BUPROPION A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2003 by ICON Group International, Inc. Copyright ©2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Bupropion: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83578-0 1. Bupropion-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on bupropion. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.
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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.
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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health
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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON BUPROPION .............................................................................................. 3 Overview ....................................................................................................................................... 3 The Combined Health Information Database ................................................................................ 3 Federally Funded Research on Bupropion ................................................................................... 12 E-Journals: PubMed Central ....................................................................................................... 58 The National Library of Medicine: PubMed................................................................................ 59 CHAPTER 2. NUTRITION AND BUPROPION................................................................................... 121 Overview ................................................................................................................................... 121 Finding Nutrition Studies on Bupropion.................................................................................. 121 Federal Resources on Nutrition................................................................................................. 125 Additional Web Resources......................................................................................................... 125 CHAPTER 3. ALTERNATIVE MEDICINE AND BUPROPION ............................................................ 127 Overview ................................................................................................................................... 127 National Center for Complementary and Alternative Medicine ............................................... 127 Additional Web Resources......................................................................................................... 130 General References..................................................................................................................... 131 CHAPTER 4. DISSERTATIONS ON BUPROPION .............................................................................. 133 Overview ................................................................................................................................... 133 Dissertations on Bupropion....................................................................................................... 133 Keeping Current ........................................................................................................................ 133 CHAPTER 5. CLINICAL TRIALS AND BUPROPION ......................................................................... 135 Overview ................................................................................................................................... 135 Recent Trials on Bupropion....................................................................................................... 135 Keeping Current on Clinical Trials ........................................................................................... 140 CHAPTER 6. PATENTS ON BUPROPION ......................................................................................... 143 Overview ................................................................................................................................... 143 Patents on Bupropion ................................................................................................................ 143 Patent Applications on Bupropion ............................................................................................ 160 Keeping Current ........................................................................................................................ 165 CHAPTER 7. BOOKS ON BUPROPION ............................................................................................. 167 Overview ................................................................................................................................... 167 Chapters on Bupropion.............................................................................................................. 167 CHAPTER 8. PERIODICALS AND NEWS ON BUPROPION ............................................................... 169 Overview ................................................................................................................................... 169 News Services and Press Releases ............................................................................................. 169 Newsletter Articles .................................................................................................................... 174 Academic Periodicals covering Bupropion ................................................................................ 175 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 179 Overview ................................................................................................................................... 179 NIH Guidelines ......................................................................................................................... 179 NIH Databases .......................................................................................................................... 181 Other Commercial Databases .................................................................................................... 185 APPENDIX B. PATIENT RESOURCES .............................................................................................. 187 Overview ................................................................................................................................... 187 Patient Guideline Sources ......................................................................................................... 187 Finding Associations ................................................................................................................. 189 APPENDIX C. FINDING MEDICAL LIBRARIES ............................................................................... 191 Overview ................................................................................................................................... 191 Preparation ................................................................................................................................ 191 Finding a Local Medical Library ............................................................................................... 191
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Medical Libraries in the U.S. and Canada .................................................................................191 ONLINE GLOSSARIES ................................................................................................................197 Online Dictionary Directories ...................................................................................................197 BUPROPION DICTIONARY.......................................................................................................199 INDEX...............................................................................................................................................239
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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with bupropion is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about bupropion, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to bupropion, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on bupropion. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to bupropion, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on bupropion. The Editors
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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON BUPROPION Overview In this chapter, we will show you how to locate peer-reviewed references and studies on bupropion.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and bupropion, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “bupropion” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •
Mood Disorders in Rheumatic Disease: Evaluation and Management Source: Journal of Musculoskeletal Medicine. 16(11): 643-646,648-650. November 1999. Summary: This journal article provides health professionals with information on the diagnosis of mood disorders that commonly occur in people who have rheumatic diseases and the therapeutic strategies that may help patients better cope with the stress of chronic illness. Mood disorders are common in people who have rheumatic diseases such as fibromyalgia, rheumatoid arthritis, and systemic lupus erythematous. Altered mood tends to worsen as the illness becomes more severe. Major depression is particularly common. The presence of depressed mood, loss of interest or pleasure for 2 weeks or more, and at least five of nine established criteria such as weight change, fatigue, and indecisiveness is diagnostic. Other mood disorders that people who have a rheumatic disease may experience include minor depression, adjustment disorder with
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depressed mood, bereavement, bipolar disorder, and depressive disorder related to the general medical condition. Management includes a combination of biologic and interactive approaches. The goals of treatment are to restore normal mood, prevent suicide, and improve self esteem, productivity, and quality of life. Pharmacologic treatment of depression is an essential component of care and is usually successful. Psychopharmacologic agents include selective serotonin reuptake inhibitors, tricyclic antidepressants, monoamine inhibitors, psychostimulants, mood stabilizers, lithium, and newer agents such as bupropion. Electroconvulsive therapy is a treatment option commonly used for patients with severe, life threatening depression or psychotic depression and for patients in whom drug therapy is considered dangerous. Two major forms of psychotherapy are effective in treating patients who have major depression associated with rheumatic disease and other medical illness. Cognitive behavioral therapy deals with the relationship between cognition, affect, and behavior, whereas interpersonal therapy deals with interpersonal relationships and their effects on mood. Although many mood disorders can be managed satisfactorily within the primary care setting, referral is recommended for patients who are at significant risk for suicide or who have psychosis, psychotic depression, or full blown mania. 3 tables and 25 references. (AA-M). •
Exercise: The Healthy Alternative to Smoking Source: Diabetes Forecast. 55(5): 30-32. May 2002. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article helps readers with diabetes understand why smoking is a particularly bad habit for them. The author explains how smoking affects the blood cells, which are already under stress from the effect of diabetes and its accompanying hyperglycemia (high blood glucose levels). People with diabetes who smoke face other risks as well. Smoking increases cholesterol and blood pressure levels, and directly damages and constricts blood vessels. Smoking also limits joint mobility, which can become especially problematic if the person has long standing diabetes and is already predisposed to arthritis and other limitations in motion. The author then proposes that, as a strategy to help with quitting smoking, readers begin an exercise program. Beginning an exercise program while trying to quit smoking is a great way to replace an old addiction with a new, healthier, habit. The author also discusses the role of nicotine replacement (gum or patch) and the medication bupropion (Zyban) as other options to help with the quitting process.
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Smoking Cessation: Integrating Recent Advances Into Clinical Practice Source: Thorax. 56(7):579-582, July 2001. Summary: The author reviews the role of treatments for nicotine addiction in the management of smoking cessation and discusses how new United Kingdom smoking cessation services should best be utilized. Effective smoking cessation interventions available to physicians include (1) brief counseling, (2) intensive counseling, (3) nicotine replacement therapy (NRT), (4) bupropion, and (5) nortriptyline. There is much more evidence for NRT than for bupropion and nortriptyline. Brief antismoking advice has been shown to be effective, especially when given periodically instead of at every consultation. Intensive antismoking advice is marginally more effective than brief antismoking advice. There is strong evidence from many trials that NRT given for at least 8 weeks is an effective therapy in conjunction with advice given by physicians.
