Paxil - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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 , ...

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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., 1960Paxil: 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: 0-597-83632-9 1. Paxil-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.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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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 Paxil. 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 PAXIL......................................................................................................... 3 Overview........................................................................................................................................ 3 Federally Funded Research on Paxil .............................................................................................. 3 E-Journals: PubMed Central ......................................................................................................... 6 The National Library of Medicine: PubMed .................................................................................. 6 CHAPTER 2. NUTRITION AND PAXIL ............................................................................................... 23 Overview...................................................................................................................................... 23 Finding Nutrition Studies on Paxil............................................................................................. 23 Federal Resources on Nutrition ................................................................................................... 27 Additional Web Resources ........................................................................................................... 27 CHAPTER 3. ALTERNATIVE MEDICINE AND PAXIL ........................................................................ 29 Overview...................................................................................................................................... 29 National Center for Complementary and Alternative Medicine.................................................. 29 Additional Web Resources ........................................................................................................... 35 General References ....................................................................................................................... 36 CHAPTER 4. CLINICAL TRIALS AND PAXIL ..................................................................................... 37 Overview...................................................................................................................................... 37 Recent Trials on Paxil.................................................................................................................. 37 Keeping Current on Clinical Trials ............................................................................................. 40 CHAPTER 5. PATENTS ON PAXIL ..................................................................................................... 43 Overview...................................................................................................................................... 43 Patents on Paxil ........................................................................................................................... 43 Patent Applications on Paxil ....................................................................................................... 53 Keeping Current .......................................................................................................................... 64 CHAPTER 6. BOOKS ON PAXIL ......................................................................................................... 65 Overview...................................................................................................................................... 65 Book Summaries: Online Booksellers........................................................................................... 65 The National Library of Medicine Book Index ............................................................................. 66 Chapters on Paxil......................................................................................................................... 66 CHAPTER 7. PERIODICALS AND NEWS ON PAXIL ........................................................................... 69 Overview...................................................................................................................................... 69 News Services and Press Releases................................................................................................ 69 Newsletter Articles ...................................................................................................................... 73 Academic Periodicals covering Paxil ........................................................................................... 74 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 77 Overview...................................................................................................................................... 77 NIH Guidelines............................................................................................................................ 77 NIH Databases............................................................................................................................. 79 Other Commercial Databases....................................................................................................... 81 APPENDIX B. PATIENT RESOURCES ................................................................................................. 83 Overview...................................................................................................................................... 83 Patient Guideline Sources............................................................................................................ 83 Finding Associations.................................................................................................................... 85 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 87 Overview...................................................................................................................................... 87 Preparation................................................................................................................................... 87 Finding a Local Medical Library.................................................................................................. 87 Medical Libraries in the U.S. and Canada ................................................................................... 87 ONLINE GLOSSARIES.................................................................................................................. 93

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Contents Online Dictionary Directories ..................................................................................................... 93

PAXIL DICTIONARY ..................................................................................................................... 95 INDEX .............................................................................................................................................. 131

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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 Paxil is indexed in search engines, such as www.google.com or others, a nonsystematic 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 Paxil, 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 Paxil, 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 Paxil. 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 Paxil, 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 Paxil. 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 PAXIL Overview In this chapter, we will show you how to locate peer-reviewed references and studies on Paxil.

Federally Funded Research on Paxil The U.S. Government supports a variety of research studies relating to Paxil. 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 Paxil. 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 Paxil. The following is typical of the type of information found when searching the CRISP database for Paxil: •

Project Title: GENETIC ANALYSIS OF NEMATODE EGG LAYING Principal Investigator & Institution: Horvitz, H R.; Professor; Biology; Massachusetts Institute of Technology Cambridge, MA 02139 Timing: Fiscal Year 2001; Project Start 01-JAN-1978; Project End 31-DEC-2004 Summary: The long-term objective of this proposal is to understand how genes specify the structure, functioning and development of a behavioral system. Toward this end, the anatomically simple egg-laying system of the nematode Caenorhabditis elegans will be

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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analyzed. Mutants abnormal in egg laying will be used to define both cells that act in egg laying and genes that control the development and functioning of those cells. Four distinct components of the egg-laying system will be analyzed: the vulva (through which eggs are laid); the egg-laying musculature; the nerve cells that directly control the egg-laying musculature; and nerve cells that indirectly regulate egg laying. Vulval development provides an excellent model for both intercellular signaling (how cells communicate) and morphogenesis (how cells generate complex three-dimensional structures). The studies of intercellular signaling in vulval development should reveal the normal biological functions and interactions of genes with human counterparts responsible for cancer. The studies of vulval morphogenesis focus on genes that are involved in the synthesis of specific carbohydrates and that appear to be similar to human genes involved in connective tissue disorders and aging. The contraction of muscles in general and of the C. elegans egg-laying muscles in particular requires the movement of ions through channels that span muscle membranes. The studies of the egg-laying musculature focus on a new class of ion channels and promise to establish new biological roles for ion channels and suggest candidate genes for diseases in which such channels are abnormal. Studies of the two classes of nerve cells (HSNs and VCs) that innervate the egg-laying muscles should help establish molecular genetic mechanisms responsible for many features of nerve cell development and activity, including the determination of cell identity, the outgrowth and branching of processes, and the formation and functioning of synapses (which allow communication between a nerve cell and its targets). Many genes involved in the development of these nerve cells have human counterparts associated with disease. Finally, nerve cells that control both egg laying and other behaviors, e.g., locomotion, will be identified and analyzed based on their effects on how the animal modulates its behavior in response to its environment and experience. Some of these cells communicate using the neurotransmitter serotonin, the target of major pharmaceutical agents used to treat depression -- Prozac, Paxil and Zoloft. In addition, how the environment and experience modulate behavior is a fundamental problem in neuroscience, and these studies should establish cellular and molecular mechanisms responsible for how sensory stimuli regulate behavior and how information about past experience is stored and retrieved. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: METHOD FOR MAKING AN IMPROVED ST JOHN'S WORT PRODUCT Principal Investigator & Institution: Castor, Trevor P.; President & Chief Executive Officer; Aphios Corporation 3-E Gill St Woburn, MA 01801 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-DEC-2002 Summary: (Adapted from the application): The goal of this Phase I/Phase II Fast Track project is to develop an improved St. John's Wort product which can be manufactured in a standardized and reproducible manner. St. John's Wort contains multiple bioactive compounds that have been used in a wide variety of ailments, most notably endogenous depression. The approach involves the use of supercritical fluids and near-critical fluids with and without polar cosolvents such as alcohols (trademarked as SuperFluids). These fluids are gases such as carbon dioxide which when compressed exhibit enhanced thermodynamic properties that can be fine-tuned for rapid and selective extraction of bioactive molecules. In Phase I, optimal conditions for selective SuperFluids extraction of and chromatographic purification of St. John's Wort will be established. In preliminary studies, this was accomplished by following the extraction of bioactive compounds with super critical carbon dioxide with 0 to 20% methanol. The results of

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Phase I studies will be used to develop a large scale manufacturing process. In a Phase II investigation, the conditions for selective extraction and chromatographic purification of bioactive compounds will be further optimized in terms of mechanical components, enhancement devices and operating parameters. Finally, it is proposed to design, build and test a pilot-scale prototype plant that could operate under cGMP conditions. Paracelsian (Ithaca, NY) will perform serotonin uptake assays on contract. PROPOSED COMMERCIAL APPLICATION: Among the most widely prescribed antidepressants in the United States are Prozac from Eli Lilly, Zoloft from Pfizer and Paxil from SmithKline Beecham. The worldwide sales of the top selling antidepressants are approximately $4.8 billion. As people experience adverse side-effects from prescription antidepressants, there has been a concomitant rise in the use of St. John's Wort and other herbs as natural antidepressants. This Phase I/Phase II Fast Track SBIR project should lead to the development of a biologically-enhanced, stable and standardized St. John's Wort product that can be manufactured under cGMP conditions to provide a natural alternative with reduced side effects of Prozac, Pfizer and Paxil, and thus satisfy a burgeoning market demand in the $4.8 billion antidepressant marketplace. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: SSRI TREATMENT OF PRENATAL COCAINE-INDUCED 5HT DEFICITS Principal Investigator & Institution: Battaglia, George; Associate Professor; Pharmacol & Exper Therapeutics; Loyola University Medical Center Lewis Towers, 13Th Fl Chicago, IL 60611 Timing: Fiscal Year 2001; Project Start 01-APR-1993; Project End 31-DEC-2004 Summary: (applicant's abstract): Various mood disorders are being increasingly diagnosed in offspring exposed to cocaine in utero. In humans, impairments in serotonin (5-HT) function are associated with disorders such as anxiety, depression and increased impulsivity and aggression. During the initial funding period, we identified long-term neurochemical and functional impairments in brain 5-HT systems in rat offspring exposed prenatally to cocaine. Thus, the long-term objective of this research is to determine the effectiveness of clinically prescribed serotonin-selective reuptake inhibitors (SSRIs) to treat mood disorders in offspring resulting from prenatal exposure to cocaine. The clinical efficacy of SSRIs is related to their ability to produce neuroadaptive changes in 5-HT systems. This renewal application will determine if clinically used SSRIs, such as paroxetine (Paxil), will be effective in reversing the serotonergic deficits in rats produced by prenatal cocaine exposure. Our HYPOTHESIS is that SSRIs will be effective in restoring brain 5-HT function and producing neuroadaptive changes in 5-HT receptor signal transduction in prenatal cocaineexposed offspring. This proposal will determine the mechanisms responsible for 5-HT impairments and the restoration of 5-HT function by SSRIs in offspring using biochemical, neurochemical and neuroendocrine measures to study pre- and postsynaptic components of 5-HT pathways. Each aim will study the mechanism of neuroadaptive changes in different components of the 5-HT signal transduction pathway due to prenatal cocaine and subsequent postnatal SSRI treatment. Aim 1 will focus on presynaptic 5-HT terminal function; aim 2 will investigate the sensitivity of somatodendritic 5-HT1A autoreceptors on 5-HT cell bodies; and aims 3 & 4 will investigate postsynaptic function of 5-HT1A and 5-HT2A receptor signal transduction systems, respectively. Because neuroendocrine challenge can also be used in humans, the correspondence between neurochemical changes in brain induced changes in 5-HTmediated neuroendocrine responses will provide the foundation to assess prenatal

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cocaine-induced changes in 5-HT function in human offspring. In addition, our studies will identify the mechanisms mediating SSRI-induced neuroadaptive changes in 5-HT systems in offspring impaired by prenatal cocaine. Data obtained from the proposed studies will be important in predicting the potential efficacy of SSRIs in treating disorders in individuals previously exposed to cocaine in utero. To our knowledge, these studies are the first to determine the utility of SSRIs to treat impairments in 5-HT function due to prenatal cocaine exposure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “Paxil” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for Paxil in the PubMed Central database: •

Paroxetine (Paxil, Seroxat): increased risk of suicide in pediatric patients. by Wooltorton E. 2003 Sep 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=183305

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Postural hypotension induced by paroxetine. by Andrews C, Pinner G. 1998 Feb 21; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28465

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Rapid resolution of social anxiety disorder, selective mutism, and separation anxiety with paroxetine in an 8-year-old girl. by Lehman RB. 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=exter nal&artid=161642

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to

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Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print. 6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with Paxil, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “Paxil” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for “Paxil” (hyperlinks lead to article summaries): •

A case of paroxetine-induced galactorrhea. Author(s): Davenport E, Velamoor R. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2002 November; 47(9): 890-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500767&dopt=Abstract

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A comparison of paroxetine and amisulpride in the treatment of dysthymic disorder. Author(s): Rocca P, Fonzo V, Ravizza L, Rocca G, Scotta M, Zanalda E, Bogetto F. Source: Journal of Affective Disorders. 2002 August; 70(3): 313-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12128243&dopt=Abstract

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A comparison of paroxetine versus paroxetine plus amisulpride in the treatment of dysthymic disorder: efficacy and psychosocial outcomes. Author(s): Rocca P, Marchiaro L, Rasetti R, Rivoira E, Bogetto F. Source: Psychiatry Research. 2002 October 10; 112(2): 145-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12429360&dopt=Abstract

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A double-blind placebo-controlled study of the efficacy and safety of paroxetine in the treatment of pathological gambling. Author(s): Kim SW, Grant JE, Adson DE, Shin YC, Zaninelli R. Source: The Journal of Clinical Psychiatry. 2002 June; 63(6): 501-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088161&dopt=Abstract

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A pilot trial assessing the efficacy of paroxetine hydrochloride (Paxil) in controlling hot flashes in breast cancer survivors. Author(s): Stearns V, Isaacs C, Rowland J, Crawford J, Ellis MJ, Kramer R, Lawrence W, Hanfelt JJ, Hayes DF. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 2000 January; 11(1): 17-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10690382&dopt=Abstract

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A pilot trial of paroxetine for the treatment of hot flashes and associated symptoms in women with breast cancer. Author(s): Weitzner MA, Moncello J, Jacobsen PB, Minton S. Source: Journal of Pain and Symptom Management. 2002 April; 23(4): 337-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11997203&dopt=Abstract

