medications for the treatment of epilepsy remains unanswered definitively, especially when used in combination with AEDs. These issues remain in need of much larger, higher quality randomized clinical trials than have been published to date. At this point in time, the known adverse effects and central nervous system drug interactions with herbs should be studied by physicians and allied health personnel and discussed with patients (Table 6). Some specific plants have strong (grade A), good (grade B) or unclear (grade C) scientific evidence of their usefulness. Individual consideration should be carefully evaluated
Use of Complementary and Alternative Medicine for Treatment of Epilepsy
321
when allowing herbs (chamomile, valerian, passiflora) to treat anxiety or insomnia in epilepsy patients, since they could have enhanced sedation effects. In addition, antidepressant drugs are commonly used in epilepsy patients, and their interactions with herbs also need be considered. It is not unusual for patients who use polypharmacy of any type to have unexpected or unexplained adverse side effects, whereas if with the same medications were used alone, the effects would be beneficial. Table 6. A compendium of possible side effects and interactions of commonly used complementary and alternative medicine (CAM) with antiepileptic drugs as well as with other psychopharmacologic medications/compounds Common name Animal or vegetable oils Chamomile
Eucalyptus oil
Scientific name
Common secondary effects
Interactions
None
Interference with intestinal absorption of drugs.
Matricaria recutita, Chamomilla recutita
Sedation can occur.
E. Fructicetorum, Eucalyptus globulus and other species
Gastrointestinal upset, dizziness, muscle weakness, constricted pupils, difficulty breathing, cough, cyanosis, delirium, or convulsions. Less commonly, drowsiness, hyperactivity, difficulty walking, slurred speech, and headache.
Sedation enhanced when combined with AEDs that cause drowsiness (benzodiazepines, barbiturates). May interfere with the cytochrome P450 liver enzyme system, serum levels of AEDs may be increased, with potential increased effects. Increased drowsiness when taken with benzodiazepines, barbiturates, narcotics, some antidepressants, or alcohol. Interference with the cytochrome P450 enzyme system; serum levels of some drugs like barbiturates could be decreased.
322
Reyna M. Durón and Kenton R. Holden
Table 6. A compendium of possible side effects and interactions of commonly used complementary and alternative medicine (CAM) with antiepileptic drugs as well as with other psychopharmacologic medications/compounds (Continued) Common name
Scientific name
Common secondary effects
Interactions
Ephedra
Ephedra sínica, ma huang
Abdominal discomforts, anxiety, dizziness, headache, tremor, insomnia, dry mouth, delirium, fainting, irritability, euphoria, hallucinations, seizures, stroke, hypokalemia, hyperreflexia, weakness, muscle damage, depression, mania, suicidal ideas, Parkinson's disease-like symptoms, kidney stones, hypoglycemia, cardiac arrhythmia, high blood pressure, heart ischemia, myopathy, and cardiac arrest.
Severe cardiovascular and systemic reactions if combined with stimulants, MAOI antidepressants, alkaloids, anesthetic drugs, or antipsychotic drugs. Other antidepressants and medications for psychiatric disorders (phenothiazines, tricyclics, SSRIs) may reduce the effects of ephedra causing low blood pressure and tachycardia. Combination with caffeine may be fatal.
Echinacea
Echinacea angustifolia DC, Echinacea pallida, Echinacea purpurea
Few side effects reported. Complaints include stomach discomfort, sore throat, rash, drowsiness, headache, dizziness, liver dysfunction, thrombotic thrombocytopenic purpura, leukopenia, and muscle aches.
May affect liver metabolism of some drugs including an AED like valproate.
Seizures could occur in individuals with previous seizure disorder, or in individuals receiving antypsychotics or anesthetics. Some report occasional headache, abdominal pain, nausea, and loose stools.
Increased risk of seizures when combined with chlorpromazine, thioridazine, trifluoperazine, fluphenazine, or general anesthesia. Anti-seizure medications may require adjustment because this herb increases risk of seizures. Possible additive effects may occur with anticoagulants, antidepressants, CNS stimulants, and drugs metabolized by the liver.
Few and mild adverse effects like headache, nausea, intestinal complaints, bleeding, and rarely, hypoglycemia, and hypotension. Eating the seeds is potentially deadly, due to risk of tonicclonic seizures and loss of consciousness.
Potential reduction of anti-seizure properties of sodium valproate or carbamazepine. This could be due to altered liver metabolism. Enhanced effects of MAOI drugs, SSRIs, anticoagulants, antiplatelet/aggregation drugs, nonsteroidal anti-inflammatory drugs.
Evening primrose oil
Ginkgo
Ginkgo biloba L.
Use of Complementary and Alternative Medicine for Treatment of Epilepsy
323
Table 6. (Continued) Common name Ginseng
Scientific name
Common secondary effects
Interactions
American ginseng, Asian ginseng, Panax ginseng and other
Seizures have occurred after high consumption of energy drinks containing caffeine, guarana, and herbs, including ginseng. Headache, tremors, mania, or insomnia may occur if combined with MAOIs antidepressants. Potential effect on drug metabolism, by interference with the cytochrome P450 enzyme system, serum levels of certain drugs like AEDs could increase. Ginseng may interact with sedating drugs (like several AEDs).
Kava
Piper methysticum G. Forst
Passiflora, Passion flower
Passiflora incarnata L.
Long-term use may be associated with skin rash, diarrhea, sore throat, loss of appetite, excitability, blood hypertension, hypoglycemia, bleeding, anxiety, depression, or insomnia. Other side effects include headache, dizziness, chest pain, difficult menstruation, breast tenderness, vaginal bleeding after menopause (estrogen-like effects), heartburn, tachycardia, nausea, vomiting, or manic episodes in people with bipolar disorder. Liver toxicity including liver failure. Other serious side effects reported include: skin disorders, blood abnormalities, apathy, kidney damage, seizures, psychotic syndromes, pulmonary hypertension, high blood pressure, meningismus, and kidney toxicity. Mild side effects may include gastrointestinal upset or allergic rash. There are reports of abnormal muscle movements after short-term use, with rigidity, twisting, torticollis, and oculogyric crisis. Tachycardia, nausea, vomiting, drowsiness, sedation, mental slowing. Potential risk of bleeding and alteration of blood tests that measure blood clotting.
Potential increased risk of liver damage if taken with drugs that may affect the liver (such as the AED valproate). AEDs metabolized in kidneys should be used cautiously. There is potential increase in the effects of alcohol and drugs that cause sedation and interference with the cytochrome P450 system, which could increase serum levels of some AEDs.
Some alkaloids with MAOI action present in some species of Passiflora, could enhance MAOI drugs. Increased sedation or low blood pressure could occur when combined with tricyclic antidepressants. There is interaction with sedative drugs (like benzodiazepines and barbiturates), also with drugs metabolized by the liver.
324
Reyna M. Durón and Kenton R. Holden Table 6. (Continued)
St. John's wort
Hypericum perforatum L.
Infrequent gastrointestinal upset, skin reactions, fatigue, sedation, anxiety, sexual dysfunction, photosensitivity, dizziness, headache, blood hypertension, and dry mouth. Some have reported psychiatric symptoms such as suicidal and homicidal thoughts.
Interference with the cytochrome P450 enzyme system, potential increase in serum levels of drugs like carbamazepine, cyclosporin, midazolam, nifedipine, simvastatin, theophylline, warfarin, or HIV drugs. Combination with antidepressants may lead to increased side effects, including serotonin syndrome and mania.
Valerian
Valeriana officinalis L. and other
Headache, excitability, stomach upset, uneasiness, dizziness, ataxia, hypothermia. Chronic use may cause insomnia. Slight transient reductions in concentration or complicated thinking may occur.
Drowsiness may be worsened when taken with sedating medications (benzodiazepines, barbiturates, and other), as a result of GABA enhancement. Potential liver toxicity could affect several drugs metabolism.
Key: SSRI = selective serotonin reuptake inhibitor; MAOI = monoamine oxidase inhibitor; AED = antiepileptic drug; CNS = central nervous system; GABA = gamma-aminobutyric acid; HIV = human immunodeficiency virus. Samuels et al, 2008; Tyagi and Delanty , 2003; NLM 2010a, 2010b.
Acupuncture Acupuncture is an ancient practice introduced by the Chinese culture. New or modified modalities include electroacupuncture, laser acupuncture, acupressure, and catgut implantation to acupoints. It has become an inexpensive and generally safe procedure. According to a recent review of complementary and alternative medicine use in the US population, an estimated 2.1 million people or 1.1% of the population sought acupuncture care during the past 12 months. Four percent of the US population have used acupuncture at some time in their lives [Barnes et al, 2004 Acupuncture is based on beliefs regarding the regulation of five main elements (fire, earth, metal, water, and wood), as well as yin and yang, Qi, and blood and body fluids. It is thought that stimuli to some meridian points can bring internal homeostasis to the body systems. Some studies in animals and humans have shown that responses can occur both close to the site of application and at a distance, mediated mainly by sensory neurons to many structures within the central nervous system. There are several theories about the suspected inhibitory effect of acupuncture in seizures related to increasing the release of inhibitory neurotransmitters. Although animal studies using acupuncture reveal antiepileptic effects, suggesting that suppression of epileptic discharges is secondary to altering neurotransmission, a recent Cochrane review of 11 published studies concludes that acupuncture has not been proven to be safe or effective in treating people with epilepsy [Ceuk et al, 2009. To date, the evidence in favor of acupuncture is more anecdotal than scientific. Randomized doubleblinded studies are needed. With such widespread use of acupuncture at the present time, it
Use of Complementary and Alternative Medicine for Treatment of Epilepsy
325
should be a priority to adequately study whether or not there is a rational acupuncture protocol for specific ages and specific epilepsy types [Jindal et al, 1997.
Psychological-Behavioral Biofeedback, prayer, yoga, music, and other similar therapies could be considered behavioral treatments for epilepsy. They are low-cost, noninvasive, ambulatory interventions that can be used simultaneously with standard treatments of epilepsy [Ramaratnam et al, 2001. These techniques can enhance body and mind health, while at the same time possibly help decrease brain electrical activity which correlates with seizures. They can also be used in different cultural contexts. Biofeedback relaxation or imagery techniques have been found to be useful for anxiety, stress, headache pain, and hypertension which are common comorbidities in epilepsy patients. However, in recent Cochrane reviews of relaxation therapy, cognitive behavioral therapy, electroencephalographic or galvanic skin response biofeedback, as well as yoga as a treatment for control of epilepsy, used alone or in combination, no impact on seizure control was demonstrated. Although these interventions may reduce anxiety, improve social behavior, and improve compliance, further large welldesigned high quality randomized clinical trails are needed to give these therapies reliable evidence to support them for the treatment of epilepsy [Yardi, 2001; Lundgren et al, 2008.