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However, NRT is only effective if used by heavier smokers, and its effect is probably maximized when behavioral support is provided. It is not known how the antidepressant bupropion works, but it decreases the withdrawal symptoms that smokers experience when quitting smoking. Two trials have indicated that nortriptyline is also effective in smoking cessation, but this antidepressant has not been licensed for use in smoking cessation in the United Kingdom. In 1999, funds were made available to develop smoking cessation services in the United Kingdom. These services are allowed to issue smokers with NRT free of charge. The author concludes with a list of four recommendations for using antismoking interventions: (1) Systematically record smoking status, (2) offer at least brief advice against smoking to motivated light smokers, (3) offer NRT to motivated heavy smokers who smoke more than 10 cigarettes daily, and (4) offer NRT and bupropion to heavy smokers who smoke more than 15 cigarettes daily. 1 table, 24 references. •
Clinician Perseverance: Helping Patients Overcoming Tobacco Dependence Source: Wisconsin Medical Journal. 100(3):14-15, 2001. Summary: The authors discuss the importance of clinician perseverance in helping patients overcoming tobacco dependence. In 1996, The Smoking Cessation Clinical Practice Guideline (AHCPR) was released. It evaluated the literature on promoting cessation and provided clinicians with strategies for helping patients interested in quitting smoking. These strategies included identification of tobacco users and offering smoking cessation at every office visit and every hospital admission for every smoker. The AHCPR was updated at the University of Wisconsin's Center for Tobacco Research and Intervention and released in 2000 as a Public Health Service Report: Treating Tobacco Use and Dependence. A key point in this report is that tobacco dependence is a chronic disease. It implies that relapse is expected for those who quit smoking. Over 70 percent of smokers have tried to quit in their lifetimes. The average smoker tries to quit four to seven times. Smokers often feel like failures and physicians trying to help them may feel like they have nothing more to offer the patient who has relapsed many times. Physicians should consider treatment of tobacco dependence in the same paradigm as treatment of other chronic conditions. Appropriate management of chronic conditions requires a collaborative effort between patient and physician. The physician must be committed to providing long-term counseling, support, and reinforcement of treatment at each visit. Physicians may also need to be prepared to refer smokers to specialists and to recommend and prescribe medication such as bupropion and nicotine replacement therapy. The author concludes that it is up to each clinician to put the Guideline into practice and persevere with patients.
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State Report: Medicaid Coverage for Tobacco-dependence Treatments Source: Health Affairs. 20(1):298-303, January-February 2001. Summary: Researchers summarize and discuss the results of a survey of states providing treatment for tobacco dependency under their Medicaid programs. The survey focused on determining whether each state's program met the Agency for Health Care Policy and Research (AHCPR) clinical practice guideline that states that Medicaid and other programs cover various aspects of nicotine replacement therapy (NRT) and counseling. A questionnaire asking about details of Medicaid coverage of tobacco dependency treatment was sent to Medicaid program directors in the 50 states and the District of Columbia (DC) in 1998. The questionnaire specifically asked about (1) which pharmacotherapy treatments were covered; (2) whether comprehensive benefits (including all forms of NRT, bupropion, and group and individual counseling) were
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offered; (3) whether the program met AHCPR guidelines; (4) other treatment interventions, such as programs for women who are pregnant or breast feeding); and (5) factors associated with treatment coverage, such as smoking prevalence. All but one state responded. Twenty-four states plus DC covered one or more treatments for tobacco dependency in their Medicaid programs. Of the states providing Medicaid coverage, 22 states and DC covered some aspect of NRT, usually the nicotine patch, gum, and/or nasal spray. Only 10 states covered any form of counseling. Six states offered comprehensive Medicaid benefits for treating tobacco dependency. Medicaid directors in 28 states and DC were aware of the AHCPR guidelines; however, only four states based their benefits on the guidelines. Only four states offered any special programs designed to assist pregnant or breast-feeding women to quit smoking. Only about one-third of the 14 states with the highest rates of smoking (at least 25 percent of the adult population smoking) provided NRT or smoking cessation counseling. States that are major growers of tobacco were less likely to provide Medicaid coverage for tobacco dependency treatments. Researchers conclude that coverage and reimbursement policies in state Medicaid programs have not kept pace with the growing evidence base for tobacco dependence treatments. Most are failing to cover services that are effective in populations that need them the most. It is in the interest of the public's health and the most efficient use of government resources for state Medicaid programs to use the existing evidence base for establishing coverage for tobacco dependency treatments. 1 table, 14 references. •
Techniques for Smoking Cessation: What Really Works? Source: Texas Medicine. 97(2):63-67, February 2001. Summary: The author discusses effective techniques for smoking cessation that can be used by primary care physicians (PCP's) to promote smoking cessation among their patients. Topics include (1) the characteristics of nicotine dependency, (2) strategies to help patients quit smoking, and (3) the stages of change of a patient contemplating stopping smoking. Brief counseling-based smoking cessation interventions (that take less than 3 minutes) offered in the context of an office or hospital visit have been shown to be effective in encouraging patients to stop smoking. These interventions are most likely to succeed when the physician correctly identifies the patient's stage of readiness to change and focuses the intervention on moving the patient toward quitting by taking one stage at a time. The author describes specific counseling strategies that can be used for the precontemplation, contemplation, and preparation stages of change. Once a patient has progressed to the preparation stage and has set a quit date, he/she becomes a good candidate for medication to treat nicotine withdrawal and craving. Medicationbased approaches include nicotine replacement therapy and bupropion. 1 figure, 16 references.
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Direct Observation of Smoking Cessation Activities in Primary Care Practice Source: Journal of Family Practice. 50(8):688-693, August 2001. Summary: Researchers investigated how often family physicians incorporated smoking cessation efforts into their patients' routine office visits and examined the effect of physician, patient, and office characteristics on the frequency of these efforts. Participants were people seen for routine office visits in 38 primary care physician practices. Researchers collected data using direct observation of physician-patient encounters, a physician survey, and an on-site examination of office systems for supporting smoking cessation. Study outcomes were the frequency of tobacco discussions among all patients, the extent of these discussions among people who were
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smokers, and the presence of tobacco-related systems and policies in physicians' offices. Data analysis indicated that physicians discussed tobacco during 633 of the 2,963 encounters with patients. Discussing tobacco was more common in the 58 percent of practices that had standard forms for recording smoking status. These discussions were also more common during new patient visits, although they occurred less often with older patients and among physicians who had been in practice more than 10 years. Of the 244 identified smokers, physicians provided assistance with smoking cessation for 39 percent. They discussed bupropion and nicotine-replacement therapy with smokers in 31 percent and 17 percent of the cases, respectively. Although 68 percent of the offices had smoking cessation materials for their patients, few recorded tobacco use in the vital signs section of the patient history or assigned smoking-related tasks to nonphysician staff. The researchers conclude that smoking cessation practices vary widely in primary care offices and they recommend strategies to help physicians incorporate systematic approaches to maximize smoking cessation rates. 1 figure, 3 tables, 29 references. •
II. Smoking Cessation in the Hospital Setting: A New Opportunity for Managed Care: Introduction Source: Tobacco Control. 9(Supplement 1):i54-i56, 2000. Summary: The author introduces a discussion of the delivery of smoking cessation interventions by managed care organizations. Although most efforts have focused on outpatient settings, smoking interventions delivered in hospitals and other sites treating patients with chronic medical illness may be particularly effective. The value of this idea has been demonstrated over the past decade. Programs designed for patients recovering from myocardial infarction have produced the best results; they have doubled the smoking cessation rate of postmyocardial infarction patients. Effective programs already share these common elements: (1) Systematic identification of smokers at or shortly after admission; (2) a bedside counseling session by a nurse or specially trained counselor, often supplemented by written or audiovisual material; (3) physician advice to stop smoking; and (4) continued contact, usually by telephone, for at least 3 months after discharge. They do not yet systematically incorporate drugs, such as nicotine replacement or bupropion, that boost smoking cessation rates in ambulatory settings. Managed care organizations need not wait to take action. Since 1996, the Agency for Health Care Policy and Research evidence-based smoking cessation clinical guidelines have clearly endorsed the concept of hospital-based smoking intervention. The challenge for managed care is to find ways to implement the elements of model intervention programs into existing health care delivery systems. 19 references.