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A prospective study comparing paroxetine alone versus paroxetine plus sildenafil in patients with premature ejaculation. Author(s): Salonia A, Maga T, Colombo R, Scattoni V, Briganti A, Cestari A, Guazzoni G, Rigatti P, Montorsi F. Source: The Journal of Urology. 2002 December; 168(6): 2486-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12441946&dopt=Abstract

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A randomized trial comparing paroxetine and venlafaxine in the treatment of bipolar depressed patients taking mood stabilizers. Author(s): Vieta E, Martinez-Aran A, Goikolea JM, Torrent C, Colom F, Benabarre A, Reinares M. Source: The Journal of Clinical Psychiatry. 2002 June; 63(6): 508-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088162&dopt=Abstract

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A randomized, double-blind, 24-week study comparing the efficacy and tolerability of mirtazapine and paroxetine in depressed patients in primary care. Author(s): Wade A, Crawford GM, Angus M, Wilson R, Hamilton L. Source: International Clinical Psychopharmacology. 2003 May; 18(3): 133-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12702891&dopt=Abstract

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A randomized, double-blind, placebo-controlled study of the effects of adjunctive paroxetine in panic disorder patients unsuccessfully treated with cognitivebehavioral therapy alone. Author(s): Kampman M, Keijsers GP, Hoogduin CA, Hendriks GJ. Source: The Journal of Clinical Psychiatry. 2002 September; 63(9): 772-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12363116&dopt=Abstract

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A randomized, placebo-controlled trial of paroxetine in nursing home residents with non-major depression. Author(s): Burrows AB, Salzman C, Satlin A, Noble K, Pollock BG, Gersh T. Source: Depression and Anxiety. 2002; 15(3): 102-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12001178&dopt=Abstract

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Acute changes in cerebrospinal fluid 5-HIAA following oral paroxetine challenge in healthy humans. Author(s): Carpenter LL, Anderson GM, Siniscalchi JM, Chappell PB, Price LH. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 February; 28(2): 339-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12589387&dopt=Abstract

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Acute dystonic reaction in an elderly patient with mood disorder after titration of paroxetine: possible mechanisms and implications for clinical care. Author(s): Arnone D, Hansen L, Kerr JS. Source: Journal of Psychopharmacology (Oxford, England). 2002 December; 16(4): 395-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12503843&dopt=Abstract

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An exploratory study: the use of paroxetine for methamphetamine craving. Author(s): Piasecki MP, Steinagel GM, Thienhaus OJ, Kohlenberg BS. Source: J Psychoactive Drugs. 2002 July-September; 34(3): 301-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12422941&dopt=Abstract

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Antidepressive treatment with amitriptyline and paroxetine: effects on saliva cortisol concentrations. Author(s): Deuschle M, Hamann B, Meichel C, Krumm B, Lederbogen F, Kniest A, Colla M, Heuser I. Source: Journal of Clinical Psychopharmacology. 2003 April; 23(2): 201-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12640223&dopt=Abstract

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Apparent mechanism-based inhibition of human CYP2D6 in vitro by paroxetine: comparison with fluoxetine and quinidine. Author(s): Bertelsen KM, Venkatakrishnan K, Von Moltke LL, Obach RS, Greenblatt DJ. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2003 March; 31(3): 289-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12584155&dopt=Abstract

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Are paroxetine, fluoxetine, and sertraline equally effective for depression? Author(s): Straton JB, Cronholm P. Source: The Journal of Family Practice. 2002 March; 51(3): 285. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11978244&dopt=Abstract

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By the way, doctor. I've been taking Paxil for depression for about six months. Although it's helped my symptoms of depression, I've lost interest in sex. Aside from stopping the medication, is there any way to regain my sexual function? Author(s): Robb-Nicholson C. Source: Harvard Women's Health Watch. 2001 February; 8(6): 7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11175469&dopt=Abstract

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Citalopram treatment of paroxetine-intolerant depressed patients. Author(s): Thase ME, Ferguson JM, Lydiard RB, Wilcox CS. Source: Depression and Anxiety. 2002; 16(3): 128-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415538&dopt=Abstract

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Clinical and neurobiological effects of tianeptine and paroxetine in major depression. Author(s): Nickel T, Sonntag A, Schill J, Zobel AW, Ackl N, Brunnauer A, Murck H, Ising M, Yassouridis A, Steiger A, Zihl J, Holsboer F. Source: Journal of Clinical Psychopharmacology. 2003 April; 23(2): 155-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12640217&dopt=Abstract

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Cytochrome P450 2D6 genotype does not predict SSRI (fluoxetine or paroxetine) induced hyponatraemia. Author(s): Stedman CA, Begg EJ, Kennedy MA, Roberts R, Wilkinson TJ. Source: Human Psychopharmacology. 2002 June; 17(4): 187-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12404686&dopt=Abstract

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Decreased lymphocyte 3H-paroxetine binding in obsessive-compulsive disorder. Author(s): Marazziti D, Baroni S, Masala I, Giannaccini G, Mungai F, Di Nasso E, Cassano GB. Source: Neuropsychobiology. 2003; 47(3): 128-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12759554&dopt=Abstract

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Depression after cardiac transplant treated with interpersonal psychotherapy and paroxetine. Author(s): Miller M. Source: American Journal of Psychotherapy. 2002; 56(4): 555-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12520890&dopt=Abstract

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Differential brain metabolic predictors of response to paroxetine in obsessivecompulsive disorder versus major depression. Author(s): Saxena S, Brody AL, Ho ML, Zohrabi N, Maidment KM, Baxter LR Jr. Source: The American Journal of Psychiatry. 2003 March; 160(3): 522-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12611834&dopt=Abstract

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Differential effects of amitriptyline, nefazodone and paroxetine on performance and brain indices of visual selective attention and working memory. Author(s): van Laar MW, Volkerts ER, Verbaten MN, Trooster S, van Megen HJ, Kenemans JL. Source: Psychopharmacology. 2002 August; 162(4): 351-63. Epub 2002 June 05. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172688&dopt=Abstract

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Discontinuation symptoms: comparison of brief interruption in fluoxetine and paroxetine treatment. Author(s): Judge R, Parry MG, Quail D, Jacobson JG. Source: International Clinical Psychopharmacology. 2002 September; 17(5): 217-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12177584&dopt=Abstract

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Discontinuing paroxetine: a personal account. Author(s): Shoenberger D. Source: Psychotherapy and Psychosomatics. 2002 July-August; 71(4): 237-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12097790&dopt=Abstract

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Does 5-HT restrain panic? A tryptophan depletion study in panic disorder patients recovered on paroxetine. Author(s): Bell C, Forshall S, Adrover M, Nash J, Hood S, Argyropoulos S, Rich A, Nutt DJ. Source: Journal of Psychopharmacology (Oxford, England). 2002 March; 16(1): 5-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11949771&dopt=Abstract

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Does a preexisting anxiety disorder predict response to paroxetine in irritable bowel syndrome? Author(s): Masand PS, Gupta S, Schwartz TL, Kaplan D, Virk S, Hameed A, Lockwood K. Source: Psychosomatics. 2002 November-December; 43(6): 451-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12444227&dopt=Abstract

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Double-blind, randomized comparison of mirtazapine and paroxetine in elderly depressed patients. Author(s): Schatzberg AF, Kremer C, Rodrigues HE, Murphy GM Jr; Mirtazapine vs. Paroxetine Study Group. Source: The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry. 2002 September-October; 10(5): 541-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12213688&dopt=Abstract

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Early improvement under mirtazapine and paroxetine predicts later stable response and remission with high sensitivity in patients with major depression. Author(s): Szegedi A, Muller MJ, Anghelescu I, Klawe C, Kohnen R, Benkert O. Source: The Journal of Clinical Psychiatry. 2003 April; 64(4): 413-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12716243&dopt=Abstract

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EEG correlates of acute and chronic paroxetine treatment in depression. Author(s): Knott V, Mahoney C, Kennedy S, Evans K. Source: Journal of Affective Disorders. 2002 May; 69(1-3): 241-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12103473&dopt=Abstract

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Effect of nortriptyline and paroxetine on CYP2D6 activity in depressed elderly patients. Author(s): Solai LK, Pollock BG, Mulsant BH, Frye RF, Miller MD, Sweet RA, Kirshner M, Sorisio D, Begley A, Reynolds CF 3rd. Source: Journal of Clinical Psychopharmacology. 2002 October; 22(5): 481-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352271&dopt=Abstract

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Effect of potent CYP2D6 inhibition by paroxetine on atomoxetine pharmacokinetics. Author(s): Belle DJ, Ernest CS, Sauer JM, Smith BP, Thomasson HR, Witcher JW. Source: Journal of Clinical Pharmacology. 2002 November; 42(11): 1219-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12412820&dopt=Abstract

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Effects on sleep architecture of pindolol, paroxetine and their combination in healthy volunteers. Author(s): Bell C, Wilson S, Rich A, Bailey J, Nutt D. Source: Psychopharmacology. 2003 March; 166(2): 102-10. Epub 2003 January 21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12536263&dopt=Abstract

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Efficacy and tolerability of controlled-release and immediate-release paroxetine in the treatment of depression. Author(s): Golden RN, Nemeroff CB, McSorley P, Pitts CD, Dube EM. Source: The Journal of Clinical Psychiatry. 2002 July; 63(7): 577-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12143913&dopt=Abstract

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Efficacy and tolerability of Paroxetine 20 mg daily in the treatment of depression and depression associated anxiety. Author(s): Chaudhry HR, Qureshi Z, Tareen IA, Yazdani I. Source: J Pak Med Assoc. 2002 November; 52(11): 518-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12585372&dopt=Abstract

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Efficacy and tolerability of paroxetine for the long-term treatment of generalized anxiety disorder. Author(s): Stocchi F, Nordera G, Jokinen RH, Lepola UM, Hewett K, Bryson H, Iyengar MK; Paroxetine Generalized Anxiety Disorder Study Team. Source: The Journal of Clinical Psychiatry. 2003 March; 64(3): 250-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12716265&dopt=Abstract

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Efficacy of paroxetine for relapse prevention in social anxiety disorder: a 24-week study. Author(s): Stein DJ, Versiani M, Hair T, Kumar R. Source: Archives of General Psychiatry. 2002 December; 59(12): 1111-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12470127&dopt=Abstract

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Focus on paroxetine. Author(s): Green B. Source: Current Medical Research and Opinion. 2003; 19(1): 13-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12661775&dopt=Abstract

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Frontotemporal dementia: paroxetine as a possible treatment of behavior symptoms. A randomized, controlled, open 14-month study. Author(s): Moretti R, Torre P, Antonello RM, Cazzato G, Bava A. Source: European Neurology. 2003; 49(1): 13-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12464713&dopt=Abstract

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High-performance liquid chromatography-mass spectrometry method for the determination of paroxetine in human plasma. Author(s): Zhu Z, Neirinck L. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2002 November 25; 780(2): 295-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12401355&dopt=Abstract

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Improved sample preparation for the quantitative analysis of paroxetine in human plasma by stable isotope dilution negative ion chemical ionisation gas chromatography-mass spectrometry. Author(s): Leis HJ, Windischhofer W, Fauler G. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2002 November 5; 779(2): 353-57. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12361750&dopt=Abstract

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Increased concentration of corticosteroid-binding globulin due to antidepressant treatment with amitritpyline, but not paroxetine. Author(s): Deuschle M, Luppa P, Hamann B, Nonell A, Heuser I. Source: Journal of Psychiatric Research. 2003 January-February; 37(1): 85-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12482473&dopt=Abstract

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Influence of the selective serotonin re-uptake inhibitor, paroxetine, on gastric sensorimotor function in humans. Author(s): Tack J, Broekaert D, Coulie B, Fischler B, Janssens J. Source: Alimentary Pharmacology & Therapeutics. 2003 February 15; 17(4): 603-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12622770&dopt=Abstract

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Inhibition of norepinephrine uptake in patients with major depression treated with paroxetine. Author(s): Gilmor ML, Owens MJ, Nemeroff CB. Source: The American Journal of Psychiatry. 2002 October; 159(10): 1702-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359676&dopt=Abstract

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Lamotrigine as adjunct to paroxetine in acute depression: a placebo-controlled, double-blind study. Author(s): Normann C, Hummel B, Scharer LO, Horn M, Grunze H, Walden J. Source: The Journal of Clinical Psychiatry. 2002 April; 63(4): 337-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12000208&dopt=Abstract

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Lawyers may seek judicial review of panel reviewing paroxetine. Author(s): Dobson R. Source: Bmj (Clinical Research Ed.). 2003 March 22; 326(7390): 618. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649225&dopt=Abstract

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Major depression with ischemic heart disease: effects of paroxetine and nortriptyline on long-term heart rate variability measures. Author(s): Yeragani VK, Pesce V, Jayaraman A, Roose S. Source: Biological Psychiatry. 2002 September 1; 52(5): 418-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12242058&dopt=Abstract