Vitamins and Other Dietary Supplements Vitamins and minerals can help prevent some secondary effects of AEDs, eg, anemia, osteoporosis, and teratogenesis, and are necessary for good health. However, large doses of vitamins do not improve the symptoms of epilepsy and may even be harmful if given in megadoses. A balanced diet should supply most of the vitamins and minerals a person needs each day. People with epilepsy taking AEDs appear to have an increased need for folic acid, calcium, and vitamin D. Women who may become pregnant and pregnant women with and without epilepsy need sufficient folic acid to help prevent birth defects, especially those related to the brain and spinal cord. The conclusion of a recent meta-analysis [AAN, 2009 was that the risk of spinal cord/brain anomalies in the offspring of women with epilepsy is possibly decreased by folic acid supplementation (two adequately sensitive Class III studies). Therefore, it is recommended that preconceptional folic acid supplementation or fortification in women with epilepsy be considered so as to reduce the risk of brain/spinal cord birth defects, especially meningomyelocele. Although the data are insufficient to show that it is effective in women with epilepsy, there is no evidence of the harm and no reason to suspect that it would not be effective in this group. There is no reason to modify the current folic acid supplementation or fortification recommendation that all women of childbearing potential, with or without epilepsy, receive supplementation or fortification with at least 0.4 mg of folic acid daily prior to conception and during pregnancy. Melatonin, a natural hormone secreted by the brain‘s pineal gland, has been thought to reduce the incidence of epilepsy in children. Although there is no large meta-analysis to
326
Reyna M. Durón and Kenton R. Holden
support the use of melatonin at this time for epilepsy therapy, further randomized control studies need to be done with this compound. Melatonin is of special interest since it plays a role in our normal sleep-awake cycle. Many epilepsy patients have additional seizures when they are sleep-deprived. Melatonin may offer in the future a unique opportunity for its use in a subgroup of epilepsy patients if evidence is forthcoming from future treatment trials to support its use.
Alternative Diets Ketogenic and Atkins diets, as well as modifications of these diets, are useful evidencebased CAM therapies for use in refractory epilepsies of children and adults. The Ketogenic diet was initially used in 1921 as a way to cause diet-induced ketosis to mimic fasting, something known since biblical days as a treatment for epilepsy. Approximately 90% of the calories in the Ketogenic diet are derived from fat intake. Although the diet became less popular with the introduction of effective pharmacotherapy, it still remains an effective evidence-based therapy for seizures refractory to AEDs. The Ketogenic diet reduces seizure frequency by > 50% in 54% of children with intractable epilepsy [Vining et al, 2008; Freeman et al, 2009. Although the diet is most effective in infants and young children, success can be found in all age groups. The anti-convulsant mechanism of action is still not known. However, a recent report on mice of the prevention by the Ketogenic diet of myopathic ultrastructural abnormalities from mitochondrial dysfunction appears to be important news in the quest to find an answer to the exact mechanism of action [AholaErkkilä et al, 2010. The modified Atkins diet [Kossoff et al, 2008 is high in fat and low in carbohydrates (low-carb) and has even been found to be useful for developing countries. This modified diet resembles Dr. Atkins‘ low-carb diet designed for both weight loss and healthy living. The "Modified Atkins‖ diet for seizures can be viewed as a "lighter dose" of the Ketogenic diet. More highly studied in children, this less restrictive diet when compared to the Ketogenic diet reduces childhood seizure frequency by > 50% in 47% of children with intractable epilepsy. Adult studies are currently underway and preliminary reports are positive for its effectiveness for seizure control in this population too. Additional studies are also currently underway for other modified diets e.g., low-glycemic index, etc. to find a more tolerable diet that may be more or at least as effective as the Ketogenic diet.
Miscellaneous Therapies (“Other”) There are other CAMs reported by patients which will not be discussed in detail in this chapter. Although they commonly appear on ―news‖ wires and on various ―web-sites‖, therapies such as magnetotherapy, chiropractic, aromatherapy, homeopathy, desensitization and other condition strategies, focal cooling, etc. have had no rigorous scientific studies which conclude that any of them are beneficial in the control of epilepsy.
Use of Complementary and Alternative Medicine for Treatment of Epilepsy
327
CAM Useage Outcomes Health personnel and patients and/or their relatives need to remember the following about CAM usage outcomes. There are five possible results in the patient from using CAMs to treat epilepsy. First, their effect is neutral or not harmful and/or they do not interact with an AED or other modern epilepsy treatments. Second, their effect is harmful or detrimental to the patient because of primary/secondary effects or undesired interactions. Third, they are not effective as an AED, but they do promote general health. Fourth, their effect is unknown, and, therefore, most likely risky. Fifth, they are effective as an AED.
Conclusion Because of the wide range of CAM effects, patients and medical providers need to discuss openly the use of CAMs in the acute and chronic treatment of epilepsy. Widespread non-adherence to evidence-based epilepsy treatments can be attributed to inadequate education, AED unavailability, insufficient resources, cultural beliefs, and wide use of CAMs. A comprehensive epilepsy education program, along with improved access to evidence-based AEDs, appears to be the initial step to change non-adherent behaviors and to close the epilepsy treatment gap of non-adherence to prescribed evidence-based anti-convulsant medications and other therapies [Meinardi et al, 2001. At the same time, clinical translational research needs to be promoted to determine newer specific and alternative therapies for epilepsy, some of which may prove to be CAMs currently in use at the present time.
References AAN. Report of the Quality Standards Subcommittee and Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and American Epilepsy Society (2009) Practice Parameter update: Management issues for women with epilepsy—focus on pregnancy (an evidence-based review): Vitamin K, folic acid, blood levels, and breastfeeding. Epilepsia. 50(5):1247-55. Ahola-Erkkilä S, Carroll C, Peltola-Mjösund K, Tulkki V, Mattila I, Seppänen-Laakso T, et al.(2010) Ketogenic diet slows down mitochondrial myopathy progression in mice. Human Mol. Genet. Feb. 17, (e-pub ahead of print). de Almeida ER, Rafael KR, Couto GB, Ishigami AB.(2009) Anxiolytic and anticonvulsant effects on mice of flavonoids, linalool, and alpha-tocopherol presents in the extract of leaves of Cissus sicyoides L.(Vitaceae). J. Biomed .Biotechnol;274740. Awad R, Ahmed F, Bourbonnais-Spear N, Mullally M, Ta CA, Tang A, et al. (2009) Ethnopharmacology of Q'eqchi' Maya antiepileptic and anxiolytic plants: effects on the GABAergic system. J. Ethnopharmacol, 125(2):257-64. Barnes PM, Powell-Griner E, JcFann K, Nahin RL.(2004) Complementary and alternative medicine use among adults: United States. Adv. Data;343:1-19. Bergen DC (1998) Preventable neurological diseases worldwide. Neuroepidemiolog, 17(2):67-73.
328
Reyna M. Durón and Kenton R. Holden
Bum EN, Taiwe GS, Nkainsa LA, Moto FC, Seke Etet PF, Hiana IR, et al (2009) Validation of anticonvulsant and sedative activity of six medicinal plants. Epilepsy Behav, 14(3):454-8. Cheuk DKL,Wong V. Acupuncture for epilepsy. Cochrane Database of Systematic Reviews 2008, Issue 4. Art. No.: CD005062. DOI: 10.1002/14651858.CD005062.pub3. Collings JA (1994) International differences in psychosocial well-being: a comparative study of adults with epilepsy in three countries. Seizure, 3:183-190. Devinsky O, Cramer JA (1993) Introduction: Quality of Life in Epilepsy Epilepsia, 34(suppl 4):1-3. Dodrill CB (1993) Historical perspectives and future directions. In: The treatment of epilepsy: principles and practices. Edited by Elaine Wyllie. Philadelphia, Lea and Febiger, 1129-1132. Durón R, Medina MT, Boyd D, Stansbury J.(2001) Antropología de las epilepsias. In: Medina, Chávez, Chinchilla and Gracia Eds. Las Epilepsias en Centroamérica. Scancolor: Tegucigalpa, 229-235. Durón R, Medina MT, Holden K, Ramírez F, et al. (2001) Estudio sobre el cumplimiento del tratamiento por los pacientes epilépticos del Hospital Escuela. Rev. Med. Hond. 69(4) Durón RM, Medina MT, Nicolás O, Varela FE, Ramírez F, Battle SJ, Thompson A, Rodríguez LC, Oseguera C, Aguilar-Estrada RL, Pietsch-Escueta S, Collins JS, Holden KR (2009) Adherence and complementary and alternative medicine use among Honduran people with epilepsy. Epilepsy Behav, 14(4):645-50. Elferink JG (1999) Epilepsy in the ancient cultures of America (I). International Epilepsy News. Netherlands: International Bureau for Epilepsy, 137:5-8. Freeman JM, Vining EP, Kossoff EH, Pyzik PL, Ye X, Goodman SN (2009) A blinded, crossover study of the efficacy of the ketogenic diet. Epilepsia, 50(2):322-5. Grundmann O, Wang J, McGregor GP, Butterweck V (2008) Anxiolytic activity of a phytochemically characterized Passiflora incarnate extract is mediated via the GABAergic system. Planta Med, 74(15):1769-73. Heidari MR, Dadollahi Z, Mehrabani M, Mehrabi H, Pourzadeh-Hosseini M, Behravan E, et al(2009) Study of antiseizure effects of Matricaria recutita extract in mice. Ann. N. Y. Acad. Sci,1171:300-4. Jilek-Aall L, Jilek M, Kaaya J, Mkombachepa L, Hillary K(1997) Psychosocial study of epilepsy in Africa. Soc. Sci. Med, 45(5):783-95. Jindal V, Ge A, Mansky PJ (2008) Safety and efficacy of acupuncture in children: a review of the evidence. J. Pediatr Hematol. Oncol, 30(6):431–42. Kaiboriboon K, Guevara M, Alldredge BK (2009) Understanding herb and dietary supplement use in patients with epilepsy. Epilepsia, 50:1927-32. Kossoff EH, Dorward JL, Molinero MR, Holden KR (2008) The modified Atkins diet: A potential treatment for developing countries. Epilepsia, 49:1646-47. Lai CW, YH Lai (1991) History of epilepsy in chinese traditional medicine. Epilepsia, 32(3):299-302. Li Q, Chen X, He L, Zhou D. Traditional Chinese medicine for epilepsy. Cochrane Database of Systematic Reviews 2009, Issue 3. Art. No.: CD006454. DOI: 10.1002/14651858. CD006454.pub2.