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Office Interventions for Adolescent Smokers Source: Adolescent Medicine: State of the Art Reviews. 11(3):577-588, October 2000. Summary: The authors discuss two types of smoking cessation interventions that physicians can use in their offices with adolescents: (1) behavioral and (2) pharmacologic. Adolescent smoking behavior is influenced by different physiological and psychosocial factors, and this behavior progresses through different stages. Each stage offers an opportunity for different types of intervention. Clinicians should anticipate smoking initiation by adolescents and focus on prevention, considering every office encounter an opportunity for clinician-initiated intervention. They should ask the adolescents specific questions, using a screening smoking history to assess smoking behavior. Following initial assessments, they should provide appropriate levels of behavioral intervention. For motivated teens, pharmacologic interventions can be an important addition to behavior modification. These include nicotine replacement
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therapy (gum, transdermal patch, oral inhaler, and nasal spray) and nonnicotine replacement therapy (bupropion). Profound biochemical and physiological effects compounded by the influence of psychosocial and genetic factors make treating adolescent nicotine addiction difficult, and primary failure rates for quitting are high in adolescents. Continuing support from the primary care physician is essential. 2 figures, 6 tables, 63 references. •
Effectiveness of Interventions to Help People Stop Smoking: Findings From the Cochrane Library Source: British Medical Journal. 321(7257):355-358, August 5, 2000. Summary: Researchers summarize evidence of the effectiveness of available smoking interventions, based on findings from the Cochrane Tobacco Addiction Review group. The group identifies and summarizes evidence of interventions to reduce and prevent tobacco use, creating and maintaining systematic reviews to inform clinicians, policymakers, and people who want to quit smoking. Summary points include: (1) advice given by doctors, structured interventions by nurses, and individual and group counseling are effective forms of intervention; (2) generic self-help materials are no more useful than brief advice but more effective than doing nothing, and personalized materials are more effective than are standard materials; (3) anxiolytics and lobeline are ineffective; (4) all forms of nicotine replacement therapy are effective; (5) the antidepressants nortriptyline and bupropion increase cessation rates in a small number of trials, although the usefulness of the antihypertensive drug clonidine is limited by side effects; and (6) the effectiveness of aversion therapy, acupuncture, mecamylamine, hypnotherapy, and exercise is uncertain. 27 references.
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Promoting Cessation of Tobacco Use Source: Physician and Sportsmedicine. 28(12):59-60, December 2000. Summary: Tobacco causes over 450,000 deaths yearly, and although adults smoking rates have decreased in the past 2 decades, the decline has leveled off recently, and youth tobacco use is increasing. The recently released Public Health Service Clinical Practice Guideline, entitled Treating Tobacco Use and Dependence, contains evidencebased information about behavioral counseling; first-line pharmacologic therapies (e.g., nicotine-delivered agents and sustained release bupropion hydrochloride); and secondline pharmacologic therapies (e.g., clonidine hydrochloride and nortriptyline hydrochloride). Since most tobacco users see health care professionals each year, a first step to effective care is systematic institutional identification and tracking of these people. Tobacco dependence should be considered a chronic disease. Effective treatments are available, and clinicians should treat their patients through periods of relapse and remission. Every patient who uses tobacco should be offered an effective treatment. Even brief consultation at every clinic visit is a significant step toward improving abstinence rates. The guide offers various brief interventions for treating patients according to their smoking status. Relapse prevention counseling is important and should include congratulations for success, encouragement of patient problem solving, and identification of specific problems that threaten abstinence. 4 references.
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Smoking Cessation Guidelines for Health Professionals: An Update Source: Thorax. 55(12):987-999, 2000. Summary: The authors update the evidence base and key recommendations of the Health Education Authority smoking cessation guidelines for health professionals
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published in 1998. This update used current Cochrane reviews as well as individual studies. It presents additional detail about the effectiveness of interventions and comments on issues related to implementation. Recommendations include clarification of important ideas addressed only in general terms in the original guidelines. This update concludes that smoking cessation interventions delivered via the National Health Service are a very cost-effective method of preserving life and reducing ill health. The strategy that the guidelines recommend involves the following: (1) General practitioners should opportunistically advise smokers to quit during routine consultations, giving advice on and/or prescribing effective medications to help them and referring them to specialist cessation services; (2) specialist smokers' services providing behavioral support for smokers who want help stopping, as well as effective medications, should be provided; (3) specialist cessation counselors should provide behavior support for people in hospitals and pregnant smokers who want to quit; and (4) all health professionals involved in smoking cessation should encourage and assist smokers in the use of nicotine replacement therapies or bupropion. The key recommendations of the 1998 guidelines are reinforced. New key features of this update include (1) clarification of what primary health care teams can be expected to undertake, (2) the recommendation that smokers be referred to specialist smokers' clinics, (3) a key distinction between behavioral support provided by trained smoking cessation specialists and more limited support provided by other health professionals as part of routine care, (4) recommendations concerning bupropion, and (5) the recommendation that hospitals be smoke-free and this policy be strictly enforced. 1 table, 70 references. •
Smoking Cessation in Primary Care Source: Indiana Medicine. 89(2):165-168, March-April 1996. Summary: A smoking cessation specialist outlines three areas in which health care professionals can play an important role: (1) The medical setting, (2) office-based interventions, and (3) pharmacologic therapy. With regard to the medical setting, health care professionals should ensure that offices and hospitals are smoke-free, reduce the exposure of their patients to the advertising and promotion of tobacco products by subscribing to magazines that do not contain any tobacco advertising, and not focus their attention on abstinence as the only outcome. Although abstinence is the ultimate goal, movement through the stages of change; i.e., precontemplation, contemplation, preparation, action, and maintenance, is an important outcome in itself. Persons in the preparation stage of readiness are twice as likely to stop smoking on the next attempt compared to those who are in the contemplation stage at the time of the initial intervention. The National Cancer Institute has developed an office-based intervention for physicians and other health professionals that provides brief but effective intervention. It is based on the four A's: (1) Ask all patients about their smoking behavior, (2) advise every smoker to stop smoking, (3) assist every smoker in setting a quit date, and (4) arrange a followup visit. Pharmacological therapy offers a useful adjunct to smokers who are trying to stop smoking. Although nicotine gum has recently been overshadowed by the introduction of nicotine patches, it still has a role to play in smoking cessation and is effective when used properly. After initiating nicotine patch therapy on the stop date, the patient should have a followup physician visit within the first 2 weeks. For those who have not stopped smoking at 4 weeks while using the patch, the author recommends that the patch be discontinued and the patient encouraged to establish a new quit date in the near future. Patients with a high degree of nicotine dependence may need a more intensive program such as a group intervention or an inpatient treatment program where patients are hospitalized to initiate abstinence. Pharmacologic agents under investigation include nicotine nasal
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spray and bupropion. The author concludes by saying that the physician plays a key role in helping patients stop smoking. 20 references. •
Should the Use of Smoking Cessation Products Be Promoted by Dental Offices?: An Evidence-Based Report Source: Journal of the Canadian Dental Association. 67(3): 149. March 2001. Contact: Available from Canadian Dental Association. 1815 Alta Vista Drive, Ottowa, ON K1G 3Y6. (613) 523-1770. E-mail:
[email protected]. Website: www.cda-adc.ca. Summary: This article reports on a study undertaken to address the issue of whether dentists should promote the use of smoking cessation products. In the study, an evidence based methodology was applied to find answers to three questions: Does tobacco use affect periodontal health? Are dentists effective cessation counselors? Do smoking cessation products improve the effectiveness of cessation intervention? The author searched MEDLINE and undertook manual searches, uncovering relevant evidence to use in developing evidence based recommendations. There is fair evidence that tobacco use is a major factor in the progression and treatment outcome of adult periodontitis and that quitting tobacco use is beneficial to periodontal health. There is good evidence to recommend that oral health professionals provide cessation counseling. Quit rates are nearly doubled when cessation services are offered. There is good evidence to recommend the use of smoking cessation adjuncts, including transdermal nicotine and nicotine gum, as well as bupropion (an antidepressive drug that has shown some effectiveness in smoking cessation). The author concludes that in view of the strong supporting evidence, dental offices should incorporate systematic smoking cessation services into routine patient care and should promote the use of proven cessation products by patients who are attempting to quit. 2 tables. 54 references.