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Major depression with ischemic heart disease: effects of paroxetine and nortriptyline on measures of nonlinearity and chaos of heart rate. Author(s): Yeragani VK, Roose S, Mallavarapu M, Radhakrishna RK, Pesce V. Source: Neuropsychobiology. 2002; 46(3): 125-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12422059&dopt=Abstract

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Minor strokes related to paroxetine discontinuation in an elderly subject: emergent adverse events. Author(s): Ramasubbu R. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2003 May; 48(4): 281-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776398&dopt=Abstract

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New dosage-reduction regime to avoid paroxetine discontinuation syndrome. Author(s): Pacheco Yanez L, Malo P, Etxebeste M, Aragues E, Medrano J. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2003 March; 48(2): 129-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12655918&dopt=Abstract

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Occupancy of brain serotonin transporters during treatment with paroxetine in patients with social phobia: a positron emission tomography study with 11C McN 5652. Author(s): Kent JM, Coplan JD, Lombardo I, Hwang DR, Huang Y, Mawlawi O, Van Heertum RL, Slifstein M, Abi-Dargham A, Gorman JM, Laruelle M. Source: Psychopharmacology. 2002 December; 164(4): 341-8. Epub 2002 September 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12457263&dopt=Abstract

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Olanzapine augmentation of paroxetine-refractory obsessive-compulsive disorder. Author(s): D'Amico G, Cedro C, Muscatello MR, Pandolfo G, Di Rosa AE, Zoccali R, La Torre D, D'Arrigo C, Spina E. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2003 June; 27(4): 619-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12787848&dopt=Abstract

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Palinopsia and paroxetine withdrawal. Author(s): Terao T. Source: The Journal of Clinical Psychiatry. 2002 April; 63(4): 368. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12000213&dopt=Abstract

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Paroxetine (Paxil) overdose: a pediatric focus. Author(s): Myers LB, Krenzelok EP. Source: Vet Hum Toxicol. 1997 April; 39(2): 86-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9080633&dopt=Abstract

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Paroxetine and fluoxetine effects on mood and cognitive functions in depressed nondemented elderly patients. Author(s): Cassano GB, Puca F, Scapicchio PL, Trabucchi M; Italian Study Group on Depression in Elderly Patients. Source: The Journal of Clinical Psychiatry. 2002 May; 63(5): 396-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12019663&dopt=Abstract

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Paroxetine as a 5-HT neuroendocrine probe. Author(s): Kojima H, Terao T, Iwakawa M, Soya A, Inoue N, Shiraishi Y, Son Y, Soeda S, Ueda N, Yoshimura R, Nakamura J. Source: Psychopharmacology. 2003 April; 167(1): 97-102. Epub 2003 February 25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12601506&dopt=Abstract

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Paroxetine associated hepatotoxicity: a report of 3 cases and a review of the literature. Author(s): Azaz-Livshits T, Hershko A, Ben-Chetrit E. Source: Pharmacopsychiatry. 2002 May; 35(3): 112-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12107856&dopt=Abstract

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Paroxetine controlled release in the treatment of menopausal hot flashes: a randomized controlled trial. Author(s): Stearns V, Beebe KL, Iyengar M, Dube E. Source: Jama : the Journal of the American Medical Association. 2003 June 4; 289(21): 2827-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12783913&dopt=Abstract

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Paroxetine for multiple chemical sensitivity syndrome. Author(s): Black DW. Source: The American Journal of Psychiatry. 2002 August; 159(8): 1436-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12153845&dopt=Abstract

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Paroxetine for the treatment of interferon-alpha-induced depression in chronic hepatitis C. Author(s): Kraus MR, Schafer A, Faller H, Csef H, Scheurlen M. Source: Alimentary Pharmacology & Therapeutics. 2002 June; 16(6): 1091-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12030950&dopt=Abstract

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Paroxetine for treatment of somatization disorder. Author(s): Okugawa G, Yagi A, Kusaka H, Kinoshita T. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2002 Fall; 14(4): 464-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12426419&dopt=Abstract

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Paroxetine in adolescent major depression. Author(s): Parsons M. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2002 April; 41(4): 364; Author Reply 364. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11931589&dopt=Abstract

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Paroxetine in adolescent major depression. Author(s): Weintrob A. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2002 April; 41(4): 363-4; Author Reply 364. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11931587&dopt=Abstract

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Paroxetine in the treatment of adolescent major depression. Author(s): Silveira R, Jainer AK, Singh R. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2002 November; 41(11): 1270; Author Reply 1271. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410066&dopt=Abstract

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Paroxetine in the treatment of adolescent major depression. Author(s): Correll CU, Pleak RR. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2002 November; 41(11): 1269; Author Reply 1270. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410065&dopt=Abstract

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Paroxetine must not be given to patients under 18. Author(s): Waechter F. Source: Bmj (Clinical Research Ed.). 2003 June 14; 326(7402): 1282. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12805134&dopt=Abstract

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Paroxetine treatment of generalized anxiety disorder: a double-blind, placebocontrolled study. Author(s): Rickels K, Zaninelli R, McCafferty J, Bellew K, Iyengar M, Sheehan D. Source: The American Journal of Psychiatry. 2003 April; 160(4): 749-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12668365&dopt=Abstract

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Paroxetine versus clomipramine in adolescents with severe major depression: a double-blind, randomized, multicenter trial. Author(s): Braconnier A, Le Coent R, Cohen D; DEROXADO Study Group. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2003 January; 42(1): 22-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12500073&dopt=Abstract

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Paroxetine-associated psoriasis. Author(s): Osborne SF, Stafford L, Orr KG. Source: The American Journal of Psychiatry. 2002 December; 159(12): 2113. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12450972&dopt=Abstract

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Paroxetine-induced enuresis. Author(s): Toros F, Erdogan K. Source: European Psychiatry : the Journal of the Association of European Psychiatrists. 2003 February; 18(1): 43-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12648899&dopt=Abstract

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Paroxetine-induced limb anesthesia. Author(s): Duggal HS. Source: General Hospital Psychiatry. 2003 January-February; 25(1): 51-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12583929&dopt=Abstract

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Paroxetine-induced somnambulism. Author(s): Kawashima T, Yamada S. Source: The Journal of Clinical Psychiatry. 2003 April; 64(4): 483. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12716257&dopt=Abstract

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Paroxetine-induced vaginal anaesthesia. Author(s): Michael A, Andrews S. Source: Pharmacopsychiatry. 2002 July; 35(4): 150-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12163985&dopt=Abstract

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Patient beliefs predict response to paroxetine among primary care patients with dysthymia and minor depression. Author(s): Sullivan MD, Katon WJ, Russo JE, Frank E, Barrett JE, Oxman TE, Williams JW Jr. Source: The Journal of the American Board of Family Practice / American Board of Family Practice. 2003 January-February; 16(1): 22-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12583647&dopt=Abstract

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Paxil and self-scratching. Author(s): Weintrob A. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2001 January; 40(1): 5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11195562&dopt=Abstract

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Perinatal outcome following third trimester exposure to paroxetine. Author(s): Costei AM, Kozer E, Ho T, Ito S, Koren G. Source: Archives of Pediatrics & Adolescent Medicine. 2002 November; 156(11): 1129-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12413342&dopt=Abstract

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Perinatal outcome following third-trimester exposure to paroxetine: an alternative interpretation. Author(s): Pryse-Phillips W, Yuen DE, Pham B. Source: Archives of Pediatrics & Adolescent Medicine. 2003 June; 157(6): 601. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796244&dopt=Abstract

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Persistence of cognitive impairment in geriatric patients following antidepressant treatment: a randomized, double-blind clinical trial with nortriptyline and paroxetine. Author(s): Nebes RD, Pollock BG, Houck PR, Butters MA, Mulsant BH, Zmuda MD, Reynolds CF 3rd. Source: Journal of Psychiatric Research. 2003 March-April; 37(2): 99-108. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842163&dopt=Abstract

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Photosensitivity induced by paroxetine. Author(s): Vilaplana J, Botey E, Lecha M, Herrero C, Romaguera C. Source: Contact Dermatitis. 2002 August; 47(2): 118-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12455545&dopt=Abstract

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Possible confusion of Paxil and paclitaxel. Author(s): Hoy RH. Source: Am J Hosp Pharm. 1993 June; 50(6): 1137. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8100118&dopt=Abstract

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Provoked bradycardia after paroxetine administration. Author(s): Pae CU, Kim JJ, Lee CU, Lee SJ, Chul-Lee CL, Paik IH. Source: General Hospital Psychiatry. 2003 March-April; 25(2): 142-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12676432&dopt=Abstract

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Quantitative electroencephalography in OCD patients treated with paroxetine. Author(s): Hansen ES, Prichep LS, Bolwig TG, John ER. Source: Clin Electroencephalogr. 2003 April; 34(2): 70-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12784904&dopt=Abstract

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Randomised controlled study of sleep after nefazodone or paroxetine treatment in out-patients with depression. Author(s): Hicks JA, Argyropoulos SV, Rich AS, Nash JR, Bell CJ, Edwards C, Nutt DJ, Wilson SJ. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2002 June; 180: 528-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12042232&dopt=Abstract

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Rapid resolution of social anxiety disorder, selective mutism, and separation anxiety with paroxetine in an 8-year-old girl. Author(s): Lehman RB. Source: Journal of Psychiatry & Neuroscience : Jpn. 2002 March; 27(2): 124-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11944508&dopt=Abstract

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Re: Treatment of premature ejaculation with paroxetine hydrochloride as needed: 2 single-blind placebo controlled crossover studies. Author(s): Motofei IG. Source: The Journal of Urology. 2002 October; 168(4 Pt 1): 1508-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352444&dopt=Abstract

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Reboxetine versus paroxetine versus placebo: effects on cognitive functioning in depressed patients. Author(s): Ferguson JM, Wesnes KA, Schwartz GE. Source: International Clinical Psychopharmacology. 2003 January; 18(1): 9-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12490769&dopt=Abstract

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Relationship between CYP 2D6 metabolic status and sexual dysfunction in paroxetine treatment. Author(s): Zourkova A, Hadasova E. Source: Journal of Sex & Marital Therapy. 2002 October-December; 28(5): 451-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12378847&dopt=Abstract

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Selective serotonin reuptake inhibitor paroxetine modulates motor behavior through practice. A double-blind, placebo-controlled, multi-dose study in healthy subjects. Author(s): Loubinoux I, Pariente J, Rascol O, Celsis P, Chollet F. Source: Neuropsychologia. 2002; 40(11): 1815-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12062893&dopt=Abstract

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Serotonin reuptake inhibitor (Paxil) does not prevent the vasovagal reaction associated with carotid sinus massage and/or lower body negative pressure in healthy volunteers. Author(s): Takata TS, Wasmund SL, Smith ML, Li JM, Joglar JA, Banks K, Kowal RC, Page RL, Hamdan MH. Source: Circulation. 2002 September 17; 106(12): 1500-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12234955&dopt=Abstract

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Severe weight gain induced by combination treatment with risperidone and paroxetine. Author(s): Fukui H, Murai T. Source: Clinical Neuropharmacology. 2002 September-October; 25(5): 269-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12410060&dopt=Abstract

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Spotlight on paroxetine in psychiatric disorders in adults. Author(s): Wagstaff AJ, Cheer SM, Matheson AJ, Ormrod D, Goa KL. Source: Cns Drugs. 2002; 16(6): 425-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12027788&dopt=Abstract

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State markers of depression in sleep EEG: dependency on drug and gender in patients treated with tianeptine or paroxetine. Author(s): Murck H, Nickel T, Kunzel H, Antonijevic IA, Schill J, Zobel A, Steiger A, Sonntag A, Holsboer F. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2003 February; 28(2): 348-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12589388&dopt=Abstract

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Surprising results in the study of paroxetine for generalized anxiety disorder. Author(s): Ballas CA. Source: The Journal of Clinical Psychiatry. 2002 June; 63(6): 536; Author Reply 536-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12088169&dopt=Abstract

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The cost-effectiveness of psychotherapy and paroxetine for severe irritable bowel syndrome. Author(s): Creed F, Fernandes L, Guthrie E, Palmer S, Ratcliffe J, Read N, Rigby C, Thompson D, Tomenson B; North of England IBS Research Group. Source: Gastroenterology. 2003 February; 124(2): 303-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12557136&dopt=Abstract

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The effects of paroxetine and tianeptine on peripheral biochemical markers in major depression. Author(s): Muck-Seler D, Pivac N, Sagud M, Jakovljevic M, Mihaljevic-Peles A. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2002 December; 26(7-8): 1235-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12502009&dopt=Abstract

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Treatment of depression with comorbid anxiety disorders: differential efficacy of paroxetine versus moclobemide. Author(s): Pini S, Amador XF, Dell'Osso L, Baldini Rossi N, Cassano P, Savino M, Cassano GB. Source: International Clinical Psychopharmacology. 2003 January; 18(1): 15-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12490770&dopt=Abstract

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Use of paroxetine for the treatment of depression and anxiety disorders in the elderly: a review. Author(s): Bourin M. Source: Human Psychopharmacology. 2003 April; 18(3): 185-90. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12672169&dopt=Abstract

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Very long half-life of paroxetine following intoxication in an extensive cytochrome P4502D6 metabolizer. Author(s): Hilleret H, Voirol P, Bovier P, Giannakopoulos P, Zullino D, Baumann P, Giroud C, Rivier L, Eap CB. Source: Therapeutic Drug Monitoring. 2002 August; 24(4): 567-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12142644&dopt=Abstract

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CHAPTER 2. NUTRITION AND PAXIL Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and Paxil.