Use of Complementary and Alternative Medicine for Treatment of Epilepsy
329
Lundgren T, Dahl J, Yardi N, Melin L (2008) Acceptance and commitment therapy and yoga for drug-refractory epilepsy: a randomized controlled trial. Epilepsy and Behavior, 13:102–8. Medina MT, Durón RM, Martínez L, Osorio JR, Estrada AL, Zúniga C, Cartagena D, Collins JS, Holden KR (2005) Prevalence, incidence, and etiology of epilepsies in rural Honduras: the Salamá study. Epilepsia 46:124-131. Meinardi H, Scott RA, Reiss, JWAS Sander (2001) ILAE Commission report. The treatment gap in epilepsy: the current situation and ways forward. Epilepsia, 42(1):136-149. Neto AC, Netto JC, Pereira PS, Pereira AM, Taleb-Contini SH, França SC, et al (2009) The role of polar phytocomplexes on anticonvulsant effects of leaf extracts of Lippia alba (Mill.) N.E. Brown chemotypes. J. Pharm. Pharmacol, 61(7):933-9. National Library of Medicine (NLM). MedlinePlus. Drugs and supplements. All drugs and supplements.Accessed 03/10/2010a. Available from: http://www.nlm.nih.gov/ medlineplus/druginfo/herb National Library of Medicine (NLM). Dietary Supplements Labels Database. Accessed 03/10/2010b. Available from: http://dietarysupplements.nlm.nih.gov/dietary/herbIngred. jsp. Osuntokun B (1977) Epilepsy in the African Continent. In: Penry JK Ed. Epilepsy, The Eighth International Symposium, New York: Raven Press;:365-378. Pal SK, Sharma K, Prabhakar S, Pathak A.(2008) Psychosocial, demographic, and treatmentseeking strategic behavior, including faith healing practices, among patients with epilepsy in northwest India. Epilepsy Behav, 13(2):323-32. Ramaratnam S, Baker GA, Goldstein LH. Psychological treatments for epilepsy. Cochrane Database Syst. Rev. 2001;4:CD002029. Samuels N, Finkelstein Y, Singer SR, Oberbaum M.(2008) Herbal medicine and epilepsy: proconvulsive effects and interactions with antiepileptic drugs. Epilepsia, 49(3):373-80. Singh D, Goel RK(2009) Anticonvulsant effect of Ficus religiosa: role of serotonergic pathways. J. Ethnopharmacol, 123(2):330-4. Tyagi A, Delanty N (2003) Herbal remedies, dietary supplements, and seizures. Epilepsia 44(2):228-35. Varela F, Nicolás O, Durón R, Medina MT (2002) Aspectos antropológicos y culturales que inciden en la determinación de la prevalencia de las epilepsias en la etnia miskita de Honduras. Rev. Med. Hond, 70:9-14. Vining EP(2008) Long-term health consequences of epilepsy diet treatments. Epilepsia 49(Suppl 8):27-9. Wong M (2010) Herbs and spices: Unexpected sources of antiepileptogenic drug treatments? Epilepsy Currents, 10:21-23.Wu Z, Xu Q, Zhang L, Kong D, Ma R, Wang L (2009) Protective effect of resveratrol against kainate-induced temporal lobe epilepsy in rats. Neurochem. Res,34 (8):1393-400. Yardi N (2001) Yoga for control of epilepsy. Seizure,10: 7–12
Index A absorption, 303, 320, 321 abuse, xvi, 196, 234, 251, 252, 259, 297 academic performance, 111 accessibility, 131, 167, 169, 276 accommodation, 100, 102, 103, 105 accuracy, 85, 179, 184, 210 acetylcholinesterase, 310 acetylcholinesterase inhibitor, 310 acid, 67, 130, 136, 139, 258, 324, 325, 327 acquaintance, 24 activism, 146 acupuncture, x, 83, 324, 328 ADA Amendments Act, 110 adaptation, xiv, 34, 46, 47, 98, 112, 204, 217, 228, 232, 240, 241, 242, 246, 253 adaptations, 38 adaptive functioning, 235 ADHD, 215, 222, 226 adjustment, 18, 19, 43, 44, 47, 48, 49, 55, 56, 102, 108, 118, 133, 209, 211, 215, 217, 221, 228, 230, 231, 232, 235, 236, 237, 238, 242, 244, 245, 246, 256, 322 administrators, 65, 148 adolescent boys, 124 adolescent development, 201 adolescents, xiii, 35, 112, 124, 134, 177, 183, 184, 186, 187, 191, 193, 196, 197, 199, 202, 203, 205, 216, 217, 221, 222, 223, 224, 225, 227, 232, 237, 241, 242, 243, 244, 245 adult literacy, 87 adulthood, 45, 46, 49, 57, 128, 191, 234, 251, 284 advantages, 146, 155, 290, 306 adverse event, 57, 262, 305 advocacy, 37, 104, 106 aetiology, 47, 112, 241, 290, 293, 301
affective disorder, 47, 127, 223, 278 affective meaning, 23 affirmative action, 103 Africa, 32, 39, 57, 66, 67, 71, 88, 95, 97, 105, 112, 114, 158, 258, 261, 280, 287, 314, 328 African Americans, 31, 77, 266 agencies, 103, 106, 146 aggregation, 322 aggression, 211, 212, 230 AIDS, 24, 25, 26, 27, 66, 67, 68, 69, 90, 144, 160, 205, 280 albumin, 303 alcohol use, 190, 268 alcoholism, 292 algorithm, 298 alienation, 65 alkaloids, 322, 323 allergic reaction, 315 alpha-tocopherol, 319, 327 alternative medicine, x, 30, 161, 172, 174, 313, 314, 317, 318, 321, 322, 324, 327, 328 alternative treatments, 315 ambivalence, 274 amenorrhea, 119 American Psychiatric Association, 156, 253, 254, 259, 277 Americans with Disabilities Act, 100, 102, 103, 104, 107, 109, 110, 113 amnesia, 292, 294, 295, 310 amulet, 171 anemia, 315, 325 anesthetics, 322 anger, 6, 12, 81 angina, 262 anthropologists, 34 anthropology, xvii, 29, 30, 40, 173 antibiotic, 160
332 anti-cancer, 70, 320 anticholinergic, 294 anticonvulsant, 129, 136, 137, 138, 139, 201, 204, 227, 240, 242, 284, 292, 313, 319, 320, 327, 328, 329 anticonvulsant treatment, 227 antidepressant, 247, 250, 266, 271, 282, 304, 321 antidepressant medication, 247, 271 anti-inflammatory drugs, 322 antimicrobial therapy, 205 antipsychotic, 304, 307, 322 antipsychotic drugs, 304, 322 antiretrovirals, 67 antisocial behavior, 191, 211, 218, 243 anxiety, 6, 10, 11, 12, 14, 16, 45, 47, 48, 50, 55, 98, 120, 121, 122, 124, 126, 127, 129, 132, 136, 137, 138, 151, 154, 158, 176, 183, 187, 190, 205, 211, 212, 215, 216, 217, 221, 226, 229, 230, 231, 233, 234, 235, 236, 237, 240, 241, 242, 243, 246, 251, 253, 254, 262, 264, 279, 281, 282, 283, 285, 302, 316, 319, 321, 322, 323, 324, 325 anxiety disorder, 127, 138, 242, 319 aortic stenosis, 294 apathy, 323 appetite, 253, 259, 268, 323 appointments, 192, 193, 199, 203, 265 aptitude, 77 Arab countries, 133 Arab world, 172 arousal, 119, 120, 132 arrest, 322 arrhythmia, 322 artery, 295 arthritis, 262 articulation, 246 Asia, 25, 70, 95, 96, 97, 112, 286, 313, 314 Asian countries, 267 Asian values, 32 assassination, 39 assessment, ix, x, xiii, 5, 16, 30, 35, 39, 40, 44, 56, 57, 71, 76, 77, 87, 88, 94, 95, 106, 109, 110, 145, 174, 180, 181, 182, 183, 184, 185, 196, 198, 200, 204, 207, 208, 211, 220, 222, 223, 228, 244, 251, 255, 258, 269, 270, 271, 274, 282, 294, 302, 305, 307 assessment techniques, 181 assessment tools, 35, 76, 251 assets, 63 asterixis, 294 asthenia, 291, 297
Index asthma, 123, 133, 135, 180, 188, 202, 203, 217, 229, 230, 231, 236, 237, 242, 243, 262, 280 asylum, 148, 149, 156 ataxia, 315, 324 atonic, 6 atrophy, 311 attachment, 262 attitude measurement, 100 attribution, 143, 144 auscultation, 295 authorities, 151, 165, 171 autism, 24, 26, 136, 139, 140 automatisms, 295, 297 autonomy, 53, 186, 191, 237, 238, 302 autopsy, 178, 290, 300 avoidance, viii, 1, 84, 219, 238, 252, 268, 303
B barbiturates, 321, 323, 324 barriers, vii, ix, x, xiii, 32, 33, 61, 93, 94, 95, 97, 103, 104, 106, 107, 124, 153, 183, 184, 189, 191, 192, 193, 194, 196, 197, 198, 219, 257, 258, 265, 267, 268, 274, 276, 277, 282 basic services, 61 Beck Depression Inventory, 268 behavior therapy, 205, 282 behavioral aspects, 202 behavioral assessment, 196 behavioral change, 252 behavioral dimension, 211 behavioral disorders, 298 behavioral problems, ix, 207, 208, 211, 212, 213, 214, 215, 216, 217, 218, 219, 305 behaviors, 34, 76, 85, 105, 108, 181, 183, 184, 190, 191, 196, 197, 198, 199, 201, 202, 203, 209, 210, 211, 215, 217, 219, 242, 252, 254, 262, 268, 271, 273, 274, 277, 314, 327 belief systems, 23, 32, 33, 165, 168, 169 benign, 243, 294, 299 benzodiazepine, 118 bias, 22, 190, 291 bile, 147 binding globulin, 121 bioassay, 180 biofeedback, 325 biological consequences, 276 bioterrorism, 83 bipolar disorder, 250, 253, 287, 323 births, 120
Index bleeding, 128, 322, 323 blood clot, 323 blood plasma, 182 blood pressure, 295, 322, 323 blood transfusion, 83 body fat, 124 body fluid, 324 body image, 124 body weight, 182 bone, 130, 204, 304, 315 bone marrow, 204, 315 bone marrow transplant, 204 bone mass, 130 brain, x, xiv, 2, 24, 37, 74, 86, 89, 110, 118, 134, 136, 137, 138, 141, 145, 147, 153, 154, 156, 157, 168, 213, 227, 233, 241, 243, 250, 259, 261, 262, 290, 291, 292, 299, 300, 302, 325 brain abnormalities, 213 brain activity, 243 brain damage, 227, 233 brain structure, 259 Brazil, 3, 79, 84, 87, 89 breakdown, 33 breast cancer, 84, 90, 91 breastfeeding, 130, 327 breathing, 104, 295, 321 breeding, 320 Britain, 96, 112, 150, 153 brothers, 38, 234 bruit, 295 bubonic plague, 148 Buddhism, 285 budget allocation, 62 building blocks, 209 bullying, 223
C caesarean section, 128 caffeine, 322, 323 calcium, 304, 325 calcium channel blocker, 304 Cambodia, 62, 70 campaigns, 31, 83 cancer, vii, 24, 26, 70, 84, 88, 90, 91, 174, 205, 260, 262, 303, 320 cancer screening, 84, 91 candidates, 74, 226 carbohydrates, 326 cardiac arrest, 322
333