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Treatment of Nicotine Addiction Source: Texas Dental Journal. 117(6): 26-32. June 2000. Contact: Available from Texas Dental Association. 1946 South Interregional Highway, Austin, TX 78704-3698. (512) 443-3675. Website: www.tda.org. Summary: This article outlines strategies for dentists to use when helping patients address a nicotine addiction. The authors note that people begin using tobacco for sociocultural reasons, but the social stimuli are quickly surpassed in influence by internal drug seeking and drug using behavior. Cessation strategies that stress only behavioral interventions and do not deal with the patient's physical nicotine dependence address only part of the problem. The authors note that a systematic and caring approach that includes education, behavioral counseling, and psychological support together with pharmacotherapy results in significantly higher abstinence rates. The authors review various cessation strategies, including the Four A's (Ask, Advise, Assist, Arrange), drug therapies, nicotine gum, transdermal nicotine patches, nicotine nasal spray, nicotine inhalation system, bupropion HCl (Zyban), weight control programs, and diet therapy. The authors conclude that the combination of pharmacotherapy and behavioral interventions, even on a minimal level, have been shown to be effective in cessation. Such strategies are certainly highly cost effective, given the enormous costs to society of smoking related illnesses. One chart summarizes the FDA approved aids used in nicotine cessation. 2 figures. 23 references.
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Pharmacotherapy of Smoking Cessation Source: Archives of Family Medicine. 9(3):270-281, March 2000. Summary: The authors reviewed data on the efficacy of approved medications, benefits, adverse effects, and appropriate use of these products in smoking cessation. They also discuss nicotine addiction and treatment for special populations. Most smokers want to quit, but their quit attempts are usually unsuccessful because of their addiction to nicotine. The Agency for Health Care Policy and Research (AHCPR) published its Smoking Cessation Clinical Practice Guideline recommending a 5-step approach to be used by primary care physicians: (1) Ask, (2) advise, (3) assess, (4) assist, and (5) arrange. Pharmacological treatment for smoking cessation includes (1) nicotine replacement therapy (NRT), including nicotine polacrilex gum, transdermal nicotine patches, nicotine nasal sprays, and nicotine inhalers; (2) nonnicotine drugs, including bupropion, an aminoketone with doperminergic and adrenergic actions; and (3) combination drug therapy, including combined use of NRT products and combined use of the transdermal patch and bupropion. The AHCPR recommends that clinicians offer minorities the same smoking cessation treatments proven to be effective for the general population. Behavioral therapy has been shown to be effective and should be encouraged for helping pregnant women quit smoking. If this is not effective, NRT methods should be considered since they deliver lower levels of nicotine than smoking. Physicians should adopt a more aggressive approach to encouraging smoking cessation among patients with cardiovascular and lung disease, including combination drug therapy since these patients are likely to be more nicotine dependent. Physicians should be aware that relapse is common among smokers during and after smoking cessation treatment. The authors concluded that recent increases in approved pharmacological options for smoking cessation provides primary care physicians with a wide range of treatment approaches. 1 figure, 3 tables, 96 references.
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Smoking and Women's Health Source: International Journal of Gynecology and Obstetrics. 70(1):159-163, July 2000. Summary: The author discusses the role of the obstetrician/gynecologist in reducing morbidity and mortality from cigarette smoking by (1) educating women about the dangers, (2) advising them not to smoke, and (3) assisting those who do smoke to quit. Education is needed regarding both the reproductive and non-reproductive health issues of tobacco use. Smoking among women is associated with an increased risk of cancer, coronary artery disease, bronchitis, emphysema, peripheral vascular disease, cerebrovascular disease, and gastric ulcers. Smoking also affects many aspects of reproductive health, including fertility, menstrual function, and contraceptive options. In the United States, the National Cancer Institute recommended a program of clinical interventions (four A's), and has encouraged all physicians and other health care professionals to incorporate them into their practices with the goal of reducing the number of smokers. The four A's are (1) ask all patients if they smoke, (2) advise those who do smoke to stop, (3) assist smokers in their efforts to quit, and (4) arrange followup to review the patient's progress. There is evidence from clinical trials that the use of nicotine replacement or bupropion will improve smoking cessation rates. There are also nicotine gums, transdermal patches, inhalers, and nasal sprays available. There is some evidence that using both bupropion and the nicotine patch may be even more effective than using either agent alone. 12 references.
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Smoking and Women's Health: Opportunities to Reduce the Burden of Smoking During Pregnancy Source: Canadian Medical Association Journal. 163(3):288-289, August 8, 2000. Summary: The authors discuss the role of clinicians in smoking cessation in pregnant women. The need to assess the smoking habits of each woman during each contact with a clinician is clear. Clinicians who provide health care to women have an important role to play in reducing the burden of smoking among women. Studies indicate that brief cessation counseling for 5 to 15 minutes when delivered by a trained provider with pregnancy-specific self-help materials significantly increase rates of cessation among pregnant smokers. Five specific steps toward cessation (Ask, Advise, Assess, Assist, and Arrange) and recommended providers are outlined in a one-page form, Brief Smoking Cessation Counseling for Pregnant Patients. Efforts to prevent tobacco exposure should begin before conception since more than 50 percent of women do not recognize that they are pregnant until after the fourth week of gestation. Pregnant women who smoke most heavily do not appear to respond to behavioral interventions. The use of pharmacologic approaches to achieve smoking cessation in women who are unable to stop smoking, including nicotine replacement therapy, nonnicotine products, such as bupropion hydrochloride, and second-line pharmacotherapies, such as clonidine and nortriptyline, has been suggested; but the safety of these approaches during pregnancy is not well documented. Long-term reduction in tobacco exposure during pregnancy can be achieved only by encouraging teenage girls and young women not to start smoking. 10 references.