Finding Nutrition Studies on Paxil The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “Paxil” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following information is typical of that found when using the “Full IBIDS Database” to search for “Paxil” (or a synonym): •

A randomized trial comparing paroxetine and venlafaxine in the treatment of bipolar depressed patients taking mood stabilizers. Author(s): Bipolar Disorders Program, Barcelona Stanley Foundation Research Center, IDIBAPS, Hospital Clinic, University of Barcelona, Spain. [email protected] Source: Vieta, Eduard Martinez Aran, Anabel Goikolea, Jose Manuel Torrent, Carla Colom, Francesc Benabarre, Antoni Reinares, Maria J-Clin-Psychiatry. 2002 June; 63(6): 508-12 0160-6689

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Absorption of paroxetine under various dietary conditions and following antacid intake. Author(s): Beecham-Wulfing Clinical Pharmacology Research Institute, Neuss, Federal Republic of Germany. Source: Greb, W H Brett, M A Buscher, G Dierdorf, H D von Schrader, H W Wolf, D Mellows, G Zussman, B D Acta-Psychiatr-Scand-Suppl. 1989; 35099-101 0065-1591

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Acute effects of venlafaxine and paroxetine on serotonergic transmission in human volunteers. Author(s): Department of Neuroscience and Psychiatry, University of Newcastle, Royal Victoria Infirmary, Newcastle NE1 4LP, UK. Source: Porter, R J McAllister Williams, R H Young, A H Psychopharmacology-(Berl). 1999 September; 146(2): 194-8 0033-3158

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Brain 5-HT neurotransmission during paroxetine treatment. Author(s): Warneford Hospital, Oxford. Source: Sargent, P A Williamson, D J Cowen, P J Br-J-Psychiatry. 1998 January; 17249-52 0007-1250

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Changes in cortical 5-HT2 receptors following 5-HTP and paroxetine administration in rats. Source: Koshikawa, N Maruyama, Y Oka, K Nomura, H Mori, E Kobayashi, M Stephenson, J D J-Nihon-Univ-Sch-Dent. 1988 September; 30(3): 218-26 0029-0432

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Circannual variations in the binding of [3H]lysergic acid diethylamide to serotonin2A receptors and of [3H]paroxetine to serotonin uptake sites in platelets from healthy volunteers. Author(s): Division of Clinical Pharmacology, Norrland University Hospital, Umea, Sweden. Source: Spigset, O Allard, P Mjorndal, T Biol-Psychiatry. 1998 May 15; 43(10): 774-80 0006-3223

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Dose-dependent inhibition of CYP1A2, CYP2C19 and CYP2D6 by citalopram, fluoxetine, fluvoxamine and paroxetine. Author(s): Department of Clinical Pharmacology, Odense University, Denmark. Source: Jeppesen, U Gram, L F Vistisen, K Loft, S Poulsen, H E Brosen, K Eur-J-ClinPharmacol. 1996; 51(1): 73-8 0031-6970

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Effect of potent CYP2D6 inhibition by paroxetine on atomoxetine pharmacokinetics. Author(s): Department of Clinical Pharmacology, Eli Lilly and Company, Indianapolis, Indiana 46285, USA. Source: Belle, D J Ernest, C S Sauer, J M Smith, B P Thomasson, H R Witcher, J W J-ClinPharmacol. 2002 November; 42(11): 1219-27 0091-2700

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Effect of SB-243213, a selective 5-HT(2C) receptor antagonist, on the rat sleep profile: a comparison to paroxetine. Author(s): Neurology-CEDD, GlaxoSmithKline, New Frontiers Science Park North, Third Avenue, Essex CM19 5AW, Harlow, UK. [email protected] Source: Smith, M I Piper, D C Duxon, M S Upton, N Pharmacol-Biochem-Behavolume 2002 April; 71(4): 599-605 0091-3057

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Effects of repeated selective serotonin reuptake inhibitor paroxetine treatments on mouse forced swimming. Author(s): Department of Neuropsychiatry, Akita University School of Medicine, Japan. Source: Akagawa, Y Masuda, Y Maruyama, A Shimizu, T Hishikawa, Y Methods-FindExp-Clin-Pharmacol. 1999 November; 21(9): 599-601 0379-0355

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In vivo voltammetric study of cortical 5-HT after administration of 5-HTP or paroxetine to phenelzine-treated rats. Source: Aoki, S Koshikawa, N Kobayashi, M Stephenson, J D J-Nihon-Univ-Sch-Dent. 1987 September; 29(3): 185-8 0029-0432

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Influence of paroxetine, branched-chain amino acids and tyrosine on neuroendocrine system responses and fatigue in humans. Author(s): Institute of Sports Games, German Sport University, Koln. Source: Struder, H K Hollmann, W Platen, P Donike, M Gotzmann, A Weber, K HormMetab-Res. 1998 April; 30(4): 188-94 0018-5043

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Inhibition of hippocampal 5-HT synthesis by fluoxetine and paroxetine: evidence for the involvement of both 5-HT1A and 5-HT1B/D autoreceptors. Author(s): Merck Sharp and Dohme, Neuroscience Research Centre, Harlow Essex, UK. Source: Barton, C L Hutson, P H Synapse. 1999 January; 31(1): 13-9 0887-4476

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Lower 3H-paroxetine binding in cerebral cortex of suicide victims is partly due to fewer high affinity, non-transporter sites. Author(s): Department of Neuroscience, New York State Psychiatric Institute, NY, USA. Source: Mann, J J Henteleff, R A Lagattuta, T F Perper, J A Li, S Arango, V J-NeuralTransm. 1996; 103(11): 1337-50

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No influence of the antidepressant paroxetine on carbamazepine, valproate and phenytoin. Author(s): University Clinic of Neurology, Hvidovre Hospital, Denmark. Source: Andersen, B B Mikkelsen, M Vesterager, A Dam, M Kristensen, H B Pedersen, B Lund, J Mengel, H Epilepsy-Res. 1991 Nov-December; 10(2-3): 201-4 0920-1211

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Paroxetine and amitriptyline augmentation of lithium in the treatment of major depression: a double-blind study. Author(s): Department of Psychiatry, Berlin Lithium Clinic, Freie Universitat Berlin, Germany. Source: Bauer, M Zaninelli, R Muller Oerlinghausen, B Meister, W J-ClinPsychopharmacol. 1999 April; 19(2): 164-71 0271-0749

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Psychopharmacological profile of the selective serotonin reuptake inhibitor, paroxetine: implication of noradrenergic and serotonergic mechanisms. Author(s): GIS Medicament, JE 2027 Neurobiologie de l'anxiete, Faculte de Medecine, Nantes, France. Source: Redrobe, J P Bourin, M Colombel, M C Baker, G B J-Psychopharmacol. 1998; 12(4): 348-55 0269-8811

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Reduction in serotonin synthesis following acute and chronic treatments with paroxetine, a selective serotonin reuptake inhibitor, in rat brain: an autoradiographic study with alpha-[14C]methyl-L-tryptophan(2). Author(s): Cone Laboratory for Neurosurgical Research, Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, 3801 University St., H3A 2B4, Montreal, Quebec, Canada. Source: Yamane, F Okazawa, H Blier, P Diksic, M Biochem-Pharmacol. 2001 December 1; 62(11): 1481-9 0006-2952

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Reserpine or chronic paroxetine treatments do not modify the vesicular monoamine transporter 2 expression in serotonin-containing regions of the rat brain. Author(s): Unite de Neuropsychopharmacologie Experimentale, UPRES-A CNRS 6036, IFRMP No. 23, Site universitaire du Madrillet, Avenue de l'Universite, 76800, Saint Etienne du Rouvray, France. Source: Vilpoux, C Leroux Nicollet, I Naudon, L Raisman Vozari, R Costentin, J Neuropharmacology. 2000 April 3; 39(6): 1075-82 0028-3908

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Retroperitoneal haematoma in a patient treated with acenocoumarol, phenytoin and paroxetine. Author(s): Department of Clinical Pharmacology, Hospital La Paz, Paseo de la Castellana, Madrid, Spain. Source: Abad Santos, F Carcas, A J F Capitan, C Frias, J Clin-Lab-Haematol. 1995 June; 17(2): 195-7 0141-9854

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Serotonergic function in major depression and effect of sertraline and paroxetine treatment. Author(s): Department of Psychiatry, Institution of Clinical Neuroscience, Karolinska Institute, St Goran's Hospital, Stockholm, Sweden. [email protected] Source: Stain Malmgren, R Khoury, A E Aberg Wistedt, A Tham, A Int-ClinPsychopharmacol. 2001 March; 16(2): 93-101 0268-1315

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Serotonin syndrome after lithium add-on medication to paroxetine. Author(s): Department of Psychiatry, Faculty of Medicine, University of Bonn, Germany. Source: Sobanski, T Bagli, M Laux, G Rao, M L Pharmacopsychiatry. 1997 May; 30(3): 106-7 0176-3679

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Synthesis and ligand binding of tropane ring analogues of paroxetine. Author(s): Research Triangle Institute, North Carolina 27709, USA. Source: Keverline Frantz, K I Boja, J W Kuhar, M J Abraham, P Burgess, J P Lewin, A H Carroll, F I J-Med-Chem. 1998 January 15; 41(2): 247-57 0022-2623

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Tolerability of combined treatment with lithium and paroxetine in patients with bipolar disorder and depression. Author(s): Department of Psychiatry, University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic, Pennsylvania 15213, USA. [email protected] Source: Fagiolini, A Buysse, D J Frank, E Houck, P R Luther, J F Kupfer, D J J-ClinPsychopharmacol. 2001 October; 21(5): 474-8 0271-0749

Nutrition 27

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMDHealth: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,,00.html

The following is a specific Web list relating to Paxil; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation (some Web sites are subscription based):

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•

Minerals Fluoxetine Source: Healthnotes, Inc. www.healthnotes.com Paroxetine Source: Healthnotes, Inc. www.healthnotes.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND PAXIL Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to Paxil. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to Paxil and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “Paxil” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to Paxil: •

5-HT(2A) receptor binding is reduced in drug-naive and unchanged in SSRIresponder depressed patients compared to healthy controls: a PET study. Author(s): Messa C, Colombo C, Moresco RM, Gobbo C, Galli L, Lucignani G, Gilardi MC, Rizzo G, Smeraldi E, Zanardi R, Artigas F, Fazio F. Source: Psychopharmacology. 2003 April; 167(1): 72-8. Epub 2003 March 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12632246&dopt=Abstract

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Adjunctive osteopathic manipulative treatment in women with depression: a pilot study. Author(s): Plotkin BJ, Rodos JJ, Kappler R, Schrage M, Freydl K, Hasegawa S, Hennegan E, Hilchie-Schmidt C, Hines D, Iwata J, Mok C, Raffaelli D. Source: J Am Osteopath Assoc. 2001 September; 101(9): 517-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11575038&dopt=Abstract

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Anxiety induced by repetitive transcranial magnetic stimulation is suppressed by chronic treatment of paroxetine in rats. Author(s): Isogawa K, Fujiki M, Akiyoshi J, Tsutsumi T, Horinouchi Y, Kodama K, Nagayama H. Source: Pharmacopsychiatry. 2003 January; 36(1): 7-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12649768&dopt=Abstract

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Brain mechanisms of social anxiety disorder. Author(s): Nutt DJ, Bell CJ, Malizia AL. Source: The Journal of Clinical Psychiatry. 1998; 59 Suppl 17: 4-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9811424&dopt=Abstract

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Brain metabolic changes associated with symptom factor improvement in major depressive disorder. Author(s): Brody AL, Saxena S, Mandelkern MA, Fairbanks LA, Ho ML, Baxter LR. Source: Biological Psychiatry. 2001 August 1; 50(3): 171-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11513815&dopt=Abstract

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Brain metabolic changes in major depressive disorder from pre- to post-treatment with paroxetine. Author(s): Brody AL, Saxena S, Silverman DH, Alborzian S, Fairbanks LA, Phelps ME, Huang SC, Wu HM, Maidment K, Baxter LR Jr. Source: Psychiatry Research. 1999 October 11; 91(3): 127-39. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10641577&dopt=Abstract

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Cerebral glucose metabolic response to combined total sleep deprivation and antidepressant treatment in geriatric depression. Author(s): Smith GS, Reynolds CF 3rd, Pollock B, Derbyshire S, Nofzinger E, Dew MA, Houck PR, Milko D, Meltzer CC, Kupfer DJ. Source: The American Journal of Psychiatry. 1999 May; 156(5): 683-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10327899&dopt=Abstract

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Changes in regional brain glucose metabolism measured with positron emission tomography after paroxetine treatment of major depression. Author(s): Kennedy SH, Evans KR, Kruger S, Mayberg HS, Meyer JH, McCann S, Arifuzzman AI, Houle S, Vaccarino FJ. Source: The American Journal of Psychiatry. 2001 June; 158(6): 899-905. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11384897&dopt=Abstract

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Differential brain metabolic predictors of response to paroxetine in obsessivecompulsive disorder versus major depression. Author(s): Saxena S, Brody AL, Ho ML, Zohrabi N, Maidment KM, Baxter LR Jr.