cardiac arrhythmia, 322 cardiovascular disease, 89, 261, 297 cardiovascular function, 294 cardiovascular system, 301 care model, 65, 198, 270, 277 caregivers, ix, 35, 58, 73, 74, 84, 85, 86, 91, 176, 177, 183, 184, 189, 191, 192, 193, 196 carotid sinus, 294, 295 case study, 33, 64 catatonia, 250 caucasians, 77 causal relationship, 280 causality, 210 causation, 147, 151, 157 cell death, 129, 137, 320 cell phones, 37 central nervous system, 188, 208, 212, 224, 231, 320, 324 cerebral cortex, 156 cerebral palsy, 99, 173, 209, 242 cerebrovascular disease, 118, 290, 291 cervical cancer, 88 channel blocker, 304 character traits, 251 child abuse, 234 child bearing, 129 Child Behavior Checklist, 211, 220, 241 childhood, ix, xvi, 31, 65, 79, 123, 133, 182, 199, 200, 201, 202, 203, 204, 207, 208, 210, 215, 217, 218, 220, 221, 222, 223, 224, 225, 226, 227, 228, 230, 231, 242, 246, 262, 326 childhood disorders, 225 Chile, 258, 287 China, vii, 30, 32, 39, 40, 41, 63, 80, 89, 114 Chinese medicine, 30, 169, 328 cholinesterase, 301 cholinesterase inhibitors, 301 Christians, 147 chromatography, 182, 203 chromosome, 301, 307 chronic diseases, xi, xii, 114, 194, 221, 230, 233, 237, 260, 261, 262, 266, 276, 284 chronic illness, xii, xiii, xiv, 23, 24, 26, 27, 31, 32, 38, 44, 54, 109, 112, 176, 180, 193, 204, 207, 213, 217, 218, 227, 228, 229, 230, 232, 236, 238, 239, 246, 260, 269, 278, 289, 314 churches, 285 circadian rhythm, 295 citizenship, xvi, 67, 68, 70 city, 39, 96, 112, 173
334 civil rights, 94, 103, 104 clarity, 249 class, 90, 139, 149, 150, 173, 271 clients, 66, 106 clinical diagnosis, 295, 300 clinical neurophysiology, xii, xv, 145 clinical presentation, 291, 292, 293, 294, 306 clinical psychology, xi, 157, 287 clinical symptoms, 294, 295 clinical trials, xv, 56, 178, 193, 306, 320 closure, 106 clusters, 47 CNS, 118, 136, 208, 209, 210, 213, 214, 229, 322, 324 coercion, 152 cognition, 44, 188, 213, 221, 222, 223, 224, 263 cognitive abilities, 88, 128, 209, 302 cognitive deficit, 215 cognitive deficits, 215 cognitive development, 123 cognitive dysfunction, 79, 247, 294 cognitive function, 79, 128, 189, 213, 214, 215, 221, 256, 263, 284, 298, 300 cognitive impairment, 13, 154, 214, 218, 236, 263, 294, 297, 301, 303, 308, 309 cognitive slowing, 79 cognitive therapy, 283, 284, 286, 287 college students, 114 collusion, 146, 154, 157 colonisation, 156 coma, 292 combination therapy, 74 common symptoms, 10 communalism, 32 communication skills, 76, 216, 239 communication strategies, 269 community, vii, viii, ix, xii, xvi, xvii, 26, 31, 32, 34, 45, 48, 51, 53, 55, 57, 64, 65, 69, 83, 84, 88, 95, 96, 97, 98, 105, 108, 110, 111, 112, 125, 126, 135, 138, 141, 148, 150, 163, 164, 165, 166, 167, 168, 169, 170, 171, 189, 229, 254, 256, 263, 264, 267, 276, 280, 281, 283, 284, 286, 314, 317, 318 community support, 33, 65 comorbidity, x, 135, 154, 266, 278, 280, 282, 286 comparative costs, 286 compensation, 104 competition, 146 complaints, 105, 227, 230, 231, 232, 235, 237, 238, 241, 259, 260, 295, 322
Index complex partial seizure, 6, 7, 8, 13, 47, 95, 117, 139, 221, 225, 232, 243, 245, 291, 300 complexity, ix, x, 73, 75, 228 compliance, 64, 85, 109, 112, 168, 176, 191, 197, 199, 200, 201, 203, 204, 208, 228, 240, 242, 245, 251, 252, 303, 304, 325 complications, 53, 66, 95, 128, 132, 135, 315 composition, 187 compounds, 260, 320, 321, 322 comprehension, 75, 86 computer chips, 181 conceptual model, 245, 251, 262 conceptualization, 34, 103, 259 concordance, 168, 169, 177, 233 conduct disorder, 230 conduction, 294 conference, xiii, 277, 307 confidentiality, 167 configuration, 239 configurations, 239 confinement, 152 conflict, 176, 191, 198, 238, 260 conflict resolution, 238 congenital malformations, 128, 139 connectivity, 53, 139 consciousness, 51, 151, 292, 293, 294, 295, 297, 298, 322 consensus, 138, 307, 309, 319 construct validity, 184 consulting, xiv, 287 consumer choice, 173 consumption, 3, 251, 323 contamination, 320 contingency, 197 contraceptives, 127, 139 control group, 45, 78, 85, 118, 120, 121, 196, 229, 234, 239, 275, 276 controlled studies, 118 cooking, 7, 12 cooling, 326 coordination, 90 COPD, 204 coping strategies, 114, 124, 241, 253, 265, 268 coronary heart disease, 255, 278, 285 correlation, 52, 76, 90, 214, 229, 250, 320 correlations, xv cortex, 139, 156, 311 cosmopolitanism, xvi cost, 24, 30, 39, 57, 59, 60, 62, 63, 65, 67, 68, 69, 79, 97, 102, 113, 148, 163, 167, 169, 170, 182, 183,
Index 185, 199, 201, 205, 265, 274, 277, 286, 295, 307, 325 Costa Rica, 105 cough, 321 coughing, 295 counseling, 32, 85, 106, 138, 193, 268, 274, 279, 303 counter measures, 4, 14 covering, 103 craving, 251 creativity, 38 Creutzfeldt-Jakob disease, 302, 306, 308, 309, 310 criminal tendencies, 158 criticism, 76, 144, 149, 157, 191, 228, 235, 240 critics, 162 Croatia, 11, 154 cross-cultural comparison, 15 CT scan, 302 cues, 210 cultural barriers, 32 cultural beliefs, 4, 30, 314, 316, 327 cultural differences, 54, 76, 200, 267 cultural studies, 33 cultural values, 169 culture, 3, 33, 34, 35, 43, 49, 84, 173, 209, 234, 324 cyanosis, 321 cycles, 117, 119, 120, 131, 273 cyst, 120 cystic fibrosis, 180, 203, 205, 231 cytochrome, 313, 320, 321, 323, 324 cytochrome p450, 313, 320 Czech Republic, 81, 89
D daily living, 51, 235, 300 danger, 11, 23, 151, 157 data collection, 10, 185, 267 data gathering, 9 data set, 19 database, 5 death rate, 158 deaths, 118 deconstruction, 159 deep brain stimulation, 74 defecation, 295 defects, 316, 325 defence, 143, 152, 156, 166 deficit, 211, 215, 223, 224, 293, 297, 298 deinstitutionalization, 267 delinquent behavior, 238
335
delirium, 293, 294, 321, 322 delusions, 294 dementia, x, xv, 148, 157, 289, 290, 291, 293, 294, 298, 300, 301, 302, 306, 307, 308, 309, 310, 311 demographic characteristics, 1, 5, 8 demographic data, 81 dengue, 62, 66, 70 dengue fever, 62 denial, 20, 124, 190, 238, 265 Denmark, 3, 26 Department of Health and Human Services, 33, 41, 76, 89, 90 dependent variable, 22 depressants, 272 depressive symptoms, 58, 231, 242, 251, 253, 254, 256, 260, 262, 264, 265, 268, 269, 270, 271, 272, 275, 276, 278, 281, 283, 284, 285 deprivation, 1, 3, 7, 10, 12, 13, 31, 39, 80 desensitization, 326 destruction, 159, 251 detection, 76, 101, 141, 205, 266, 277, 281 developed countries, x, 30, 66, 67, 97, 116, 314, 315, 316 developed nations, 69 developing brain, 134, 136, 138 developing countries, xv, 30, 59, 60, 61, 63, 64, 65, 66, 67, 68, 69, 70, 71, 96, 97, 116, 258, 261, 286, 315, 326, 328 developing nations, 106, 314 devolution, 249 diabetes, xii, 23, 24, 58, 66, 86, 90, 180, 188, 198, 199, 201, 202, 205, 217, 229, 230, 231, 244, 245, 246, 261, 262, 266, 280, 294 diagnosis, vii, x, xviii, 13, 20, 21, 34, 35, 38, 44, 47, 49, 50, 76, 109, 129, 137, 144, 154, 156, 170, 190, 193, 197, 211, 213, 215, 224, 242, 247, 253, 254, 257, 258, 265, 266, 268, 269, 270, 277, 281, 286, 289, 290, 291, 292, 294, 295, 296, 297, 298, 299, 300, 302, 303, 306, 307, 308, 309 Diagnostic and Statistical Manual of Mental Disorders, 156, 253, 254 diagnostic criteria, 266, 309 diarrhea, 323 diet, x, 4, 7, 12, 74, 88, 147, 315, 317, 325, 326, 327, 328, 329 dieting, 1 differential diagnosis, 47 diffusion, 295 diplopia, 315 direct cost, 178
336 direct costs, 178 direct observation, x, 228, 235, 236 disability, xiv, 31, 40, 60, 93, 94, 98, 100, 101, 102, 103, 104, 105, 106, 107, 109, 112, 113, 114, 143, 146, 154, 167, 172, 173, 204, 219, 225, 226, 248, 258, 260, 261, 279, 280, 285, 286 disadvantages, 146 discharges, 119, 135, 292, 299, 302, 324 disclosure, 83, 100, 101, 106, 108, 113 discomfort, 259, 269, 322 discrimination, viii, 18, 19, 23, 25, 26, 48, 50, 64, 83, 94, 99, 100, 103, 104, 105, 111, 144, 157, 172, 217, 247, 253 disease activity, 239 disease model, 250 disorder, 2, 20, 21, 24, 29, 37, 43, 44, 45, 46, 47, 48, 49, 52, 54, 55, 80, 81, 82, 111, 120, 127, 138, 139, 143, 144, 145, 147, 148, 151, 153, 154, 156, 157, 166, 202, 213, 214, 215, 223, 224, 225, 230, 234, 238, 243, 244, 248, 249, 250, 251, 252, 253, 254, 256,묈257, 258, 261, 262, 263, 266, 281, 282, 286, 287, 295, 297, 322, 323 dissatisfaction, x, 167, 193, 314, 316 dissociation, 90 distress, ix, 22, 35, 48, 52, 53, 121, 135, 143, 144, 187, 233, 235, 259, 262, 266 disturbances, xv, 119, 139, 268, 289, 292, 294, 306, 309, 315 divergence, 153 diversity, 318 dizziness, 291, 295, 300, 315, 321, 322, 323, 324 doctors, 36, 65, 108, 146, 149, 155, 158, 161, 166, 172, 277, 315 dominance, 146, 148, 156, 170 donations, 61, 67 donors, 64 dopamine, 258 dosage, 52, 178, 198, 202, 303 dosing, 85, 91, 176, 179, 180, 181, 182, 188, 193, 195, 196, 197, 198, 205 drainage, 150 drawing, 239 drug interaction, 128, 303, 304, 305, 307, 308, 320 drug metabolism, 320, 323 drug reactions, 177 drug resistance, 177 drug therapy, 115, 176, 201, 204 drug treatment, 307, 329 drugs, ix, 4, 7, 12, 55, 60, 66, 67, 68, 70, 74, 88, 121, 128, 133, 134, 135, 136, 138, 139, 157, 165, 168,