Federally Funded Research on Bupropion The U.S. Government supports a variety of research studies relating to bupropion. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to bupropion. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore bupropion. The following is typical of the type of information found when searching the CRISP database for bupropion: •
Project Title: A CLINICAL TRIAL OF TWO MEDICATIONS ON SMOKING CESSATION Principal Investigator & Institution: Johnson, Karen C.; Associate Professor of Medicine; Preventive Medicine; University of Tennessee Health Sci Ctr Health Science Center Memphis, TN 38163
2 Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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Timing: Fiscal Year 2002; Project Start 07-JAN-2002; Project End 31-DEC-2006 Summary: (provided by applicant): Cigarette smoking poses a serious but preventable health risk. Even though the detrimental effects of smoking are well known, the prevalence of cigarette smoking remains high in the U.S., particularly for younger persons, persons of lower socioeconomic status, and minority groups. Although some persons quit smoking on their own or with the help of behavioral smoking cessation interventions, there are a substantial number of smokers who are unable to quit smoking or relapse to smoking without the aid of pharmacologic therapy for smoking cessation. Currently, there are two types of pharmacologic therapies (Nicotine Replacement Therapy and Sustained-release bupropion) that are FDA approved for smoking cessation in the U.S. To date, there has been no clinical trial comparing use of the nicotine patch and sustained-release bupropion, alone or in combination, as pharmacologic therapy for smoking cessation among low income, younger participants or in minority participants. Given the high relapse rates among these groups in general, the combination of nicotine replacement therapy and sustained-release bupropion may be particularly efficacious. Therefore, we hypothesize that use of a combination of the nicotine patch and sustained-release bupropion as compared to use of the nicotine patch alone or to sustained-release bupropion alone will result in increased initial and long term rates of smoking cessation in younger low income and minority persons who smoke. We plan to test these hypotheses in this double blind clinical trial by randomizing younger, low income and minority persons who smoke to one of three groups: Group 1) Nicotine patch plus placebo sustained-release bupropion, Group 2) Sustained-release bupropion plus placebo nicotine patch, or Group 3) Nicotine patch plus sustained-release bupropion. Our primary endpoint assessment is smoking cessation rates by self-report verified by biochemical validation at different time points between the three treatment groups. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIDEPRESSANT TREATMENT FOR DEPRESSED COCAINE DEPENDENT PATIENTS Principal Investigator & Institution: Oliveto, Alison H.; Research Scientist; Yale University 47 College Street, Suite 203 New Haven, CT 065208047 Timing: Fiscal Year 2001 Summary: Preliminary data with two antidepressants, bupropion and sertraline, suggest a common mechanism for treating cocaine dependent patients, particularly those with concurrent depression. In addition to other mechanisms of action, these two share dopamine reuptake inhibition which may be important, not only due to the important role that dopamine plays in cocaine induced reinforcement, but also because the doparnine reuptake carrier can be upregulated in many cocaine patients. This upregulation may respond to renormalization using a weak blocker of the dopamine transporter when patients are cocaine-free and craving. Thus, the aim of this proposal is to examine the clinical efficacy of bupropion vs. placebo (years I3) as well as sertraline vs. placebo (years 3-5) in currently abstinent, depressed cocaine-dependent volunteers. We will also pilot the use of a pharmacological augmentation strategy for nonresponders to the initial trial with sertraline. Each I2-wk, double blind, randomized clinical trial will provide treatment for 60 depressed cocaine-dependent individuals (1865 yrs). Participants first will be placed in research beds on the Quarterway House at the VA CT Healthcare System to initiate initial cocaine abstinence. Subjects will be randomly assigned to receive either active medication (i.e., 300 mg/day of bupropion in study I and 200 mg/day of sertraline in study 2) or placebo. At the end of week 2,
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depressive symptoms severity will be redetermined and used as a stratifying factor in subsequent analyses. Then participants transfer to the Outpatient Treatment Research Program, where they continue to receive active medication or placebo and participate in weekly individual cognitive behavioral therapy for weeks 3-12. During weeks 3-12, participants can earn monetary incentives for attending scheduled visits and returning take-home medication bottles. During the pharmacological augmentation portion of the sertraline trial, nonresponders continue to receive the placebo or sertraline under blinded conditions and openly receive bupropion (50 mg/day) as they continue to participate in cognitive behavioral therapy during weeks 13-16. Efficacy will be determined by length of time in treatment, length of time to relapse by self-report and urine toxicology, depressive symptom severity and psychosocial functioning. Depressive symptom severity as a prognostic factor in treatment response will be examined. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ASSESSING AND UNDERSTANDING TOBACCO DEPENDENCE Principal Investigator & Institution: Fiore, Michael C.; University of Wisconsin Madison 750 University Ave Madison, WI 53706 Timing: Fiscal Year 2001 Summary: (Applicant's Description) Why is relapse far and away the most likely outcome of a cessation attempt? It is difficult to imagine answers to this question that do not implicate tobacco dependence. Dependence is the conceptual nexus integrating the surface features of addiction (e.g., heavy use, severe withdrawal, tendency to relapse, etc.). Greater understanding of the construct linking those phenomena should foster more rapid progress in developing effective treatments. The overarching goal of this research is to develop improved dependence- assessment instruments through theoretical scale construction that focuses on hypothesized mechanisms underlying dependence, rather than on surface manifestations (e.g., cigarettes per day, whether one inhales). Once initial scales are constructed, they will be subjected to diverse validity assessments. Two studies are proposed. In Study I, 460 smokers will be recruited such that they reflect a broad range of dependence. All will participate in a cessation trial with random assignment to 2 or 4 mg nicotine gum or placebo. Three theory-based constructs will serve as chief criteria for the selection of Subscale on the Dependence Questionnaire (DQ): withdrawal severity, pre-cessation smoking heaviness, and relapse. These will be assessed with multiple, sensitive indices. For example, assessments of withdrawal will include measures of both symptom elevation and symptom trajectory. Moreover, over the first five days of cessation, intensive assessment of symptoms will occur via computerized telephone interview. Two additional measures will be gathered because of their strong motivational links to dependence. Genetic markers related to dopaminergic structures and activities will be assessed in all 460 subjects. In addition, a subsample of placebo subjects (N=60) will participate in a behavioral economic assessment, allowing examination of elasticity as a dependence index and providing a further criterion against which to test the DQ. Study 2 (N=400) will employ the same design with two exceptions. First, the study will not involve the elasticity assessment. Second, the active smoking cessation pharmacotherapy will be changed to bupropion so that the stability of the factor structure and predictive validity of the DQ can be determined in a systematic replication. The validity data will address both vital clinical as well as theoretically significant criteria. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BIOBEHAVIORAL LUNG CANCER PREVENTION PROGRAM Principal Investigator & Institution: Lerman, Caryn E.; Professor of Psychology in Psychiatry; V T Lombardi Cancer Res Center; Georgetown University Washington, DC 20057 Timing: Fiscal Year 2001; Project Start 10-SEP-1993; Project End 30-JUN-2001 Summary: ABSTRACT=In our original grant (R01CA63562), we evaluated the impact of a smoking cessation treatment which incorporated motivational feedback about genetic susceptibility to lung cancer. We found strong positive effects of genetic feedback on perceived risk, perceived quitting benefits, and fear arousal. While smokers receiving genetic feedback made more quit attempts, they were no more likely to quit than were smokers receiving standard minimal contact cessation treatment. Observing that the vast majority of smokers were unable to quit, even in the face of perceived vulnerability and heightened motivation, we became interested in the genetic basis of nicotine dependence and smoking cessation. The strongest evidence (by our group and others) supports the role of the dopamine transporter gene (SLC6A3) which regulates reuptake of dopamine at the synapse. This is consistent with a large body of data suggesting that the reinforcing effects of nicotine are due to its impact on the neurotransmitter dopamine. Thus, in this competitive renewal, we propose to extend our research by evaluating the role of SLC6A3 in the response of smokers to pharmacological smoking cessation treatment (bupropion/Zyban). We have selected bupropion because: (a) initial data from randomized clinical trials provide strong support for its efficacy as a smoking cessation treatment, and (b) bupropion has inhibitory effects of dopamine transport (the protein product of the SLC6A3 gene). The specific aims of the proposed research are: (1) to evaluate the role of genetic factors in response to standard smoking cessation treatment; (2) to evaluate the role of genetic factors in response to bupropion treatment; and (3) to evaluate the psychobiological mechanisms by which genotype and bupropion influence smoking cessation. The study will be a double blind randomized placebocontrolled clinical trial of bupropion in 600 adult male and female smokers. The factorial design includes one treatment factor (bupropion plus standard treatment (with nicotine patch) vs. placebo plus standard treatment with patch) and one subject factor (SLC6A3 genotype, genetically predisposed vs. genetically protected). Bupropion or placebo will be delivered over a 10-week treatment period. All subjects will receive standard minimal contact cessation treatment, which includes two in-person sessions plus five brief structured phone-counseling sessions. A major innovation of this study is that we will use a behavioral economics computer paradigm to evaluate the reinforcing value of nicotine at pre-treatment and during bupropion therapy. Other mediating outcomes (mood, withdrawal) will be assessed at pre-treatment and at multiple points during treatment. The primary smoking cessation outcomes will be assessed at 1-, 6and 12- months post-treatment. The proposed research will be the first to examine the role of specific genetic factors in response to pharmacological therapy for smoking cessation and to evaluate novel mediating mechanisms. The long-term objective is to provide information necessary to match smoking cessation treatments to individuals, based on their genetic predispositions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BODY IMAGE TREATMENT FOR WEIGHT CONCERNED SMOKERS Principal Investigator & Institution: Clark, Matthew M.; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2003
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Summary: (provided by applicant): This application will serve as the foundation on which the Principal Investigator will build a major line of research dedicated to the area of improving smoking abstinence rates in weight-concerned smokers. Many individuals smoke to manage their weight. This subpopulation of smokers has been classified as having weight concerns. Weight concerned smokers have lower smoking abstinence rates compared to non-weight concerned smokers, and women have higher rates of weight concern than men. Behavioral weight management interventions added to nicotine dependence treatment have not been found to be effective and pharmacological interventions have delayed rather than prevented weight gain. New avenues need to be explored for this difficult-to-treat subpopulation. A novel approach is to focus on changing the weight concerns themselves by implementing a body image intervention. Negative body image has been found to predict reduced rates of smoking abstinence. The primary aim of this study is to evaluate the efficacy of body image treatment compared to weight management intervention on improving the smoking abstinence rates in weight concerned smokers after 12 weeks of treatment and at 6-month (week 24) follow-up. A further aim is to examine the effect of body image treatment on improving body image satisfaction, and reducing weight concerns in weight concerned smokers. We hypothesize that the body image treatment will be associated with higher 7-day point-prevalence smoking abstinence rates, greater improvements in body image satisfaction scores, and decreased weight concerns at end of treatment (week 12) and at 6-month follow-up as compared to the weight management intervention. The ultimate goal is to develop effective interventions that will reduce tobacco-related morbidity and mortality in this population. This is consistent with the objectives of the National Cancer Institute to develop and test new behavioral, pharmacological, and combination therapies to treat nicotine dependence, with special emphasis on populations at high risk. Subjects will be randomly assigned to either a 12-week group cognitive-behavioral treatment for body image improvement (experimental group) (N=20) or to a 12-week group behavioral weight management treatment (contact control group) (N=20). Subjects in both conditions will receive bupropion and prescription for home-based exercise. The major assessments will occur at end-of-treatment (week 12) and at 6-month (week 24) follow-up. Dependent measures include 7-day point prevalence smoking abstinence confirmed with expired air carbon monoxide, and self-report measures of body image satisfaction and weight concerns. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BUPROPION AND BEHAVIORAL TREATMENT FOR YOUNGER SMOKERS Principal Investigator & Institution: Hurt, Richard D.; Professor of Medicine; Mayo Clinic Rochester 200 1St St Sw Rochester, MN 55905 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-MAY-2004 Summary: (adapted from investigator's abstract): The primary aims of this study are: (1) to evaluate the efficacy of a 12-week course of sustained release buproprion (300mg/d) compared to placebo on end of treatment and 1-year abstinence rates, (2) to evaluate the efficacy of brief office intervention with parental support compared to minimal intervention on the end of treatment and 1-year abstinence rates, and (3) to determine if the combination of buproprion with brief office intervention with parental support is more effective than placebo and minimal intervention. The primary hypotheses to be tested are: (1) a 12-week course of buproprion will increase the end of treatment and 1year smoking abstinence rates, compared to placebo, and (2) smoking abstinence rates at the end of treatment and 1-year will be increased with brief office intervention with
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parental support, compared to minimal intervention. The ultimate goal of this work is to develop effective interventions, which will reduce the risk of tobacco-related morbidity and mortality in these younger smokers. The investigator proposes to test these hypotheses and accomplish these aims by providing 616 adolescent cigarette smokers aged 13-17 with buproprion or placebo for 12 weeks combined with minimal intervention or brief office intervention with parental support, in a 4-group, randomized double blind design. The four groups will be: (1) placebo buproprion, minimal intervention, (2) placebo buproprion, brief office intervention with parental support, (3) active buproprion, minimal intervention, and (4) active buproprion, brief office intervention with parental support. Primary assessments will be point prevalence smoking abstinence rates at end of treatment (week 12) and at 52 weeks. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CESSATION
BUPROPION
AND
WEIGHT
CONTROL
FOR
SMOKING