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Source: The American Journal of Psychiatry. 2003 March; 160(3): 522-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12611834&dopt=Abstract •

Differential cerebral metabolic changes with paroxetine treatment of obsessivecompulsive disorder vs major depression. Author(s): Saxena S, Brody AL, Ho ML, Alborzian S, Maidment KM, Zohrabi N, Ho MK, Huang SC, Wu HM, Baxter LR Jr. Source: Archives of General Psychiatry. 2002 March; 59(3): 250-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11879163&dopt=Abstract

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Dopamine D2 receptor binding before and after treatment of major depression measured by [123I]IBZM SPECT. Author(s): Klimke A, Larisch R, Janz A, Vosberg H, Muller-Gartner HW, Gaebel W. Source: Psychiatry Research. 1999 April 26; 90(2): 91-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10482381&dopt=Abstract

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Effects of Hypericum perforatum (St. John's wort) on passive avoidance in the rat: evaluation of potential neurochemical mechanisms underlying its antidepressant activity. Author(s): Misane I, Ogren SO. Source: Pharmacopsychiatry. 2001 July; 34 Suppl 1: S89-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11518084&dopt=Abstract

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Generalized anxiety disorder in primary care: emerging issues in management and treatment. Author(s): Culpepper L. Source: The Journal of Clinical Psychiatry. 2002; 63 Suppl 8: 35-42. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12044106&dopt=Abstract

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Glucose metabolic response to total sleep deprivation, recovery sleep, and acute antidepressant treatment as functional neuroanatomic correlates of treatment outcome in geriatric depression. Author(s): Smith GS, Reynolds CF 3rd, Houck PR, Dew MA, Ma Y, Mulsant BH, Pollock BG. Source: The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry. 2002 September-October; 10(5): 561-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12213690&dopt=Abstract

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Hyperforin, a major antidepressant constituent of St. John's Wort, inhibits serotonin uptake by elevating free intracellular Na+1. Author(s): Singer A, Wonnemann M, Muller WE.

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Source: The Journal of Pharmacology and Experimental Therapeutics. 1999 September; 290(3): 1363-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10454515&dopt=Abstract •

Increased 5-hydroxytryptamine-2 receptor binding in the frontal cortex of depressed patients responding to paroxetine treatment: a positron emission tomography scan study. Author(s): Zanardi R, Artigas F, Moresco R, Colombo C, Messa C, Gobbo C, Smeraldi E, Fazio F. Source: Journal of Clinical Psychopharmacology. 2001 February; 21(1): 53-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11199948&dopt=Abstract

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Liposomes bearing platelet proteins: a model for surface functions studies. Author(s): Dalencon F, Rosilio V, Puisieux F, Baszkin A, Wautier JL. Source: Biochimica Et Biophysica Acta. 1996 August 16; 1302(3): 241-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8765146&dopt=Abstract

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Localized orbitofrontal and subcortical metabolic changes and predictors of response to paroxetine treatment in obsessive-compulsive disorder. Author(s): Saxena S, Brody AL, Maidment KM, Dunkin JJ, Colgan M, Alborzian S, Phelps ME, Baxter LR Jr. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 1999 December; 21(6): 683-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10633474&dopt=Abstract

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Neurological recovery after prolonged verapamil-induced cardiac arrest. Author(s): Evans JS, Oram MP. Source: Anaesthesia and Intensive Care. 1999 December; 27(6): 653-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10631424&dopt=Abstract

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Occupancy of brain serotonin transporters during treatment with paroxetine in patients with social phobia: a positron emission tomography study with 11C McN 5652. Author(s): Kent JM, Coplan JD, Lombardo I, Hwang DR, Huang Y, Mawlawi O, Van Heertum RL, Slifstein M, Abi-Dargham A, Gorman JM, Laruelle M. Source: Psychopharmacology. 2002 December; 164(4): 341-8. Epub 2002 September 11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12457263&dopt=Abstract

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Occupancy of serotonin transporters by paroxetine and citalopram during treatment of depression: a [(11)C]DASB PET imaging study. Author(s): Meyer JH, Wilson AA, Ginovart N, Goulding V, Hussey D, Hood K, Houle S.


Source: The American Journal of Psychiatry. 2001 November; 158(11): 1843-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11691690&dopt=Abstract •

Omega-3 fatty acids for depression in pregnancy. Author(s): Chiu CC, Huang SY, Shen WW, Su KP. Source: The American Journal of Psychiatry. 2003 February; 160(2): 385. Erratum In: Am J Psychiatry. 2003 April; 160(4): 810. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562593&dopt=Abstract

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Pindolol augmentation of antidepressant treatment: recent contributions from brain imaging studies. Author(s): Martinez D, Broft A, Laruelle M. Source: Biological Psychiatry. 2000 October 15; 48(8): 844-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11063979&dopt=Abstract

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Psychological stress increases serotonin release in the rat amygdala and prefrontal cortex assessed by in vivo microdialysis. Author(s): Kawahara H, Yoshida M, Yokoo H, Nishi M, Tanaka M. Source: Neuroscience Letters. 1993 November 12; 162(1-2): 81-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8121642&dopt=Abstract

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Regional brain metabolic changes in patients with major depression treated with either paroxetine or interpersonal therapy: preliminary findings. Author(s): Brody AL, Saxena S, Stoessel P, Gillies LA, Fairbanks LA, Alborzian S, Phelps ME, Huang SC, Wu HM, Ho ML, Ho MK, Au SC, Maidment K, Baxter LR Jr. Source: Archives of General Psychiatry. 2001 July; 58(7): 631-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11448368&dopt=Abstract

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Retinopathy associated with high-dose interferon alfa-2b therapy. Author(s): Hejny C, Sternberg P, Lawson DH, Greiner K, Aaberg TM Jr. Source: American Journal of Ophthalmology. 2001 June; 131(6): 782-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11384576&dopt=Abstract

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Serotonin reuptake inhibitor (Paxil) does not prevent the vasovagal reaction associated with carotid sinus massage and/or lower body negative pressure in healthy volunteers. Author(s): Takata TS, Wasmund SL, Smith ML, Li JM, Joglar JA, Banks K, Kowal RC, Page RL, Hamdan MH. Source: Circulation. 2002 September 17; 106(12): 1500-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12234955&dopt=Abstract

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Serotonin uptake inhibitors modulate intracellular Ca2+ mobilization in platelets. Author(s): Helmeste DM, Tang SW, Reist C, Vu R.

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Source: European Journal of Pharmacology. 1995 February 15; 288(3): 373-7. Erratum In: Eur J Pharmacol 1995 July 18; 290(2): 173-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7774682&dopt=Abstract •

SSRIs and St.John's Wort: possible toxicity? Author(s): Gordon JB. Source: American Family Physician. 1998 March 1; 57(5): 950,953. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9518947&dopt=Abstract

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The differential effects of chlorpromazine and haloperidol on latent inhibition in healthy volunteers. Author(s): McCartan D, Bell R, Green JF, Campbell C, Trimble K, Pickering A, King DJ. Source: Journal of Psychopharmacology (Oxford, England). 2001 June; 15(2): 96-104. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11448094&dopt=Abstract

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The effect of paroxetine on 5-HT(2A) receptors in depression: an [(18)F]setoperone PET imaging study. Author(s): Meyer JH, Kapur S, Eisfeld B, Brown GM, Houle S, DaSilva J, Wilson AA, Rafi-Tari S, Mayberg HS, Kennedy SH. Source: The American Journal of Psychiatry. 2001 January; 158(1): 78-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11136637&dopt=Abstract

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The long-term treatment of panic disorder. Author(s): Davidson JR. Source: The Journal of Clinical Psychiatry. 1998; 59 Suppl 8: 17-21; Discussion 22-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9707158&dopt=Abstract

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Treatment of disequilibrium and nausea in the SRI discontinuation syndrome. Author(s): Schechter JO. Source: The Journal of Clinical Psychiatry. 1998 August; 59(8): 431-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9721826&dopt=Abstract

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Treatment of generalized anxiety disorder. Author(s): Gorman JM. Source: The Journal of Clinical Psychiatry. 2002; 63 Suppl 8: 17-23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12044104&dopt=Abstract


Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

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HealthGate: http://www.tnp.com/

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WebMDHealth: http://my.webmd.com/drugs_and_herbs

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,,00.html

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

The following is a specific Web list relating to Paxil; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation (some Web sites are subscription based): •

General Overview Depression Source: Healthnotes, Inc. www.healthnotes.com Depression Source: Integrative Medicine Communications; www.drkoop.com Eating Disorders Source: Healthnotes, Inc. www.healthnotes.com Fibromyalgia Source: Healthnotes, Inc. www.healthnotes.com Hypochondriasis Source: Integrative Medicine Communications; www.drkoop.com Post Traumatic Stress Disorder Source: Integrative Medicine Communications; www.drkoop.com

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PTSD Source: Integrative Medicine Communications; www.drkoop.com •

Herbs and Supplements 5-HTP Source: Integrative Medicine Communications; www.drkoop.com 5-Hydroxytryptophan Source: Healthnotes, Inc. www.healthnotes.com 5-Hydroxytryptophan (5-HTP) Source: Integrative Medicine Communications; www.drkoop.com Antidepressants Source: Healthnotes, Inc. www.healthnotes.com Clozapine Source: Healthnotes, Inc. www.healthnotes.com Fluvoxamine Source: Healthnotes, Inc. www.healthnotes.com Ginkgo biloba Source: Healthnotes, Inc. www.healthnotes.com Melaleuca Alternative names: Tea Tree Oil; Melaleuca alternifolia Source: Alternative Medicine Foundation, Inc. www.amfoundation.org Sertraline Source: Healthnotes, Inc. www.healthnotes.com

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. CLINICAL TRIALS AND PAXIL Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning Paxil.

Recent Trials on Paxil The following is a list of recent trials dedicated to Paxil.8 Further information on a trial is available at the Web site indicated. •

Cerebral Structure and Function Before and After Pharmacological and Psychological Treatment for PTSD Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: Posttraumatic stress disorder (PTSD) is characterized by intrusive recollections, avoidant behavior, anxiety and exaggerated fear response. The pathophysiology of PTSD is largely unknown. Neurophysiological testing in PTSD reveals deficits in memory and attention. Neuroimaging studies report increased amygdala and decreased anterior cingulated activation and reduced hippocampal volume. Clinical observations, psychophysiological measures and animal studies suggest that facilitated fear conditioning, delayed extinction, inescapable shock, sensitization and protracted habituation may contribute to the onset and persistence of PTSD. We propose to use fMRI and the psychophysiology lab to examine the effect of treatment with paroxetine and cognitive behavioral therapy on regional cerebral blood flow (rCBF) in brain regions conceivably involved in evolution and maintenance of PTSD: Amygdala, anterior cingulate and hippocampus. We will use emotional tasks that have elicited differences in perfusion or metabolism between patients with PTSD and trauma exposed and healthy subjects. Tasks performed in the fMRI will include 'masked' and 'unmasked' emotional faces paradigms and differential delay conditioning. Contextual fear provocation and eyeblink trace conditioning will be done in the psychophysiology lab. This evaluation will be performed before and after a 10-week period of treatment with paroxetine and a 10-session course of cognitive behavioral

8

These are listed at www.ClinicalTrials.gov.