Index 170, 172, 175, 199, 201, 202, 203, 204, 232, 234, 240, 252, 260, 266, 271, 286, 290, 292, 293, 294, 297, 302, 303, 304, 305, 307, 308, 309, 311, 318, 319, 321, 322, 323, 324, 329 dumping, 180, 181 dysthymia, 48, 275 dysthymic disorder, 254
E earnings, 261 Eastern Europe, 96 economic development, 67 economic growth, 64 economic status, 21, 234 economic well-being, 44 economy, vii, ix, 30, 59, 61, 63, 71, 197 editors, iv, 40, 113, 159, 160, 161, 308 educational attainment, 77, 81, 126, 261 educational materials, 65, 86 Egypt, 199 elaboration, 171 elderly population, 44, 191, 196, 298, 299, 305 elders, 169 electrocardiogram, 295 Electroconvulsive Therapy, 159 electroencephalogram, 156 electrolyte, 294 emotion, 10, 188, 203, 209, 215, 228, 235, 236, 244, 245 emotion regulation, 215 emotional disorder, 230 emotional distress, 235 emotional reactions, 38 emotional well-being, 44, 275 emotionality, 211, 222 employability, 109, 279 employee compensation, 104 employment, vii, ix, 5, 18, 19, 21, 22, 25, 44, 45, 48, 50, 51, 54, 61, 87, 93, 94, 95, 96, 97, 98, 99, 100, 101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 116, 122, 124, 125, 130, 132, 134, 136, 139, 149, 157, 263, 278, 279, 286 Employment Equity Act, 105 employment status, 5, 22, 25, 51, 61, 94, 96, 97, 98, 99, 108, 111, 112, 122, 125, 132 empowerment, 114 encephalitis, 299 encephalopathy, 294, 302, 306 encouragement, 195
Index endangered species, 320 endocrine, 117, 120, 121, 122, 135, 136, 138, 315 endocrine disorders, 117, 120, 122, 135 end-stage renal disease, 285 endurance, 36 enforcement, 71 England, xi, xvii, 21, 35, 37, 79, 88, 96, 150, 156, 160, 161, 163, 164, 168, 170, 173, 225 environmental factors, 208, 210, 216, 220, 258, 291 enzyme induction, 304 epidemic, 67, 69 epidemiologic studies, 258, 285 epidemiology, xvi, xvii, 55, 110, 114, 133, 135, 281, 285, 286, 287, 306, 308, 309, 311 epileptogenesis, 320 epistemology, 163, 169, 170 equality, 61, 104, 106, 107 equipment, 65, 102, 182 equity, 53, 60, 62, 72, 103 Estonia, 88, 98 estrogen, 117, 323 ethanol, 319 ethics, 5 ethnic background, 5, 301 ethnic groups, xvii, 77, 315 ethnic minority, 31 ethnicity, xiv, 2, 31, 33, 39, 77, 174 etiology, 55, 56, 112, 137, 213, 220, 256, 258, 281, 287, 302, 329 eugenics, 158, 160 euphoria, 322 European Union, 105 evil, 166 examinations, 102 excitability, 323, 324 excitation, 300 exclusion, vii, xvi, 26, 34, 38, 103, 150 excretion, 320 executive function, 79 executive functioning, 79 exercise, 165, 256 expenditures, 177, 178 experiences, vii, ix, xii, 1, 2, 3, 4, 5, 6, 9, 13, 14, 18, 29, 30, 31, 34, 35, 36, 40, 82, 91, 99, 143, 144, 164, 170, 172, 173, 174, 199, 217, 226, 271 exploration, 10, 12, 31, 249, 283 exposure, xiv, 10, 14, 26, 79, 128, 134, 136, 138, 139, 140, 316 external locus of control, 248 externalizing behavior, 198, 211
337
extraversion, 251 eye movement, 295, 299
F facilitators, x, 102, 189, 191, 192, 219, 257, 258, 268 fainting, 298, 322 fairness, 53, 61 faith, 65, 164, 166, 169, 171, 174, 329 false belief, 83 false negative, 20, 21 family conflict, 176 family environment, 123, 216, 220, 229 family factors, x, xiii, 189, 198, 203, 215, 227, 228, 230, 234, 237, 239, 241 family functioning, 193, 215, 218, 240 family history, 187, 248, 258 family interactions, 228, 235, 241 family life, 35, 97, 228, 232, 233, 241 family members, 1, 8, 9, 11, 30, 84, 164, 176, 229, 233, 236, 239, 315 family planning, 65 family relationships, 237, 240 family support, 305 family therapy, 245, 246 farmers, 63 farmland, 63 fasting, 1, 7, 12, 326 fat, 124, 326 FDA, 286 fears, 148, 216, 240 feedback, 198, 269 feelings, 49, 50, 217, 259, 263, 264, 271, 272, 273, 274 fertility, 119, 120, 121, 122, 132, 134, 140 fertility rate, 119, 120, 121, 132, 140 fever, 3, 62, 316 fiber, 320 fibrosis, 180, 203, 205, 231 Fiji, 64 Filipino, 84, 91 films, 38, 154 filtration, 303 financial distress, 187 financial resources, 44, 196, 318 financial support, 150 financial system, 269 Finland, 88, 207, 230 first aid, 318 first generation, 306
338
Index
fishing, 83 flavonoids, 319, 327 flexibility, 209, 237 fluid, 166 focal seizure, 9, 291 focus groups, 34, 167, 171 folic acid, 130, 325, 327 follicle, 120 foundations, 32, 103 fractures, 178, 302 fragility, 291 France, 148, 289, 309 fraternal twins, 258 freedom, 53, 191 frontal lobe, 79, 87, 91, 290, 291, 295 funding, xii, 37, 61, 62, 64, 66, 69, 103, 267, 269 fusion, 270
G gait, 294 Gallup Poll, 87 garbage, 150 gender differences, ix, 7, 35, 115, 116, 117, 118, 123, 126, 127, 130, 132, 138, 231 gender effects, 12 gender role, 124 general anesthesia, 322 general practitioner, 30, 166, 173 generalized seizures, 13, 299, 300, 302 generalized tonic-clonic seizure, 95, 117, 187, 292, 295 genetic factors, 262 genetics, xvii genre, 38 Georgia, xi, xii, xiii, 283 Germany, 96, 118, 137, 285 gingival, 315 ginseng, 323 gland, 119, 325 globalization, 31, 171 glucose, 198, 199, 311 God, 146, 169, 171, 173, 317 Google, 145 government policy, 62 Great Britain, 96, 112 Greece, 147 Greeks, 147 growth rate, 63 guidance, xvi, 129, 195, 198, 208, 219, 249, 251, 285
guidelines, 118, 129, 131, 134, 136, 266, 270, 309 guilt, 129, 250, 253 guilty, 155, 156, 161, 269
H hair, 124, 141, 182, 201, 203, 205 hair loss, 124 hallucinations, 151, 294, 322 happiness, 122, 124 harassment, 105 harmony, 191 hazards, 294 head injuries, 66 head injury, 116, 132 head trauma, 314 headache, 6, 10, 12, 305, 321, 322, 323, 324, 325 health care costs, 64, 178, 260, 304 health care professionals, 84, 127, 130, 137 health care system, 35, 164, 173, 267, 270 health education, 65, 86 health expenditure, 61 health information, 73, 75, 76, 78, 83, 88, 276, 280 health insurance, 61, 62, 63, 78 health locus of control, 16 health problems, 32, 34, 50, 100, 124, 125, 202, 208, 218, 219, 220, 221, 229, 231, 243, 266, 278 health psychology, xiii, 201 health services, xii, xvi, 26, 60, 61, 62, 63, 64, 65, 69, 85, 166, 266, 267, 275, 277, 283, 284, 286 health status, 44, 57, 58, 283 health systems, ix, 59, 60, 61, 69, 163, 269 health-promoting behaviors, 217 heart disease, xii, 24, 58, 255, 260, 278, 285 heartburn, 323 heavy metals, 320 hegemony, 170 height, 124, 148, 158 helplessness, 49, 50, 52, 54, 57, 255, 264 hematoma, 299 herbal medicine, x, 66, 313, 319, 320 heredity, 147 heterogeneity, 229, 241 high blood pressure, 322, 323 high school, 5, 77, 78 hippocampus, 300, 320 Hispanic population, 31 Hispanics, 31, 32, 77 HIV/AIDS, 24, 25, 66, 67, 68, 90, 144 Hmong, 31, 33, 34, 39, 84, 88, 90, 164, 172
Index holistic care, 170 home ownership, 80 homeostasis, 324 homework, 271 Honduras, xvii, 313, 314, 316, 317, 318, 329 honesty, 217 Hong Kong, 56, 70, 105, 277 hookworm, 66 hopelessness, 263 hospitalization, 30 host, 252 hostility, 191, 228, 235, 240, 260 household income, 81, 82 housing, 8, 80 hue, 151 human immunodeficiency virus (HIV), 24, 25, 26, 66, 67, 68, 70, 90, 105, 144, 159, 203, 205, 324 human performance, 143, 144, 145, 146, 151, 158 human resources, 101 human rights, 103 Hungary, 9, 26, 81, 89 hunting, 147 husbandry, 144 hybrid, ix, 163, 165 hybridity, 164, 171, 174 hygiene, 190 hyperactivity, 190, 214, 215, 223, 224, 230, 231, 321 hyperandrogenism, 136 hypercholesterolemia, 23 hyperplasia, 315 hypersensitivity, 294, 295 hypertension, 23, 58, 128, 201, 262, 266, 303, 323, 324, 325 hypnosis, 151 hypoglycemia, 293, 322, 323 hypokalemia, 322 hyponatremia, 292, 293, 304 hypotension, 294, 295, 306, 322 hypothalamus, 119 hypothermia, 324 hypothesis, 4, 11, 23, 236, 237, 291
I iatrogenic, 158 Iceland, 80 ideal, 71, 158, 177, 319 ideals, 145 identical twins, 258 idiopathic, 74, 116, 203, 213, 215, 223, 224, 293
339
idiosyncratic, 45, 46 image, 107, 124, 217 imagery, 37, 325 images, 36, 40 immigrants, 31, 33, 34, 35 immigration, 31, 33, 49 immunodeficiency, 203, 324 impacts, 64, 116, 123, 183, 236, 259 impairments, 49, 79, 104, 114, 218, 219, 308 imports, 68 impulses, 152 impulsive, 215, 218 impulsivity, 230 in transition, 173 in utero, xiv, 128, 134, 135 inattention, 191, 215, 219, 231 incarceration, 148, 150, 151, 152, 156 incidence, 88, 97, 100, 109, 116, 118, 119, 120, 128, 129, 132, 137, 139, 140, 141, 154, 178, 278, 290, 291, 293, 299, 301, 302, 325, 329 incompatibility, 146 independence, 45, 46, 49, 94, 104, 186, 216, 252 India, 33, 36, 63, 64, 65, 68, 70, 71, 80, 91, 96, 105, 114, 140, 170, 173, 174, 329 Indians, 64 indigenous peoples, 33 indirect costs, 30 indirect effect, 287 individual character, 229 individual differences, 126 individualism, 32 inducer, 304 induction, 304 inequity, 60, 107 infant mortality, 158 infants, 85, 88, 140, 205, 220, 326 infarction, 249, 310 infertility, 117, 119, 120, 132 inflammation, 262 informal sector, 62 information sharing, 267 information technology, 103 ingestion, 180, 182 inheritance, 152 inhibition, 211, 300, 319 inhibitor, 310, 324 initiation, 131, 132, 189, 277 inmates, 148 insane, 148, 149, 152, 156, 157 insanity, 81, 100, 155, 156, 161