Principal Investigator & Institution: Marcus, Marsha D.; Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2001; Project Start 01-JUL-1986; Project End 30-NOV-2004 Summary: Although rates of smoking have declined, the decrease in prevalence has been much less pronounced in women than in men, and women are particularly vulnerable to ongoing smoking-related morbidity and mortality. One reason for gender differences in smoking cessation is concern about cessation-related weight gain among women. In the previous grant period, we tested the efficacy of two adjuncts to a standard cessation program for weight concerned women, behavioral weight control (WEIGHT) and cognitive behavior therapy to reduce weight concerns (CBT). Results of this trial have shown that CBT is a promising adjunctive treatment for weight concerned women. Specifically, 59.7% of known in the CBT condition were abstinent from smoking in post- treatment. Further, CBT yielded significantly higher abstinence rates in 3month follow-up when compared to standard cessation only or the WEIGHT adjunct, with cessation rates of 39.4%, 23.6%, and 22.6% for the three groups, respectively. Nevertheless, abstinence rates decreased significantly during follow-up for all groups, and in the present study, we propose a randomized, double-blind, controlled trial to determine whether the addition of buproprion (Zyban) to CBT treatment for weightconcerned women will enhance longer-term abstinence. Four hundred fifty weightconcerned women smokers will be randomized to either cognitive behavioral treatment for weight concerns plus standard cessation (CBT) or standard smoking cessation only (STANDARD), and six months of either buproprion (Zyban) or placebo. Primary outcome will be rates of smoking abstinence and time to relapse across the four treatment conditions. In addition, we will determine the effects of these treatments on tobacco withdrawal, mood, and weight. Results of this investigation will provide information on the relative efficacy of CBT and buproprion alone and in combination, and the utility of drug and counseling strategies that are specifically tailored for a highrisk population. This is a competing continuation of 2-R01-DA04174-13. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BUPROPION AS A SMOKING CESSATION AID IN ALCOHOLICS Principal Investigator & Institution: Grant, Kathleen M.; U.S. Dept/Vets Affairs Med Ctr(Omaha) Affairs Medical Center Omaha, NE 68105 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2004
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Summary: (provided by applicant): Objectives: The purpose of the current proposal is to test the use of sustained release bupropion in patients in treatment for alcohol abuse/dependence as an aid for smoking cessation. It is our overall hypothesis that cigarette smoking cessation can be achieved in patients during treatment for alcohol abuse/addiction, particularly if treatment is tailored. Our proposed work will address the following four specific aims: Aim one will assess whether the use of sustained release bupropion as a smoking cessation alters abstinence from cigarette smoking for patients with alcohol abuse/dependence in an alcohol treatment program. Aim two will assess whether the use of sustained release bupropion as a smoking cessation aid alters sobriety from alcohol in patients. Aim three will assess the incidence of side effects of sustained release bupropion when used as a smoking cessation aid for patients with alcohol abuse or dependence in an alcohol treatment program. Aim four will assess the adherence to the medication regimen between the two groups. Research Design and Methodology: We propose to use a randomized, double blind, placebo controlled clinical trial to test the safety and efficacy of the addition of a nine-week course of sustained release bupropion for cigarette smoking cessation in a VA SATC and a community-based alcohol treatment program. 200 total patients will be enrolled. Patients meeting study criteria will be randomized to receive either sustained released bupropion or placebo. Both groups will receive nicotine replacement therapy. Participants will be followed for 6 months. A repeated measure design will be used to compare outcome measures of smoking cessation and sobriety from alcohol in two groups (control, intervention) at baseline, 4 weeks, 9 weeks, and 6 months. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BUPROPION AS AN ADJUNCT TO THE NICOTINE PATCH PLUS CBT Principal Investigator & Institution: Fava, Maurizio; Director, Depression Clinical & Res. Pro; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2001; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: We are proposing a five-year, double-blind, placebo-controlled trial on the smoking cessation efficacy of bupropion as an adjunct to the standard combination of group cognitive-behavioral therapy (CBT) plus nicotine replacement. Our primary aims are 1) to examine the additional benefit of adding the antidepressant bupropion to a standard treatment for smoking cessation of CBT and nicotine replacement among smokers who have a history of either current or past unipolar depressive disorders (major depressive disorder, dysthymia, and minor depression), and 2) to determine, if bupropion indeed improves in this population a smoker's odds of quitting, whether its effect is achieved mainly through its impact on the negative mood states associated with depression. In order to provide a powerful test of both hypotheses, this study will enroll only smokers with a history of either current or past unipolar depressive disorders. In addition, allowing the inclusion of patients with a history of unipolar depressive disorders makes the proposed study more clinically relevant and its findings more generalizable, as several studies suggest that, as the prevalence of smoking continues to diminish in the general population, an increasing percentage of those who remain smokers are patients with psychiatric illnesses, especially depression. We expect that the efficacy of the standard combination of group CBT plus nicotine replacement will be greatly enhanced by the addition of bupropion in all smokers, but that the addition of bupropion will be especially helpful to those smokers who currently suffer from clinically significant depressive symptoms. The study involves the enrollment over 48 months of 300 individuals. We predict that 50 percent of the enrolled patients will meet
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criteria for current unipolar depressive disorders. After the 12-week acute treatment phase, patients will be followed for 12 months. The study design therefore involves the random assignment of current or past history of unipolar depressed patients to two treatment conditions: 1) group CBT plus nicotine patch plus bupropion (current depressive disorder bupropion group, estimated n=75; past depressive disorder bupropion group, estimated n=75); 2) group CBT plus nicotine patch plus placebo (current depressive disorder placebo group, estimated n=75; past depressive disorder placebo group, estimated n=75). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BUPROPION FOR HOSPITALIZED SMOKERS W CORONARY DISEASE Principal Investigator & Institution: Rigotti, Nancy A.; Massachusetts General Hospital 55 Fruit St Boston, MA 02114 Timing: Fiscal Year 2001; Project Start 20-MAR-1999; Project End 28-FEB-2003 Summary: Over 2 million Americans are hospitalized annually with a myocardial infarction (MI) or unstable angina pectoris, two acute, potentially fatal manifestations of coronary heart disease (CHD) that are responsible for substantial morbidity, mortality, and health care costs. Smoking cessation is highly cost-effective and universally recommended for the approximately 20 percent of these patients who smoke. Hospitalization for acute CHD is an excellent time to initiate smoking cessation because it requires temporary tobacco abstinence at the same time that illness increases smokers' motivation to quit. However, at least 40 percent of smokers fail to quit even with the most effective current treatment, cognitive-behavioral counseling that begins in the hospital and continues after discharge. More powerful intervention strategies are clearly needed. Adding pharmacotherapy to counseling, which is standard practice in outpatients, is a new approach that has not been tested in this setting. Concern about the safety of nicotine replacement in MI patients limits its use. A non-nicotine antidepressant, sustained-release (SR) bupropion (Zyban, Wellbutrin SR), has demonstrated efficacy for smoking cessation and was recently FDA- approved for this use. Bupropion appears to be safe in cardiac patients and may have the additional benefit of preventing post-MI depression, an independent predictor of mortality. We propose to test the efficacy and safety of this novel treatment, bupropion SR, for smoking cessation in adult smokers hospitalized with acute CHD. We have designed a randomized, double-blind, placebo-controlled trial to determine whether bupropion SR, initiated in the hospital and continued for 12 weeks, is effective and safe when added to a previously-tested nurse-delivered cognitive-behavioral smoking counseling intervention that begins in the hospital and continues by telephone contact after discharge. Outcomes will be assessed at hospital discharge and 1, 3, and 12 months after the start of treatment. The primary outcome measure is biochemically-confirmed 7-day point prevalence tobacco abstinence at 1 year follow-up. Secondary objectives are to test whether bupropion SR delays the time to smoking relapse; increases the smoking cessation rate at the end of treatment (3-months); and reduces CHD morbidity and depressive symptoms and improves health-related quality of life over 1 year. If found to be safe and effective, bupropion SR could become a standard part of "secondary prevention" therapy for smokers with acute CHD, a large, high-risk, high-cost patient group. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BUPROPION FOR SMOKING CESSATION IN PREGNANCY Principal Investigator & Institution: Miller, Hugh S.; Obstetrics and Gynecology; University of Arizona P O Box 3308 Tucson, AZ 857223308 Timing: Fiscal Year 2002; Project Start 05-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): Smoking in pregnancy is associated with a variety of complications, including low birth weight (LBW), intrauterine growth restriction (IUGR), antenatal bleeding and pre-term birth (PTB). These significant health hazards could largely be prevented with successful antepartum smoking cessation. In recognizing both the success and the limitations of counseling based smoking cessation programs, we are interested in piloting the use of pharmacologic agents for reduced smoking during pregnancy. The first objective of the proposed research is to evaluate the efficacy of a pharmacologic aid for successful smoking cessation in pregnancy. The specific aims include evaluating bupropion SR's efficacy for both cessation and reduction of antenatal smoking by comparing pregnant women receiving smoking cessation counseling combined with placebo to those pregnant women who receive smoking cessation counseling combined with bupropion SR. The second objective of the proposed research is to evaluate the safety of bupropion SR used for smoking cessation in pregnancy. The specific aims include determining the adverse events and adverse effects associated with antenatal bupropion administration. Secondarily, the pilot seeks to evaluate the impact of bupropion SR on maternal well being, anxiety, depression, psychosocial variables and neonatal outcome (birth weight, Apgar scores, and neonatal intensive care unit admission rate). This research will consist of a pilot double blind placebo controlled randomized trial in which pregnant women who self-report continued smoking at the inception of prenatal care, will be randomized to one of two groups. The interventions will consist of brief smoking cessation counseling in combination with either placebo or bupropion SR. Participants will be surveyed to determine important demographic factors, psychosocial variables, and intercurrent medical illnesses, including measures of psychiatric disease, particularly concurrent depression. Maternal outcome measures will include cessation and smoking reduction rates by self-report and biochemical analysis (urinary cotinine and breath carbon monoxide analysis). The proposed research seeks to evaluate whether a pharmacologic aid (bupropion SR) administered antenatally can achieve higher rates of smoking cessation and smoking reduction without imposing serious adverse outcome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BUPROPION IN ADOLESCENTS WITH COMORBID ADHD & DEPRESSION Principal Investigator & Institution: Daviss, William B.; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, PA 15260 Timing: Fiscal Year 2003; Project Start 06-DEC-2002; Project End 30-NOV-2007 Summary: (provided by applicant): Attention deficit hyperactivity disorders (ADHD) in youth occur comorbidly with other psychiatric conditions approximately two thirds of the time. Major depressive disorder and dysthymic depression are common, occurring in as many as 40% of youth with ADHD. The comorbid occurrence of ADHD and depression (ADHD + Dep) may cause substantial long-term morbidity. While psychopharmacology is widely used to treat juvenile ADHD and/or depression, no research has established an efficacious treatment for ADHD + Dep, or for most other comorbid ADHD disorders. This five year Mentored Patient-Oriented Research Career Development Award (RCDA) will provide the candidate, a board certified child and
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adolescent psychiatrist, training to undertake pharmacological trials of youth with ADHD and comorbid disorders. The candidate has had extensive previous clinical experience and some research experience in the pharmacological treatment of juvenile ADHD + Dep. The RCDA will provide the candidate formal training in pharmacology, clinical trial design, and statistical analyses as well as the empirical assessment of juvenile ADHD, depression, and other comorbid psychopathology. The candidate will also receive training in ethical issues germane to juvenile psychopharmacology studies. Training will occur through a combination of formal coursework, guided readings, and consultation with mentors having relevant expertise. This training will be applied in a pharmacologic study of adolescents with ADHD and depression (major depression, dysthymia). The protocol will consist of a 2-week washout/observational period, then an 8-week randomized, placebo-controlled trial (RCT) to determine the efficacy of bupropion SR. Then a 24-week open label continuation phase will be used to determine if treatment response and tolerability persist. Exploratory analyses will assess correlations of initial treatment response with both pharmacological variables (plasma levels of bupropion and its metabolites; noradrenergic and dopaminergic effects as estimated by reuptake blockade of rat synaptosomes) and psychosocial variables (baseline psychopathology and psychosocial impairment). The candidate' s training and research experiences during the RCDA will enable him to pursue larger, more scientifically rigorous pharmacologic trials of youth with ADHD and depressive or other comorbid psychopathology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BUPROPION SR IN ATYPICAL DEPRESSION Principal Investigator & Institution: Golden, Robert; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, NC 27599 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BUPROPION SR ON SLEEP Principal Investigator & Institution: Poland, Russell E.; Harbor-Ucla Research & Educ Inst 1124 W Carson St Torrance, CA 90502 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BUPROPION TO PREVENT POSTPARTUM SMOKING RELAPSE Principal Investigator & Institution: Dalton, Madeline A.; Assistant Professor; Pediatrics; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, NH 03755 Timing: Fiscal Year 2002; Project Start 01-MAY-2002; Project End 30-APR-2005 Summary: (provided by applicant) In this R21 grant application we propose to conduct pilot work that will lay the foundation for a randomized clinical trial of bupropion SR to prevent smoking relapse in postpartum women. Although many women quit smoking during pregnancy, up to 70 percent are smoking again within one year of delivery. Behavioral interventions designed to prevent relapse following delivery have met with only limited success. At the same time, several trials have demonstrated that bupropion SR is safe and effective in promoting cessation. However, there are no
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published studies evaluating the effectiveness of bupropion SR in preventing relapse during particularly vulnerable periods, such as the postpartum period. Our ultimate goal is to evaluate the effectiveness of bupropion SR in preventing relapse during the postpartum period among women who quit smoking during pregnancy and are abstinent at the time of delivery through a double-blind, placebo-controlled, randomized clinical trial. This pilot study will allow us to develop and fine tune the methodology for the trial and demonstrate our ability to enroll and follow participants. In this study, we will enroll 50 women at the time of delivery and randomly assign them to receive placebo or bupropion SR for 12 weeks. Our objectives are to: a) test protocols for recruitment, sample collection, and follow-up; b) develop survey instruments; c) evaluate patient compliance; and d) estimate eligibility, participation, and retention rates for the larger trial. Patients and investigators will be blind to treatment assignment. Subjects in the treatment group will receive 300mg bupropion SR (150mg QD am for 7 days followed by 150mg BID for 11 weeks). Subjects in the control group will receive placebo following the same schedule. Both groups will receive 5 telephone-counseling sessions to encourage the maintenance of cessation in accordance with clinical practice guidelines. Patient compliance will be measured using the MEMS Track CapTM (Aprex Corporation, Union City, CA), which records each time and date the medication bottle is opened. Self-reported smoking status will be validated with a urine cotinine dipstick (