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treatment (CBT). Study population will comprise the following matched female groups: Patients with PTSD due to sexual or physical assault; previously assaulted healthy women who have not suffered from PTSD and non traumatized health women. Subjects from the 1st group will either be treated with paroxetine for 10 weeks, undergo a 10week 'prolonged exposure' (PE) CBT course, or will be put on the 'waiting list.' It is assumed that variability in outcome will be observed in both treatment modes, which will enable us to seek treatment response predictors. It is unknown whether cerebral abnormalities in PTSD are state or trait phenomena. In depression and OCD, functional imaging research shows improvement in malfunctioning brain regions after clinically effective psychopharmacological and psychotherapeutic interventions and after administration of placebo in depression. An increase in hippocampal volume was found in patients with PTSD after treatment with paroxetine and after correction of the endocrine abnormality in Cushing's disorder. These findings support our expectation that at least some brain abnormalities in PTSD are state related, and that change in these abnormalities is demonstrable by fMRI. MEDLINEplus consumer health information Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00069225 •

Clonazepam and Paroxetine for Rapid Treatment of Post-Traumatic Stress Disorder Condition(s): Post Traumatic Stress Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: Post-Traumatic Stress Disorder (PTSD) is an anxiety disorder that follows exposure to an extremely traumatic stressors. PTSD is associated with serious symptoms. While numerous approaches have been used to treat PTSD, these treatments have several limiting factors. This study will evaluate a combination of the drugs clonazepam and paroxetine for the treatment of PTSD symptoms. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00025740

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Evaluation of Clonazepam and Paroxetine for Panic Disorder with Depression Condition(s): Panic Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to examine the safety and effectiveness of the drug combination paroxetine and clonazepam in treating people with panic disorder (PD) and major depression. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00031317

Clinical Trials 39

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Platelet Function in Patients Treated with SSRI and non-SSRI Antidepressants Condition(s): Depression Study Status: This study is currently recruiting patients. Sponsor(s): Warren G Magnuson Clinical Center (CC) Purpose - Excerpt: This study will examine the effect of a class of antidepressant medications called selective serotonin reuptake inhibitors (SSRIs) on platelet function. Platelets are small blood cells that help stop bleeding after injury to a blood vessel by forming a clot, or plug, in the vessel. Some medications impair platelet function, leading to increased bruising and bleeding. SSRIs decrease an important platelet component called serotonin, which may cause bleeding in some patients. SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox) and citalopram (Celexa). Patients 18 years of age and older being treated for depression with a SSRI or the non-SSRI bupropion (Wellbutrin) may be eligible for this study. Subjects will be recruited from a private clinic in Washington, D.C. Participants will provide a history of their current medications and past history of bleeding. They will have about 4 tablespoons of blood drawn for tests to measure blood cell counts and platelet function. The study takes about 1 hour. The results of the SSRI-treated group and the bupropiontreated group will be analyzed and compared. This study may provide information that will help health care providers make treatment decisions to minimize possible adverse effects of medications in patients with depression. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00009568

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Treatment of Depression in Parkinson's Disease Trial Condition(s): Parkinson Disease; Depression Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: The goal of this study is to evaluate the effectiveness and safety of two antidepressants--nortriptyline and paroxetine, compared to placebo in patients with Parkinson's disease and depression. Phase(s): Phase II Study Type: Interventional Contact(s): Allison Dicke 1-877-795-4673 Web Site: http://clinicaltrials.gov/ct/show/NCT00062738

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Treatment of Panic Disorder: Long Term Strategies Condition(s): Panic Disorder; Agoraphobia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: Cognitive behavior therapy (CBT) with or without medication has been used in the treatment of panic disorder (PD). The purpose of this study is 1) to determine whether nine months of maintenance cognitive-behavior therapy (CBT)

40 Paxil

significantly improves the likelihood of sustained improvement; and 2) to determine the acute acceptability and efficacy of medication therapy or continued CBT alone among patients who fail to respond sufficiently to an initial course of CBT alone. It has been found that patients with PD respond as well to CBT or medication alone as they do to a combination of the two. Since the combined treatments are expensive and CBT is associated with less risk of medical toxicity compared to medications, CBT alone will be used first. All patients will first receive CBT alone. If the patient responds to this therapy, the patient will be assigned randomly (like tossing a coin) to 1 of 2 groups. One group will continue to receive CBT (maintenance therapy) for 9 months. The other group of responders will not receive any further therapy. If a patient does not respond to CBT alone, he/she will be assigned randomly to 1 of 2 different groups. One group will receive paroxetine; the other will continue to receive CBT for a longer period. The response to treatment will be evaluated to see which regimen works best to treat PD. The study will last approximately 3 years. An individual may be eligible for this study if he/she has panic disorder with no more than mild agoraphobia (fear of being in public places) and is at least 18 years old. Phase(s): Phase III Study Type: Interventional Contact(s): Katherine Shear, PhD 1-412-624-1340 [email protected]; Susan Ray, PhD [email protected] or [email protected] Web Site: http://clinicaltrials.gov/ct/show/NCT00000368 •

Treatment Effects on Platelet Calcium in Hypertensive and Depressed Patients Condition(s): Depression; Hypertension Study Status: This study is not yet open for patient recruitment. Sponsor(s): Department of Veterans Affairs Medical Research Service; SmithKline Beecham Purpose - Excerpt: This study aims to determine if treatment with an SSRI antidepressant medication, paroxetine, is associated with cellular calcium response to serotonin, platelet serotonin receptors, and improvement in mood in depressed patients with or without hypertension. It is hypothesized that platelets of hypertensive patients with depressive symptomatology with be hyper-responsive to serotonin. Additionally, treatment with an SSRI antidepressant is expected to produce a down-regulation of the serotonin receptor with an associated reduction in platelet cytosolic calcium response as well as improved mood. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018759

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions.

Clinical Trials 41

The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “Paxil” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

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CHAPTER 5. PATENTS ON PAXIL Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “Paxil” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Paxil, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Paxil By performing a patent search focusing on Paxil, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will

9Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on Paxil: •

Amorphous paroxetine composition Inventor(s): El-Rashidy; Ragab (Deerfield, IL), Sadhale; Yogesh D. (Palatine, IL), Ronsen; Bruce (River Forest, IL) Assignee(s): Pentech Pharmaceuticals, Inc. (Rolling Meadows, IL) Patent Number: 6,503,927 Date filed: October 28, 1999 Abstract: A stable amorphous paroxetine hydrochloride composition suitable as a therapeutic agent is prepared employing an aqueous solvent medium containing an acidulant and polyvinylpyrrolidone and drying the resulting solid dispersion. The preferred compositions include amorphous paroxetine hydrochloride, polyvinylpyrrolidone and citric acid. Excerpt(s): This invention relates to an amorphous paroxetine composition suitable as a therapeutic agent.... The selective serotonin reuptake inhibitor (SSRI) antidepressants have recently emerged as effective new treatments for patients with premature ejaculation. In general, antidepressants influence more than one neurotransmitter system and have affinity for multiple receptors. This heterogeneity of action produces mixed effects, including those on the sexual response cycle. Sexual dysfunction associated with antidepressants, including delayed and completely abolished ejaculation, has been a subject of numerous case reports, studies, and review articles [for example, J. Clin. Psychiatry 54, 209-212, (1993); J. Clin. Psychopharmacol. 3, 76-79, (1983); J. Clin. Psychiatry Mon. 10, 4-10, (1992); Depression 2, 233-240, (1994/1995)]. Because of the lack of abuse potential, relatively benign side effect profile, and fairly consistent reports of delayed ejaculation, SSRI antidepressants seem to be a safe treatment option for patients with premature ejaculation, especially in cases of failed psychological treatment.... The use of the SSRI antidepressant fluoxetine hydrochloride (Prozac.RTM.) in this regard has been described in U.S. Pat. No. 5,151,448 to Crenshaw et al. A similar treatment, at a relatively lower dosage of active ingredient, has been described in U.S. Pat. No. 5,276,042 to Crenshaw et al. for the SSRI antidepressant paroxetine hydrochloride (Paxil.RTM.). Other anti-anxiety drugs such as chlordiazepoxide (Librium.RTM.) and diazepam (Valium.RTM.) are not suitable for the treatment of premature ejaculation. Web site: http://www.delphion.com/details?pn=US06503927__

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Anti-depressant crystalline paroxetine hydrochloride hemihydrate Inventor(s): Buxton; Philip C. (Epsom, GB2), Richardson; John E. (Harlow, GB2), Lynch; Ian R. (Epsom, GB2), Curzons; Alan D. (Worthing, GB2), Wood-Kaczmar; Marian W. (Harlow, GB2), Barnes; Roger D. (Betchworth, GB2) Assignee(s): Beecham Group p.l.c. (Brentford, GB2) Patent Number: 4,721,723 Date filed: October 23, 1986

Patents 45

Abstract: The invention provides crystalline paroxetine hydrochloride hemihydrate, processes for its preparation, compositions containing the same and its therapeutic use as an anti-depressant. Excerpt(s): This invention relates to crystalline paroxetine hydrochloride, its preparation and its use as a therapeutic agent.... In this specification the compound of formula A is referred to by its generic name of paroxetine.... Because of its basicity, it is preferred that paroxetine is used as a therapeutic agent in the form of an acid addition salt. In Example 2 of U.S. Pat. No. 4,007,196, paroxetine is obtained as the free base and then converted to its maleic acid salt. Web site: http://www.delphion.com/details?pn=US04721723__ •

Aqueous process for manufacturing paroxetine solid dispersions Inventor(s): Chang; Sou-Chan (Westbury, NY), Kao; Huai-Hung D. (Syosset, NY), Hein, II; William A. (Hasbrouck Heights, NJ) Assignee(s): Endo Pharmaceuticals, Inc. (Chadds Ford, PA) Patent Number: 6,168,805 Date filed: May 7, 1998 Abstract: A process for preparing solid, amorphous paroxetine comprising: (A) mixing paroxetine free base or a pharmaceutically acceptable paroxetine salt with water and pharmaceutically acceptable polymer; and (B) drying to form a composition comprising amorphous paroxetine and polymer, eliminating the need for organic solvents common for the solvent process. The resultant amorphous solid paroxetine composition is free from crystalline form, and yet has good handling properties, making it suitable for pharmaceutical use in the traditional tablet dosage form. Excerpt(s): The present invention relates to processes for preparation of pharmaceutical compositions, the resultant compositions, and their use. Specifically, the present invention relates to pharmaceutical formulations of paroxetine, processes for the preparation of such formulations, pharmaceutical compositions containing the same and their use thereof in therapy.... The compound (-)-trans-4-((4'-fluorophenyl)3-(3'4'methylenedioxyphenoxymethyl)-piperid ine, commonly known as paroxetine, is a viscous oil and poorly water soluble drug which has been widely used pharmaceutical compositions, especially for depression.... U.S. Pat. No. 4,721,723 discloses crystalline paroxetine hydrochloride hemihydrate as a novel material with better handling properties than anhydrous paroxetine hydrochloride, a hygroscopic solid with poor handling properties. Web site: http://www.delphion.com/details?pn=US06168805__

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Method for drying anhydrous paroxetine hydrochloride Inventor(s): Kawata; Yoshihiro (Osaka, JP), Okatake; Mitsuru (Osaka, JP), Ishibashi; Taro (Osaka, JP) Assignee(s): Sumika Fine Chemicals Co., Ltd. (Osaka, JP) Patent Number: 6,541,637 Date filed: December 13, 1999

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Abstract: A process for drying paroxetine hydrochloride anhydrate comprising (A) reacting a paroxetine compound with hydrogen chloride in the presence of isopropyl alcohol and crystallizing the resulting product, to obtain paroxetine hydrochloride anhydrate, and drying the resulting paroxetine hydrochloride anhydrate at a temperature of not more than 60.degree. C. and under normal pressure or lower in an atmosphere which does not substantially contain moisture until the content of isopropyl alcohol attains to not more than 15% by weight; and (B) further drying the paroxetine hydrochloride anhydrate at a temperature of 80.degree. to 110.degree.C. in an atmosphere reduced to not more than 20 mm Hg until the content of isopropyl alcohol attains to not more than 5% by weight. According to the present invention, the amount of remaining isopropyl alcohol contained in the paroxetine hydrochloride anhydrate, crystallized in the presence of isopropyl alcohol, can be efficiently reduced in a short period of time without necessitating a large-scaled apparatus. Excerpt(s): The present invention relates to a process for drying paroxetine hydrochloride anhydrate. More specifically, the present invention relates to a process for drying paroxetine hydrochloride anhydrate to reduce the amount of remaining isopropyl alcohol.... Paroxetine hydrochlorides such as paroxetine hydrochloride anhydrate are useful compounds as antidepressants.... Conventionally, paroxetine hydrochloride anhydrate obtained by reacting paroxetine with hydrogen chloride in the presence of isopropyl alcohol contains isopropyl alcohol. Therefore, in order not to deform its crystal form, the paroxetine hydrochloride anhydrate is dried by a vacuum drying process employing a vacuum oven which is temperature-adjusted to a temperature lower than 80.degree. C. However, it has been difficult to sufficiently remove isopropyl alcohol contained in the paroxetine hydrochloride anhydrate by the vacuum drying process. Therefore, there is a defect in the process such that a long period of time of not less than about 100 hours is required to dry until the content of isopropyl alcohol attains to not more than 5% by weight. Web site: http://www.delphion.com/details?pn=US06541637__ •

Method of preparing optically pure precursors of paroxetine Inventor(s): Heefner; Donald L. (Hudson, MA), Gao; Yun (Framingham, MA), Zepp; Charles M. (Berlin, MA) Assignee(s): Sepracor, Inc. (Marlborough, MA) Patent Number: 5,258,517 Date filed: August 6, 1992 Abstract: A biocatalytic method of preparing optically pure precursors of paroxetine and a method of preparing paroxetine therefrom are disclosed. A racemic trans ester precursor compound of paroxetine is first prepared. The racemic trans ester precursor compound comprises a mixture of (3S,4R) and (3R,4S) enantiomers. The (3R,4S) enantiomer is hydrolyzed biocatalytically to the corresponding (3R,4S)-trans carboxylic acid or alternatively, the (3S,4R) enantiomer is biocatalytically hydrolyzed the to (3S,4R)trans carboxylic acid in a reaction catalyzed by a isolated enzyme or a microorganism. In the first instance, the unhydrolyzed (3S,4R) enantiomer is separated from the (3R,4S)trans carboxylic acid, whereas in the second instance the (3S,4R)-trans carboxylic acid is separated from the unhydrolyzed (3R,4S) enantiomer. The (3S,4R) enantiomer obtained following the selective hydrolysis is reduced to form a (-)-trans-(3S,4R) primary alcohol precursor of paroxetine. Paroxetine is then formed from the (-)-trans-(3S,4R) primary alcohol precursor.