340
Index
insecurity, 216 insomnia, 295, 305, 321, 322, 323, 324 Institute of Education Sciences, 91 institutionalisation, 49 instructional materials, 76 insulin, 199, 202, 205 integration, ix, 53, 73, 81, 107, 153, 238, 239, 276, 285 intellectual property, 71 intelligence, 79, 98, 139, 215, 216, 223, 251, 252, 254 interdependence, 238 interface, 154, 156, 162 interference, 98, 158, 263, 323 internalised, 144 internalizing, 176, 190, 191, 198, 212, 216, 230, 232 internist, 249 internship, xiii interpersonal communication, 83 interpersonal interactions, 49 interpersonal relations, 44, 48, 260, 287 interpersonal relationships, 44, 48, 260, 287 interpersonal skills, 266, 272 interrelations, 21, 25 intervention, x, xiii, 2, 4, 14, 32, 37, 48, 70, 85, 91, 109, 114, 152, 157, 158, 167, 175, 184, 191, 193, 194, 196, 197, 199, 208, 219, 225, 228, 239, 240, 241, 251, 253, 254, 274, 275, 277, 279, 285 intervention strategies, 70, 175 intoxication, 251 IQ scores, 79 Iran, 3, 54, 187 Iraq, 96, 107 Ireland, 96, 105 iron, 85, 88 irony, 152, 153, 156 irritability, 2, 6, 10, 12, 47, 158, 253, 259, 322 ischemia, 322 isolation, 36, 45, 48, 81, 97, 98, 120, 252, 263 Israel, 106, 295, 306, 309 Italy, 21, 25, 87
J Japan, 98, 267 job performance, 263, 283 job training, 104, 106 Jordan, 106, 171, 173 jurisdiction, 49
K Kentucky, xiv, 93 Kenya, 113 kidney, 303, 322, 323 kidney stones, 322 knees, 36 Korea, 83, 96, 105, 112, 258, 267 Kuwait, 107
L labeling, 23 labor force, 21 laboratory tests, 294, 297 labour force, 21 lack of control, 2 landscape, 32, 39 language barrier, 32, 33 language impairment, 224 languages, 65, 66, 84, 259 Laos, 64, 65, 67 later life, 49, 123, 128, 306 laterality, 119, 135, 256, 311 Latin America, 97, 109, 261, 278, 314 lawyers, 152 learned helplessness, 52, 54 learning, 35, 76, 82, 105, 123, 154, 223, 248, 251, 268, 271 learning disabilities, 105, 223 legal protection, 107 legislation, ix, 24, 93, 94, 103, 104, 152 leisure, 16, 97 lesions, 210, 213, 290, 291, 297, 300, 302 leukopenia, 322 level of education, 78, 96, 98, 234 life expectancy, 236 life quality, 240 life satisfaction, 44, 50, 286 lifestyle behaviors, 202, 262 lifestyle changes, 4, 252 lifetime, xi, 46, 57, 97, 123, 223, 252, 258, 261 limb weakness, 6, 12 Limitations, 13 liquid chromatography, 182, 203 liquids, 317 literacy, ix, 31, 32, 73, 74, 75, 76, 77, 78, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 91, 275 liver, 303, 304, 315, 321, 322, 323, 324
Index liver damage, 323 liver failure, 323 living arrangements, 5, 44 living conditions, 66, 150 lobbying, 25, 149 lobectomy, 54, 55, 89 localization, 121, 298, 302 locus, 16, 47, 157, 189, 201, 248, 255 loneliness, 217 longitudinal study, 260 loss of appetite, 250, 323 loss of consciousness, 292, 293, 294, 297, 322 lung disease, 262
M macrobiotics, 168 magazines, 37, 83, 87 mainstream society, 34 major depression, 56, 248, 250, 252, 253, 264, 265, 269, 275, 278, 281, 282, 283, 284, 286, 287 major depressive disorder, 46, 47, 48, 253, 254, 258, 281, 287 majority, 6, 9, 21, 50, 64, 68, 76, 83, 94, 95, 96, 101, 120, 207, 211, 214, 218, 224, 251, 269, 276, 291, 294 malaria, xii, 66, 159, 316 malnutrition, 83, 150, 303 maltreatment, 259 mammography, 84 management, ix, xi, xii, xiii, xvi, xviii, 13, 31, 44, 48, 52, 53, 54, 65, 71, 73, 75, 84, 85, 86, 87, 89, 90, 112, 114, 115, 131, 134, 143, 144, 153, 154, 158, 159, 165, 176, 184, 189, 190, 191, 193, 194, 195, 196, 197, 198, 199, 200, 201, 202, 203, 240, 242, 251, 262, 266, 268, 269, 270, 271, 272, 274, 275, 276, 277, 278, 280, 281, 282, 283, 284, 286, 287, 302, 309, 311 mania, 47, 151, 322, 323, 324 manic, 323 manic episode, 323 manufacture, 68, 154 manufacturing, 320 marginalization, 34, 38 marital status, 5, 81, 105, 122, 125, 187, 253 marriage, 33, 40, 49, 116, 120, 122, 124, 125, 132 married women, 125 marrow, 204, 315 Marshall Islands, 64 Marx, 150
341
mass media, 83, 87 mass spectrometry, 182 matrix, 24 media, 32, 40, 78, 83, 87, 112, 154 median, 102, 116, 301 Medicaid, 78 medical care, 44, 63, 69, 73, 113, 150, 170, 193, 198, 199, 280 Medicare, 78 medication, xi, xiv, 1, 2, 3, 7, 11, 12, 15, 44, 48, 52, 71, 85, 87, 91, 104, 129, 130, 137, 141, 161, 163, 170, 178, 179, 180, 181, 182, 183, 184, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 200, 201, 202, 203, 205, 224, 230, 232, 233, 240, 242, 247, 248, 251, 252, 253, 255, 261, 266, 268, 271, 272, 276, 277, 290, 292, 304, 305 medication adherence, xi, 181, 187, 188, 193, 194, 196, 197, 202, 203, 205, 255, 276 medication compliance, 200, 201, 242, 252 medicines, vii, x, 60, 64, 66, 67, 68, 69, 72, 174, 317, 320 melatonin, 326 membership, 105 memory, xv, 79, 89, 90, 128, 184, 263, 268, 279 menarche, 134 meningismus, 323 meningomyelocele, 325 menopause, 117, 127, 130, 134, 323 menstruation, 1, 3, 7, 12, 117, 158, 323 mental disorder, 145, 148, 151, 153, 166, 174, 247, 248, 249, 261, 264, 267, 273, 277, 283 mental health, 32, 33, 34, 41, 44, 48, 84, 100, 124, 125, 126, 127, 129, 132, 139, 152, 155, 156, 208, 218, 219, 220, 221, 222, 224, 229, 233, 240, 243, 265, 266, 267, 269, 270, 276, 277, 278, 283, 284, 285 mental health professionals, 84, 265, 277 mental illness, xii, 33, 83, 152, 162, 249, 264, 267, 279, 280 mental life, 251 mental retardation, 213, 215, 220, 224, 236 meridian, 324 meta-analysis, 116, 128, 137, 197, 200, 204, 218, 223, 225, 230, 245, 260, 272, 273, 278, 280, 285, 286, 287, 325 metabolic disorder, 290, 297 metabolic disturbances, 289 metabolism, 185, 303, 304, 311, 320, 322, 323, 324 metals, 320 methodology, xi, 10, 32, 164, 187, 237, 249, 319
342
Index
Mexico, 319 mice, 140, 300, 319, 320, 326, 327, 328 migrants, 172 migration, 35, 128 mind-body, ix, 143, 145, 157, 158 minorities, 31, 33 minority groups, 32, 35 misconceptions, 31, 32, 37, 83 misunderstanding, 49, 97 modelling, 60 moderates, 152 moderators, 208, 215, 218, 220 modern society, 124 modification, 102, 187, 196, 222, 272 Mongolia, 64 monitoring, 2, 63, 71, 149, 176, 180, 182, 184, 185, 193, 194, 196, 199, 200, 201, 205, 269, 270, 298, 306, 308, 309 monoamine oxidase inhibitors, 271 mood change, 259 mood disorder, 46, 51, 116, 126, 153, 250, 252, 253, 255, 278, 281 mood states, 51, 54, 252 Moon, 88, 154, 161 moratorium, 252 morbidity, 46, 55, 126, 150, 168, 175, 176, 177, 180, 248, 255, 281, 282, 305 morphology, 299 mortality rate, 83, 118, 302 motivation, 164, 188, 196, 251, 252, 265, 273, 274, 284 motor activity, 294 movement disorders, 297, 298 MRI, 295, 297, 298 multidimensional, 209 multiple factors, x, 46, 182, 263, 303 multiple sclerosis, xiv, 109, 275, 284 murder, xvii, 143, 152, 155, 156, 162 music, x, 36, 39, 313, 325 Muslims, 174 mutation, 145, 310, 311 myalgia, 297 myocardial infarction, 249 myoclonus, 294, 300, 308, 311 myopathy, 322, 327 mythology, 146, 152
N narcotics, 321
narratives, xv, 30 National Center for Education Statistics, 89, 91 national emergency, 68 National Health Service, 69, 166 national income, 64 National Institutes of Health, xiii, xvii, 41, 89 nausea, 6, 12, 195, 295, 322, 323 negative attitudes, 50, 98, 99, 107, 124 negative consequences, 101 negative mood, 272 negative relation, 98, 193 neglect, 34, 187 negotiating, 33, 67 nerve, 52, 57, 74, 91, 315 nervous system, 188, 208, 212, 224, 231, 320, 324 Netherlands, 78, 96, 328 neural network, 308 neural networks, 308 neurobiology, 146 neurodegeneration, 134, 138 neurofibrillary tangles, 300 neurogenesis, 128 neuroimaging, xv, xvi neurological disease, xv, xvii, 299, 314, 327 neurologist, 2, 12, 64, 153, 249 neurons, 311, 320, 324 neuropathy, 145, 303, 311 neurophysiology, xiii, xv, 145 neuroprotection, 320 neuropsychiatry, 143, 145, 153, 154, 161, 162 neuropsychological tests, 79 neuropsychology, xi, xvi, 153 neuroscience, xv, 145, 153, 242 neurosyphilis, 299 neurotransmission, 313, 324 neurotransmitter, 259, 300 New England, xi, xvii, 225 New South Wales, xii New Zealand, xii, xvi, 26, 173 Nigeria, 66, 70 Niue, 64 non-steroidal anti-inflammatory drugs, 322 normal aging, 299, 308, 311 normal children, 214 North America, 113, 140, 148 Northern Ireland, 105 Norway, 3, 223, 226 nurses, 83, 161, 184 nursing, xi, xii, 54, 149, 161, 242 nutrition, 31, 316
Index
O obesity, xiii, 83 occupational therapy, xiv oil, 155, 319, 321, 322 one dimension, 38 opiates, 252 opportunities, vii, ix, 4, 18, 19, 45, 93, 94, 103, 252 Opportunities, 105 optimism, 45 optimization, 73 organizing, 247 orthostatic hypotension, 294, 295, 306 osteomalacia, 304 osteoporosis, 130, 315, 325 otherness, 35 outpatients, 51, 58, 98, 101, 255 ovaries, 117, 136 overlap, 268 overseas aid, 69 ovulation, 1, 7 ovum, 120 ownership, 80