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Excerpt(s): The present invention relates to a biocatalytic method of preparing optically pure precursors of paroxetine, and more particularly, it relates to an improved method of resolving a first racemic precursor of paroxetine into a second, optically pure precursor of paroxetine. Additionally, the present invention relates to a method of preparing paroxetine, an optically pure compound, from a racemic precursor.... The compounds of formula I have pharmacological properties that make them useful as antidepressants. One compound that has proved especially valuable is the serotonin (5-HT) uptake inhibitor paroxetine [R.sup.1.dbd.H, R.sup.2 =(1,3-benzodioxyl-5-yl), X.dbd.4-F], the pharmacologically active form of which is the (-)-trans isomer. The (-)-trans isomer (i.e., the active form) of paroxetine exhibits the (3S,4R) absolute stereoconfiguration according to Plenge et al. [J. Pharm. Pharmacol. 1987, 39: 877-882].... Paroxetine is prepared from the (3S,4R)-trans precursor compound of formula (II) making use of the procedures set out in U.S. Pat. No. 4,902,801 or U.S. Pat. No. 4,007,196. Web site: http://www.delphion.com/details?pn=US05258517__ •

Oral liquid compositions containing paroxetine resinate Inventor(s): Cooper; David (Welwyn Garden City, GB), Leonard; Graham Stanley (St Albans, GB) Assignee(s): SmithKline Beecham plc (Brentford, GB) Patent Number: 5,811,436 Date filed: August 1, 1996 Abstract: An oral liquid pharmaceutical composition comprising a paroxetine-Amberlite IRP88 complex. Excerpt(s): This application is a 371 of PCT/EP95/00319, filed Jan. 30, 1995, which claims priority to GB 9402029.4 filed Feb. 3, 1994.... The present invention relates to novel formulations and to the use of such a formulation in the treatment and/or prevention of certain disorders.... All paroxetine sold to date has been in the form of oral swallow tablets. Web site: http://www.delphion.com/details?pn=US05811436__

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Paroxetine hydrochloride form A Inventor(s): Ward; Neal (Crowborough, GB), Jacewicz; Victor Witold (Tunbridge Wells, GB) Assignee(s): SmithKline Beecham Corporation (Philadelphia, PA) Patent Number: 6,080,759 Date filed: September 2, 1997 Abstract: "Paroxetine hydrochloride (I) anhydrate free of bound propan-2-ol, and various forms thereof, are useful in the treatment of depression and other disorders for which administration of selective serotonin reuptake inhibitors are indicated." Excerpt(s): The present invention relates to novel compounds, to processes for preparing them and to their use in treating medical disorders.... U.S. Pat. No. 4, 721,723 (Beecham Group plc) describes paroxetine hydrochloride hemi-hydrate and its use in treating certain medical disorders. Example 8 in U.S. Pat. No. 4,721,723 describes the preparation

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of paroxetine hydrochloride anhydrate as platelets, by crystallization from a watercontaining solvent. This material is hereinafter referred to as Form Z. Subsequent repetition of the preparation described in Example 8 has failed to yield any type of paroxetine hydrochloride anhydrate, and there is no clear teaching elsewhere in the document of any alternative route or modification to the process which would generate the anhydrate.... Paroxetine hydrochloride anhydrate is also purported to be disclosed in the International Journal of Pharmaceutics 42, (1988) 135 to 143, published by Elsevier. The anhydrate is said to be produced by crystallizing paroxetine hydrochloride from anhydrous propan-2-ol. Subsequent repetition of this process has resulted in a propan-2ol solvate of paroxetine hydrochloride. That is to say that there is bound propan-2-ol in the product. This bound propan-2-ol cannot be removed by conventional drying techniques such as vacuum oven drying. Web site: http://www.delphion.com/details?pn=US06080759__ •

Paroxetine hydrochloride form A or C Inventor(s): Ward; Neal (Crowborough, GB), Jacewicz; Victor Witold (Turnbridge Wells, GB) Assignee(s): SmithKline Beecham Corporation (Philadelphia, PA) Patent Number: 6,133,289 Date filed: September 2, 1997 Abstract: Invented are methods of treatment using novel forms of paroxetine hydrochloride anhydrate. Excerpt(s): The present invention relates to novel compounds, to processes for preparing them and to their use in treating medical disorders.... U.S. Pat. No. 4,721,723 (Beecham Group plc) describes paroxetine hydrochloride hemi-hydrate and its use in treating certain medical disorders. Example 8 in U.S. Pat. No. 4,721,723 describes the preparation of paroxetine hydrochloride anhydrate as platelets, by crystallization from a watercontaining solvent. This material is hereinafter referred to as Form Z. Subsequent repetition of the preparation described in Example 8 has failed to yield any type of paroxetine hydrochloride anhydrate, and there is no clear teaching elsewhere in the document of any alternative route or modification to the process which would generate the anhydrate.... Paroxetine hydrochloride anhydrate is also purported to be disclosed in the International Journal of Pharmaceutics 42, (1988) 135 to 143, published by Elsevier. The anhydrate is said to produced by crystallizing paroxetine hydrochloride from anhydrous propan-2-ol. Subsequent repetition of this process has resulted in a propan-2ol solvate of paroxetine hydrochloride. That is to say that there is bound propan-2-ol in the product. This bound propan-2-ol cannot be removed by conventional drying techniques such as vacuum oven drying. Web site: http://www.delphion.com/details?pn=US06133289__

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Paroxetine in the treatment of depression associated with withdrawal from heroin abuse and post-traumatic stress disorder Inventor(s): Gleason; Maurice (Newbury, GB) Assignee(s): SmithKline Beecham plc (Brentford, GB) Patent Number: 6,121,291 Date filed: February 11, 1999 Abstract: This invention relates to the use of paroxetine or a pharmaceutically acceptable salt thereof for the treatment of post-traumatic stress disorder and depression associated with withdrawal from heroin abuse. Excerpt(s): The present invention relates to the treatment and/or prevention of specific types of depression.... U.S. Pat. No. 4,007,196 discloses the compound, (-)-trans-4-(4'fluorophenyl)-3-(3'4'-methylenedioxy-phenoxymethyl) piperidine, and, in Example 2, a process by which it can be prepared. The compound, which is referred to herein by its common name, paroxetine, is described in the patent as an inhibitor of 5hydroxytryptamine uptake and, therefore, is of use in the treatment of depression in general.... It has now been surprisingly discovered that paroxetine has particularly effective therapeutic utility for treating and/or preventing specific types of depression. Web site: http://www.delphion.com/details?pn=US06121291__

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Paroxetine maleate polymorph and pharmaceutical compositions containing it Inventor(s): Molins Grau; Elias (Sant Feliu de Llobregat, ES), Bosch Llado; Jordi (Gerona, ES), Stampa Diez del Corral; Alberto (Barcelona, ES), Onrubia Miguel; Maria del Carmen (Barcelona, ES) Assignee(s): Medichem, S.A. (Barcelona, ES) Patent Number: 6,440,459 Date filed: January 4, 2001 Abstract: The form B of paroxetine maleate polymorph is characterized by determined data of X ray diffraction: it has a chemical stability which is superior to that of the form A of paroxetine maleate. This superior stability enables to use the new polymorph for the fabrication of medicaments intended to the treatment of troubles related to dysfunctions of the central nervous system. The process for producing the paroxetine maleate comprises the preparation of paroxetine maleate solution and a consequent precipitation. Excerpt(s): The present invention relates to a paroxetine maleate polymorph and to pharmaceutical formulations containing it; it also relates to the use and to a process for the preparation thereof. This polymorph is crystalline and is used as stable active principle in the preparation of pharmaceutical formulations indicated for disorders deriving from dysfunction of the central nervous system.... is described, together with a process for the preparation thereof, in Example 2 of U.S. Pat. No. 4,007,196 and in the same example of the corresponding Spanish patent of introduction ES-A-504997.... It is well known that paroxetine and the pharmaceutically acceptable salts thereof have a recognized activity as agents for the treatment of disorders related with dysfunction of the central nervous system, mainly, although not only, as antidepressants. Web site: http://www.delphion.com/details?pn=US06440459__

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Paroxetine tablets and process to prepare them Inventor(s): Doughty; David George (Welwyn Garden City, GB), Pathak; Ram Dutta (Epsom Downs, GB) Assignee(s): SmithKline Beecham p.l.c. (Brentford, GB) Patent Number: 6,113,944 Date filed: June 30, 1998 Abstract: Invented is a novel pharmaceutical composition containing Paroxetine. Excerpt(s): The present invention relates to novel formulations and to the use of the formulation in the treatment and/or prevention of certain disorders.... This compound has been approved for human use and is being sold in many countries around the world as an anti-depressant agent.... It has been noticed that tablets of paroxetine often develop a pink hue which is highly undesirable. Web site: http://www.delphion.com/details?pn=US06113944__

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Process for manufacturing paroxetine solid dispersions Inventor(s): Teleha; Christopher A. (Bear, DE), Chang; Sou-Chan (Westbury, NY), Krape; Philip J. (Wilmington, DE), Hein, II; William A. (Hasbrouck Heights, NJ) Assignee(s): Endo Pharmaceuticals Inc. (Chadds Ford, PA) Patent Number: 5,955,475 Date filed: June 30, 1997 Abstract: Solid dispersions of poorly soluble drugs are disclosed which are prepared using a solvent or fusion process. Such dispersions are manufactured with the free base of the drug, specifically paroxetine free base, an oil, allowing for a low temperature for the fusion process, decreased organic solvent volumes for the solvent process and the formation of a paroxetine salt during the solid dispersion manufacture process. Excerpt(s): The present invention relates to the field of solid dispersions of poorly water soluble drugs, to processes for their preparation and their use in pharmaceutical compositions. Specifically, the present invention relates to solid dispersions resulting from fusion or solvent methods for the incorporation of poorly water soluble drugs into pharmaceutically acceptable carriers. More specifically, the invention relates to the solid dispersions of paroxetine, processes for the preparation of such solid dispersions, pharmaceutical compositions containing the same and their use thereof in therapy.... The compound (-)-trans-4-((4'-fluorophenyl)3-(3'4'-methylenedioxyphenoxymethyl)piperid ine, commonly known as paroxetine, is a viscous oil and poorly water soluble drug with a commercial need for useful pharmaceutical compositions. A solid dispersion of paroxetine or its acid addition salt, never described before now in the literature, would provide a solid product on a commercial scale with good handling qualities and physiological acceptability without the need or expense to manufacture crystalline materials.... Pharmaceutical compositions with good dissolution and bioavailability can be formulated from solid dispersions of pharmaceutically active ingredients. Advantages claimed for pharmaceutical solid dispersions include potential use in controlled release formulations, stabilizing the drug from polymorphic conversions, improving poor handling properties of drug substances and protecting certain drugs against decomposition during administration. Solid dispersions of pharmaceutically active ingredients can be formed from a number of pharmaceutically

Patents 51

acceptable carriers. U.S. Pat. No. 4,933,360 describes a novel process and product comprising chlorthalidone as the pharmaceutical active ingredient and polyvinylpyrrolidone (PVP) as the pharmaceutically acceptable carrier. The techniques have been described in general by W. L. Chiou et al., J. Pharm. Sci. 60(28)(1971) and S. Riegelman et al, U.S. Pat. No. 4,151,273. As defined in the Chiou article the term "solid state dispersion" means a dispersion of one or more active ingredients in an inert carrier or matrix in a solid state prepared by a melting (fusion), solvent, or combined meltsolvent method. The dispersion of an active ingredient in a solid carrier or diluent by traditional mechanical mixing is not included within the definition of this term. Web site: http://www.delphion.com/details?pn=US05955475__ •