P Pacific, 64, 72, 77 Pacific Islanders, 77 pain, 44, 122, 253, 259, 260, 282, 295, 322, 323, 325 Pakistan, 3, 15, 164, 166, 167, 168, 169, 170, 172, 173, 174 panic disorder, 250 parallel, 164, 165, 166, 168, 171, 305 paralysis, 148, 157 paranoia, 47 parental attitudes, 231, 235, 243 parenting, xiii, 216, 218, 233, 235, 236, 237, 245, 246 parenting behaviours, 236 parenting styles, 216 paresis, 292 parity, 267 parkinsonism, 301, 307, 310 partial seizure, 2, 6, 7, 8, 13, 35, 47, 51, 95, 117, 135, 139, 221, 225, 232, 243, 245, 291, 292, 295, 300 patents, 68 pathogenesis, 24, 54, 140, 254 pathology, 152, 157, 158, 259, 300 pathophysiology, 82
343
pathways, 208, 218, 219, 329 patient care, xvii, 34, 249 peer rejection, 211 peer relationship, 212, 217 penalties, 146 penis, 158 perceived control, 4, 256 perfectionism, 143, 145 performance, 37, 61, 78, 79, 87, 111, 143, 144, 145, 146, 151, 158, 182, 203, 209, 211, 221, 263, 271, 274, 283, 300 perfusion, 303 peripheral neuropathy, 311 permission, iv perpetrators, 147 perseverance, 38 personal accounts, 168 personal control, 139 personal goals, 208 personal identity, 50, 94 personality traits, 227 persons with disabilities, 94, 103, 104, 105, 109 PET, 250, 311 pharmaceuticals, 67, 71, 156, 205 pharmacokinetics, 303, 309 pharmacological research, vii, viii pharmacological treatment, 168, 169 pharmacology, 145, 180 pharmacotherapy, 326 phenomenology, 56, 137, 256 phenothiazines, 322 phenotype, 301, 310 phenytoin, 67, 128, 200, 203, 303, 304, 311 Philippines, xii, xiii, 72 photosensitivity, 324 physical activity, 247, 316 physical health, 44, 124, 281, 285 physical treatments, 157 physiological factors, 11 physiology, 3, 147, 188, 250 pilot study, 109, 276, 280, 286 pineal gland, 325 plants, 319, 320, 327, 328 plasma levels, 139, 182, 189, 203, 205 plasticity, 139 pleasure, 259, 269 pluralism, 170, 173 poetry, 36 police, 95, 112 policy makers, 27
344 policy reform, 277 politics, 169 polycystic ovarian syndrome, 119 poor performance, 79 positive attitudes, 84, 217 positive correlation, 250, 320 positive interactions, 260 positive reinforcement, 219 positive relationship, 193, 208, 209, 217 positivism, 146 postnatal exposure, 140 poverty, 62, 63, 66, 68, 74, 77, 169 poverty line, 63, 68 praxis, 34 prayer, x, 325 precedent, 37 predictability, 308 predictive validity, 203 predictor variables, 22, 81 prefrontal cortex, 139, 311 pregnancy, 1, 7, 12, 66, 127, 128, 129, 130, 131, 132, 134, 135, 136, 138, 140, 141, 158, 205, 325, 327 prejudice, 49, 80, 81, 152, 263 prejudices, vii, 49, 154, 249 preschool, xvi, 214, 217, 219, 221, 224, 225, 245 preschool children, xvi, 221, 224, 225, 245 preschoolers, 222 prestige, 170 preterm delivery, 128 prevention, 55, 76, 88, 140, 283, 307, 326 primary school, 112 probe, 183 problem behavior, 210 problem behaviors, 210 problem drinking, 273 problem solving, 209, 216, 228, 236, 237, 253 problem-focused coping, 236, 241 problem-solving, 197, 198, 237, 275 procurement, 71 prodromal symptoms, 295 productivity, 30, 201, 259, 260, 261, 280, 283, 286 prognosis, 15, 57, 90, 114, 137, 157, 225, 246, 293, 302, 309 project, 37, 65, 67, 68, 88, 121, 171, 240, 277 proliferation, 168 pronunciation, 75 proposition, 157, 158 prosocial behavior, 210, 211, 212, 219 protective factors, 216, 217, 219
Index psychiatric diagnosis, 211, 215 psychiatric disorders, 227, 229, 238, 247, 249, 250, 259, 293, 295, 306, 322 psychiatric illness, xvi, 248 psychiatric morbidity, 255, 282 psychiatric patients, 307 psychiatrist, xv, xvi, 148, 152, 153, 156, 249, 270 psychiatry, xv, xvi, 113, 148, 149, 151, 152, 153, 155, 156, 157, 162, 228, 247, 248, 249, 250, 270 psychoanalysis, 144, 249, 285 psychological adaptations, 38 psychological distress, 22, 48, 52, 53, 121, 259 psychological problems, 228, 232, 233, 234, 238 psychological states, 34 psychological well-being, 51, 88, 135, 140, 263 psychologist, xiv, xvi, xvii, 277 psychology, xi, xiii, xiv, xvi, 55, 136, 139, 144, 156, 157, 161, 165, 201, 204, 224, 231, 272, 287 psychometric properties, 183 psychopathology, x, 47, 50, 53, 56, 135, 189, 208, 211, 212, 213, 214, 215, 218, 225, 227, 228, 229, 230, 231, 232, 233, 234, 236, 237, 238, 240, 241, 243, 245, 255 psychopathy, 151 psychopharmacology, 84 psychoses, 157 psychosis, 153, 230 psychosocial conditions, 18 psychosocial development, 208, 219, 224 psychosocial factors, xi, 16, 47, 120, 122, 126, 218, 314 psychosocial functioning, 48, 49, 93, 94, 98, 123, 188, 232, 253 psychosomatic, 245 psychosurgery, 157 psychotherapy, xvii, 55, 144, 157, 254, 272, 274, 275, 279, 281, 283, 284, 286 psychoticism, 251 psychotropic drugs, 292, 297, 311 puberty, 124, 131 public awareness, 89 public domain, 29 public education, viii, 29, 30, 31, 32, 83, 88 public finance, 63 public health, 60, 62, 64, 65, 66, 69, 75, 80, 83, 107, 247, 248, 267, 276, 277, 278 public opinion, 37 public policy, 109, 110 public sector, 169 public service, 64, 166
Index public-private partnerships, 67 pulmonary hypertension, 323 punishment, 83, 156 purpura, 322
Q quality of life, viii, ix, xi, xiii, xiv, xviii, 17, 18, 31, 43, 44, 45, 46, 48, 49, 50, 52, 53, 54, 55, 56, 57, 58, 82, 87, 93, 107, 112, 114, 121, 124, 133, 134, 154, 168, 176, 177, 180, 188, 197, 201, 216, 222, 225, 226, 233, 240, 242, 244, 245, 246, 247, 248, 254, 257, 258, 260, 261, 262, 263, 264, 267, 272, 276, 278, 279, 282, 283, 284, 286, 287, 302, 308, 309, 314 questioning, 183
R race, 33, 81, 105, 158, 265 racism, 33 randomized controlled clinical trials, 193 rapid eye movement sleep, 295, 299 rash, 305, 322, 323 rating scale, 211 reactions, 18, 19, 38, 45, 144, 177, 198, 214, 315, 322, 324 reactivity, 238, 239 reading, 32, 75, 76, 86 reading comprehension, 75, 86 reading skills, 75 reality, 44, 100, 105, 152, 200 reasoning, 153, 203, 248, 254 recall, 86, 99, 179, 184 receptors, 319, 320 recognition, xi, 2, 23, 31, 54, 75, 177, 209, 254, 256, 257, 258, 265, 266, 267, 268, 269, 277, 278, 287, 308 recommendations, iv, 12, 31, 147, 175, 176, 190, 195, 199, 200, 203, 243, 266, 267, 271, 303 reconstruction, 202 recruiting, 103, 105 recurrence, 198, 272, 273, 287, 290, 292, 302 reductionism, 250 reforms, ix, 59, 60, 63 refugees, 31, 33 regression, 21, 22, 82, 140 regression analysis, 22
345
rehabilitation, xiv, xvii, 62, 66, 89, 94, 103, 106, 108, 109, 110, 113 Rehabilitation Act, 103, 112 rehabilitation program, 106 reinforcement, 194, 197, 200, 219, 274 rejection, 168, 221, 235, 253 relationship quality, 236, 237 relatives, 168, 232, 315, 318, 327 relaxation, 4, 7, 14, 273, 313, 325 relevance, 17, 18, 249, 256 reliability, 19, 137, 185, 200 religion, 105, 146, 152 religious beliefs, 164 remission, 45, 50, 96, 100, 104, 111, 272, 275 replacement, 272 replication, 283 reproduction, 17, 18 reputation, 143, 156 resilience, 38, 208, 216 resistance, 177, 216 resolution, 238 resources, vii, 32, 33, 34, 44, 61, 63, 64, 66, 73, 101, 106, 107, 187, 196, 216, 233, 236, 241, 259, 262, 267, 269, 314, 316, 318, 327 responsiveness, 90 restless legs syndrome, 295 restructuring, 61, 62, 63, 67, 102, 253, 269, 275 retardation, 84, 213, 215, 220, 224, 226, 236 retirement, 50 revenue, 62, 63 rhythm, 295, 299 rights, viii, 31, 76, 94, 103, 104, 106, 107, 110, 267 risk factors, 47, 116, 127, 132, 136, 137, 140, 208, 213, 216, 218, 219, 233, 241, 243, 244, 255, 262, 277, 282, 285, 286, 308 routines, 196 rural areas, 64, 65, 80, 96, 315 rural people, 69 rural population, 68, 71, 166 Russia, 267, 284
S sadness, 259 saliva, 179, 182, 186, 190 SARS, 83 Saudi Arabia, 199 savings, 277 scaling, 60, 89 schema, 49, 239, 241
346 schizophrenia, 144, 148, 157, 223, 250, 285 schooling, 78, 123 scientific knowledge, 38 scientific method, 249 scientific understanding, 30 sclerosis, xiv, 79, 109, 275, 284 screening, 55, 75, 81, 82, 84, 91, 173, 266, 268, 269, 270, 274, 277, 281, 286 second generation, xiv, 35 secretion, 117, 119, 121 sedative, 292, 293, 304, 323, 328 segregation, 148 selective serotonin reuptake inhibitor, 250, 304, 324 self esteem, 124 self help, 277 self-concept, 217, 231, 238 self-confidence, 106 self-control, 4, 5, 9, 11, 12, 15, 16, 211, 237 self-efficacy, 45, 98, 106, 202, 216, 246, 264, 274, 276, 280 self-esteem, 38, 44, 49, 50, 98, 107, 215, 216, 217, 231, 236, 262, 264 self-expression, 37 self-image, 107, 217 self-management behaviors, 274, 277 self-monitoring, 193, 196 self-perceptions, 232 self-regulation, 202, 211 self-reports, 23, 236 sensation, 296 sensations, 273 sensitivity, 117, 137 serotonin, 250, 258, 271, 304, 324 serotonin syndrome, 324 serum, 176, 177, 178, 179, 180, 182, 185, 186, 187, 189, 190, 193, 297, 321, 323, 324 service provider, 61, 167, 172 SES, 80, 187, 198 sex, 78, 96, 105, 116, 117, 119, 132, 139, 187, 250, 251, 307, 311 sex differences, 117, 139 sex steroid, 119, 132 sexual abuse, 251 sexual activities, 134 sexual activity, 122, 254, 316 sexual orientation, 105 sexuality, xvii, 120, 138 shame, ix, 26, 50, 143, 144, 217 shape, 34, 165 shelter, 67, 106
Index short supply, 66, 145 shortage, 24, 130 sibling, 235 siblings, 204, 212, 217, 219, 226, 229, 231, 234, 241 sickle cell, xiii, 203 side effects, 14, 50, 74, 124, 184, 185, 188, 190, 192, 195, 198, 263, 265, 271, 303, 304, 305, 321, 322, 323, 324 signals, 107 significance level, 5 signs, viii, 1, 2, 4, 5, 6, 9, 11, 12, 13, 14, 144, 213, 250, 297, 302, 307 Sinai, xv, 29 Singapore, 3, 16 skills training, 194 skin, 305, 323, 324, 325 sleep deprivation, 1, 3, 7, 10, 12, 13 sleep disturbance, 253, 268, 309 smoking, 83, 262, 273, 279 smoking cessation, 273 sociability, 213 social acceptance, 31, 69, 84, 99, 209 social activities, 43, 45, 217, 263 social adjustment, 209, 227, 237, 256 social behavior, 222, 241, 325 social capital, xvi social care, xiv, 146, 159, 167, 173 social change, 46, 150 social class, 79 social cognition, 221 social competence, ix, xvi, 207, 208, 209, 210, 211, 212, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 231, 238 social consequences, 17, 18, 27, 50 social context, 32, 35, 101, 149, 155, 164, 165, 203, 209, 218 social control, 149, 151, 152 social desirability, 22, 184, 198 social development, 208, 217, 219, 232, 238 social deviance, 144, 145, 146 social environment, 35, 150, 209, 216, 217 social events, 45 social exclusion, vii, xvi, 26, 34, 150 social group, 151 social identity, 23, 111, 282 social integration, 107 social justice, viii social network, 45, 165, 216 social order, 143, 144 social participation, 94, 97, 208, 217
Index social problems, x, 98, 110, 124, 209, 212, 215, 227, 230, 231, 232, 238, 241 social sciences, viii, 29, 30, 38 social situations, 101, 210, 235, 263 social skills, 123, 207, 208, 209, 210, 211, 212, 213, 215, 218, 219, 221, 222, 231, 240 social status, 2, 125, 134, 170 social structure, viii social support, 45, 47, 53, 107, 124, 198, 223, 233, 236, 253, 263, 274, 276, 286 social welfare, 61 social withdrawal, 211, 230, 232, 238 socialization, xviii socioeconomic background, 24 socioeconomic status, 80, 176, 187, 193, 234, 264 sodium, 140, 322 somnolence, 315 South Africa, 67, 71, 105, 258, 287 South Asia, 34, 164, 166, 167, 168, 169, 170, 172, 173, 174 South Korea, 83, 96 Southeast Asia, 25 Spain, xv, 227 spastic, 310 specialists, 64, 277 species, 320, 321, 323 speech, 6, 11, 12, 36, 237, 292, 321 sperm, 87, 121, 132 spin, 146 spinal cord, 325 spirituality, 265 spontaneous abortion, 128 sprouting, 320 Sri Lanka, xii, 33 staffing, 66 standardization, 320 stars, 37 statistics, viii, 17, 18, 19, 21 status epilepticus, xvi, 31, 39, 118, 134, 136, 137, 140, 177, 291, 292, 294, 299, 300, 302, 306, 309, 310 stenosis, 294 stereotypes, 38, 49 stereotyping, 23 stigma, viii, ix, xi, 17, 19, 22, 23, 24, 25, 26, 27, 29, 30, 31, 32, 33, 36, 37, 38, 39, 43, 45, 46, 47, 48, 49, 50, 52, 53, 55, 56, 57, 64, 80, 82, 83, 97, 99, 100, 102, 107, 108, 110, 111, 112, 113, 143, 144, 146, 151, 154, 157, 159, 160, 190, 198, 217, 222, 223, 225, 232, 233, 243, 244, 247, 248, 252, 253,
347
255, 263, 264, 265, 268, 276, 277, 278, 279, 282, 315, 318 stigmatized, ix, 253, 264, 315 stomach, 195, 322, 324 storage, 88 streams, 269 stressful life events, 262 stressors, 124, 236, 259, 276 stroke, x, 66, 116, 132, 289, 293, 295, 301, 303, 306, 307, 308, 310, 314, 322 subdomains, 209 subdural hematoma, 299 subgroups, 31, 121 subjective experience, ix, xii, 2, 3, 5, 13, 14, 143, 144 sub-Saharan Africa, 32, 39, 97, 112 substance abuse, xvi, 196, 252 substance use, 250, 252 substitution, 68 suicidal behavior, 136 suicidal ideation, 47, 255, 271, 278, 282 suicide, 47, 54, 57, 127, 134, 135, 140, 247, 248, 253, 254, 255, 256, 259, 261, 282 suicide attempts, 54, 127, 255, 282 suicide rate, 47, 261 supernatural, x, 147, 148, 166, 314, 315 supervision, 60, 129, 149, 184, 191, 196, 203 supervisor, 101 support services, 173 suppression, 324 Supreme Court, 104 surgical intervention, 45 surveillance, 80, 112, 118, 149 survey, viii, 5, 15, 19, 20, 22, 23, 25, 26, 31, 54, 55, 58, 64, 76, 77, 78, 79, 80, 81, 83, 85, 87, 95, 96, 98, 100, 102, 108, 109, 110, 134, 137, 138, 139, 140, 201, 202, 221, 223, 243, 252, 276, 283, 309, 317, 318 survivors, 151 susceptibility, 4, 117, 126, 132, 139, 140, 250, 290, 300 Sweden, 225, 244 Switzerland, 84, 87, 118, 134, 205 sympathy, 38 symptoms, viii, x, 1, 2, 4, 5, 6, 9, 10, 12, 13, 14, 15, 16, 22, 44, 47, 48, 50, 58, 144, 170, 176, 191, 198, 213, 227, 230, 231, 236, 238, 242, 250, 251, 253, 254, 256, 259, 260, 262, 264, 265, 266, 268, 270, 271, 272, 275, 276, 278, 281, 283, 284, 285, 287, 289,292, 293, 294, 295, 300, 315, 319, 322, 324, 325
348
Index
syndrome, 88, 119, 124, 129, 132, 133, 136, 139, 213, 214, 220, 230, 250, 293, 296, 309, 324 syphilis, vii, 148
T tachycardia, 322, 323 tactics, 68 Taiwan, xiv, 3, 258, 267 tangles, 300 Tanzania, 80, 141 target variables, 81 technical assistance, 105 teenage girls, 124 teens, 216, 226 teeth, 36, 196 telecommunications, 104 temperament, 216, 236 temperature, 316 temporal lobe, 13, 15, 33, 47, 54, 55, 56, 57, 79, 88, 89, 119, 135, 136, 160, 221, 251, 252, 254, 285, 291, 298, 302, 320, 329 temporal lobe epilepsy, 13, 15, 33, 47, 56, 57, 79, 88, 119, 136, 160, 221, 251, 254, 285, 320, 329 tension, 23, 158 terminal illness, 23 territory, 297 tertiary syphilis, 148 testing, 12, 179, 193, 196, 197, 199, 249, 251, 277, 294 testosterone, 117, 121, 139 Thailand, 61, 62, 71, 111 therapeutic approaches, 228 therapeutic intervention, 48 therapy, xiv, 51, 68, 71, 74, 84, 91, 115, 117, 118, 120, 135, 150, 156, 158, 163, 175, 176, 178, 180, 182, 184, 190, 192, 193, 194, 201, 203, 204, 205, 245, 246, 250, 265, 271, 272, 274, 275, 277, 280, 281, 282, 283, 284, 285, 286, 287, 290, 303, 305, 314, 325, 326, 329 Third Reich, 158 Third World, 70 thoughts, 144, 158, 253, 259, 271, 273, 274, 324 thrombocytopenic purpura, 322 time constraints, 269 time frame, 6, 9, 183 time use, 141 tissue, 158 Title I, 104 tobacco, 196, 252
toddlers, 131 Togo, 57 tones, 322 tonic, 2, 6, 35, 51, 95, 117, 187, 188, 264, 291, 292, 295, 297, 322 tonic-clonic seizures, 51, 95, 117, 187, 188, 264, 291, 292, 322 torticollis, 323 toxic side effect, 303 toxic substances, 320 toxicity, 304, 315, 323, 324 trade-off, ix traditional practices, 169 traditions, 4, 167, 171 training, xii, xvi, xvii, 60, 64, 65, 66, 85, 90, 94, 102, 104, 105, 106, 149, 158, 185, 194, 268 trait anxiety, 126 traits, 38, 209, 227, 228, 251 trajectory, 44 transformation, 34, 172 transfusion, 83 transient ischemic attack, 289, 292, 295, 297 transmission, xii, 148, 243 transplantation, 200, 204 transport, 62 transportation, 49, 77, 102, 103, 104, 106, 265, 319 trauma, 116, 118, 291, 293, 314, 316 traumatic brain injury, 110 traumatic events, 259 treatment methods, 11, 153, 268 tremor, 322 trial, xii, 51, 56, 57, 74, 89, 91, 188, 196, 199, 200, 204, 205, 244, 253, 275, 276, 278, 279, 283, 285, 287, 305, 310, 329 triangulation, 239 tribesmen, 317, 318 tricyclic antidepressant, 271, 301, 323 tricyclic antidepressants, 271, 301, 323 triggers, viii, 1, 5, 6, 7, 10, 12, 13, 14, 148 Trinidad and Tobago, 114 tryptophan, 250 tuberculosis, vii, 66, 148, 159 tumours, 291 type 1 diabetes, 245, 246
U underlying mechanisms, 153, 221 unemployment rate, 94, 95, 96 unhappiness, 158
Index United Kingdom (UK), v, ix, xi, xii, xiv, xvi, xvii, 3, 25, 26, 31, 34, 37, 39, 40, 49, 53, 55, 69, 79, 80, 98, 100, 105, 111, 115, 120, 128, 136, 138, 139, 143, 145, 161, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 221, 229, 242, 266, 282, 307 universal access, 69 urban area, 64, 96 urban areas, 64, 96 US Department of Health and Human Services, 33, 41 use of force, 316
V vagina, 158 vagus, 52, 57, 74 vagus nerve, 52, 57, 74 validation, 107, 148, 184, 298 variations, 230, 306 vascular dementia, 290, 301 vascular diseases, 301 vasovagal syncope, 295 vegetable oil, 321 vein, 147 vertigo, 295 victims, 99 video, 36, 37, 39, 194, 289, 298, 306, 308 videos, 36, 37, 39, 194 Vietnam, 32, 62, 63 violence, 152 vision, 29 visual acuity, 294 vitamin D, 325 vitamins, 325 vocational rehabilitation, 103, 106, 113 vocational training, 85, 106 vomiting, 295, 323 vulnerability, 38, 191, 229, 262, 273 vulnerability to depression, 262
water supplies, 69 watershed, 45 weakness, 6, 12, 259, 321, 322 wealth, 128 web, xiii, 86, 154, 171, 275, 326 websites, 37, 268 Wechsler Adult Intelligence Scale (WAIS), 78 weight gain, 124, 130, 259 weight loss, 326 welfare, 61, 129 West Africa, 57 Western countries, 106 Western Europe, 95 white matter, 311 windows, 36, 181 wires, 326 witchcraft, 147, 316 withdrawal, 129, 211, 230, 231, 232, 238, 272, 297 witnesses, 289, 296 wood, 324 wool, 310 work activity, 7, 12 work environment, 105, 260, 283 worker rights, 106 workers, 33, 60, 64, 65, 69, 95, 99, 100, 101, 102, 105, 109, 260 Workforce Investment Act, 103, 104, 114 workplace, 50, 83, 99, 100, 102, 105, 106, 107, 113, 253, 260 World Health Organisation, 17, 18, 27, 56, 59, 124, 140, 144, 145, 162 worry, 50, 191, 264
Y yang, 324 yin, 324 young adults, 88, 189, 245, 308 young women, 124
Z
W Wales, xii, 156, 161 walking, 104, 303, 321
349
Zimbabwe, 155, 162