Process for the production of paroxetine Inventor(s): Donnarumma; Maria (Latina, IT), Rossi; Renzo (Pisa, IT), Turchetta; Stefano (Rome, IT) Assignee(s): Recordati S.A. Chemical and Pharmaceutical Company (CH) Patent Number: 6,583,287 Date filed: July 30, 2001 Abstract: A process for the production of paroxetine is described, wherein N-substituted derivatives of 4-(p-fluorophenyl)-3-hydroxymethyl-1,2,3,6-tetrahydropyridine are treated according to the following sequence of reactions: (a) hydrogenation catalyzed by transition metal complexes with chiral diphosphinic ligands; (b) --OH derivatisation and nucleophilic substitution, the substituent being sesamol; (c) N-dealkylation. The process is highly stereospecific and brings about the formation of intermediates enriched with the desired isomeric components, which are converted into paroxetine in quantitative yields. Excerpt(s): The field of the present invention is the synthesis of optically active compounds. A highly stereospecific process for synthesis of paroxetine is described herein.... The molecule of formula (I) contains two chiral centres on the piperidinic ring, in position 3 and 4, respectively. Of the four possible isomers, only the isomer having absolute configuration 3S, 4R, known as 4R-trans-4-(p-fluorophenyl-3-{[3,4(methylenedioxy)phenoxy]methyl}piperidi ne, is pharmacologically active. Therefore, the processes for synthesis of paroxetine must result in the formation of the 4-(pfluorophenyl-3-{[3,4-(methylenedioxy)phenoxy]methyl}piperidinic structure, exclusively in the aforesaid conformation, 3S, 4R (or 4R-trans).... where R represents an alkyl group. Starting from this intermediate, the product of formula (I) is obtained by: (i) reduction of the piperidinic double bond, (ii) alkylation of the oxygen of the hydroxymethyl group, and (iii) removal of the alkyl group R bound to the nitrogen. In order to obtain the product (I) with the pharmacologically active conformation, the process requires the isolation of specific isomers from the corresponding racemic mixtures and the treatment of the same until obtaining derivative (I) with the desired conformation. Web site: http://www.delphion.com/details?pn=US06583287__

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Use of paroxetine for the treatment of senile dementia, bulimia, migraine or anorexia Inventor(s): Johnson; Anthony M. (Welwyn, GB2) Assignee(s): Beecham Group, p.l.c. (New Horizons Court, GB2) Patent Number: 5,371,092 Date filed: May 21, 1993 Abstract: The method of using paroxetine or a pharmaceutically acceptable salt thereof for the treatment of senile dementia. Excerpt(s): The present invention relates to a method for the treatment of senile dementia, bulimia, migraine or anorexia and to a compound for use in such methods.... U.S. Pat. No. 4 007 196 discloses the compound, (-)-trans-4-(4'-fluorophenyl)-3-(3'4'methylenedioxyphenoxymethyl)piperidi ne, and, in Example 2, a process by which it can be prepared. The compound, which is referred to herein by its common name, paroxetine, is described in the patent as an inhibitor of 5-hydroxytryptamine uptake and, therefore, is of use in the treatment of depression. The patent also mentions that paroxetine is useful in the treatment of Parkinson's disease.... It has now been discovered that paroxetine also has potential therapeutic utility for treating senile dementia, bulimia, migraine or anorexia. Web site: http://www.delphion.com/details?pn=US05371092__

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Useful form of anhydrous paroxetine hydrochloride Inventor(s): Weeratunga; Gamini (Brantford, CA), Rey; Allan (Brantford, CA), Murthy; K. S. Keshava (Brantford, CA) Assignee(s): Brantford Chemicals Inc. (Brantford, CA) Patent Number: 6,436,956 Date filed: November 24, 1997 Abstract: Paroxetine hydrochloride anhydrous designated as Form IV having at least one, some or all of the following characteristics:a) Infrared spectra as shown in FIG. 1 and 2,b) A X-ray powder diffraction pattern as shown in Schedule "C",c) A melting point of between about 80.degree.0 C. to about 95.degree. C. Excerpt(s): This invention relates to a new and useful form of paroxetine hydrochloride (anhydrous) and its preparation thereof.... Canadian Letter Patent 1,287,060 describes two distinct forms of paroxetine hydrochloride viz., an anhydrous form of paroxetine hydrochloride and the hemihydrate form of paroxetine hydrochloride (paroxetine hydrochloride_H.sub.2 O). The existence of these forms is confirmed in the International Journal of Pharmaceutics, 42, pp. 135-143 and Analytical Proceedings, 25, pp. 305-306, both published in 1988. Canadian Patent Applications Serial No. 2,168,829 (1996) and 2,187,128 (Brantford Chemicals Inc.) (1996) purport to describe several new polymorphs of paroxetine hydrochloride anhydrate.... The two forms described in Canadian Letter Patent 1,287,060, International Journal of Pharmaceutics, 42, pp. 135-143 (1988), and Analytical Proceedings, 25, pp. 305-306 (1988) have been known for a substantial period of time, particularly the anhydrous form, which has a melting point of about 118.degree. C. and which is known to be hygroscopic making this material difficult to handle. Coupled with this is the fact that the said anhydrous material is also light and fluffy, which further compounds the problems of handling (filtration and drying) and formulating the active into the final dosage form.

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Web site: http://www.delphion.com/details?pn=US06436956__

Patent Applications on Paxil As of December 2000, U.S. patent applications are open to public viewing.10 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to Paxil: •

Formulations comprising dissolved paroxetine Inventor(s): Leonard, Graham Stanley; (St Albans, GB), Al-Ghazawi, Ahmad Khalaf AlDeeb; (Waltham, GB) Correspondence: GLAXOSMITHKLINE; Corporate Intellectual Property - UW2220; P.O. Box 1539; King of Prussia; PA; 19406-0939; US Patent Application Number: 20020032220 Date filed: August 9, 2001 Abstract: Pharmaceutical formulations of paroxetine are provided in which the paroxetine is in solution in a solid, semi-solid or liquid carrier. The solutions are used to fill capsules, or self-supporting solid solutions are shaped into solid dosage forms such as tablets or pellets. Also disclosed are novel liquid formulations in which a solubilising agent is used to solubilise paroxetine in oils and/or lipids, and methods of avoiding other paroxetine forms converting to the hemihydrate, by use of anhydrous or hydrophobic carriers or excipients. Excerpt(s): The present invention relates to novel formulations of a pharmaceutically active compound, and to the use of the formulations in therapy. In particular this invention is concerned with new formulations of the anti-depressant paroxetine.... Pharmaceutical products with antidepressant and anti-Parkinson properties are described in U.S. Pat. No. 3,912,743 and U.S. Pat. No. 4,007,196. An especially important compound among those disclosed is paroxetine, the (-)trans isomer of 4-(4'fluorophenyl)-3-(3',4'-methylenedioxy-phenoxymethyl)-piperidine. Paroxetine hydrochloride hemihydrate is used in therapy for the treatment and prophylaxis of inter alia depression, obsessive compulsive disorder (OCD) and panic.... Paroxetine hydrochloride hemihydrate is described in EP-A-0223403 of Beecham Group and paroxetine hydrochloride anhydrate Forms A, B, C and D are described in WO 96/24595 of SmithKline Beecham plc. All solid oral dosage forms of paroxetine hydrochloride sold to date have been in the form of oral swallow tablets, containing the hemihydrate. WO 95/16448 discloses that paroxetine is likely to develop a pink colour unless it is formulated into tablets using a formulation process in which water is absent, such as dry direct compression of paroxetine or dry granulation of paroxetine followed by compression into tablets. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

10

This has been a common practice outside the United States prior to December 2000.

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Formulations, tablets of paroxetine and process to prepare them Inventor(s): Doughty, David George; (Welwyn Garden City, GB), Pathak, Ram Dutta; (Epsom Downs, GB) Correspondence: GLAXOSMITHKLINE; Corporate Intellectual Property - UW2220; P.O. Box 1539; King of Prussia; PA; 19406-0939; US Patent Application Number: 20030091628 Date filed: November 5, 2002 Abstract: Paroxetine which is formulated into tablets using a formulation process in which water is absent. Excerpt(s): The present invention relates to novel formulations and to the use of the formulation in the treatment and/or prevention of certain disorders.... This compound has been approved for human use and is being sold in many countries around the world as an anti-depressant agent.... It has been noticed that tablets of paroxetine often develop a pink hue which is highly undesirable. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Liquid for oral administration comprising paroxetine Inventor(s): Sherman, Bernard Charles; (Toronto, CA) Correspondence: NIXON & VANDERHYE P.C. 8th Floor; 1100 North Glebe Rd. Arlington; VA; 22201-4714; US Patent Application Number: 20030078285 Date filed: October 4, 2002 Abstract: An oral liquid pharmaceutical composition comprising paroxetine or a salt thereof and a basic compound which imparts a pH of above 7 to the composition. Excerpt(s): Paroxetine is a compound useful as an antidepressant and is disclosed in U.S. Pat. No. 4,007,196.... Compositions comprising paroxetine as the hydrochloride salt are sold in the United States and elsewhere under the brandname Paxil.TM.. Paxil.TM. is available as tablets for oral administration, and also as a suspension for oral administration in strengths of 10 mg per 5 mL; i.e. each 5 mL contains paroxetine hcl 11.1 mg, which is equivalent to paroxetine 10 mg.... It is difficult to formulate a suitable oral liquid comprising paroxetine or a paroxetine salt, because paroxetine has a very bitter taste. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method of producing amorphous paroxetine hydrochloride Inventor(s): Matsumura, Yasushi; (Kanagawa, JP), Okazoe, Takashi; (Kanagawa, JP), Wang, Shu-Zhong; (Kanagawa, JP) Correspondence: OBLON SPIVAK MCCLELLAND MAIER & NEUSTADT PC; FOURTH FLOOR; 1755 JEFFERSON DAVIS HIGHWAY; ARLINGTON; VA; 22202; US Patent Application Number: 20010021776 Date filed: May 4, 2001

Patents 55

Abstract: A method of producing amorphous paroxetine hydrochloride, which comprises converting paroxetine or its lower alkanoic acid salt into paroxetine hydrochloride and then spray drying a solution of the hydrochloride. Excerpt(s): The present invention relates to a method of producing paroxetine hydrochloride which has an inhibitory action on 5-hydroxytriptamine (5-HT) and is useful as a therapeutic agent for various diseases such as depression and Parkinson's diseases.... Paroxetine hydrochloride, i.e. (3S,4R)-3-[5-(1,3-dioxaindanyl)oxymethyl]-4(p-fluorophenyl)piperidine hydrochloride, has been obtainable in the crystalline form, and hemihydrated paroxetine hydrochloride is also known in the crystalline form (U.S. Pat. No. 4,007,196, and Japanese Examined Patent Publication JP-B-6-47587). However, because of their crystallinity, they are medicines which are slowly absorbed into the body.... To solve the problem, the present invention provides a method of producing amorphous paroxetine hydrochloride which is generally easy to absorb. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

N-formyl derivatives of paroxetine Inventor(s): Picha, Frantisek; (Brno, CZ), Peters, Theodorus H.A. (Nijmegen, NL), Hoorn, Hans J. (Nijmegen, NL) Correspondence: FLESHNER & KIM, LLP; P.O. BOX 221200; CHANTILLY; VA; 20153; US Patent Application Number: 20030125560 Date filed: October 21, 2002 Abstract: A compound or composition comprising N-formyl paroxetine of formula (1) is useful as a pharmaceutical and as a synthetic intermediate. The N-formyl paroxetine can be an impurity in paroxetine substances and methods of assaying for such an impurity are also useful. 1 Excerpt(s): The present invention relates to N-formyl paroxetine compounds, to compositions containing the same and to uses thereof as an intermediate, as a reference marker or standard, and/or as a pharmaceutical active ingredient.... U.S. Pat. No. 4,723,721 and EP 223403 describe crystalline paroxetine hydrochloride hemihydrate. This particular form of paroxetine is the active ingredient in a commercial pharmaceutical tablet sold/made by SmithKline Beecham under such brand names as PAXIL.RTM. and SEROXAT.TM..... Pharmaceutical products are regulated in most countries by a government agency. For example, the U.S. Food & Drug Administration (FDA) generally requires an applicant to show safety and efficacy of the pharmaceutical product during the approval/review phase and requires monitoring of the safety of the drug post-approval. Similar requirements exist in many European countries and elsewhere in the world. In order to satisfy safety concerns, the regulatory agencies generally require a manufacturing specification that sets the maximum amount of each identified impurity as well as the maximum amount for all remaining unidentified impurities. Once approved, each batch or lot of the pharmaceutical product is tested to insure that the specification is met. Further, stability testing is performed on the pharmaceutical product in order to show that the composition does not substantially or materially change over time; i.e. over its indicated shelf-life. Good practice warrants keeping a sample from each batch which has been released to the public so that the stability of the product can be monitored over time and any defect uncovered and corrective action can be taken as appropriate.

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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Optically pure paroxetine precursors Inventor(s): de Gonzalo Calvo, Gonzalo; (Oviedo, ES), Brieva Collado, Rosario; (Oviedo, ES), Gotor Santamaria, Vicente; (Oviedo, ES), Sanchez Pedregal, Victor; (Llanera, ES), Bayod Jasanada, Miguel; (LLanera, ES) Correspondence: MICHAELSON AND WALLACE; PARKWAY 109 OFFICE CENTER; 328 NEWMAN SPRINGS RD; P O BOX 8489; RED BANK; NJ; 07701 Patent Application Number: 20030018048 Date filed: July 10, 2002 Abstract: A biocatalytic process to obtain optically enriched derivatives of trans-4-(4fluorophenyl)-3-hydroxymethylpiperidines, based on the enzymatic resolution of racemic precursors of formula III (where R.sup.3 is preferably phenyl or benzyl) by acylation of the hydroxyl group. Depending on the enzyme and the reaction conditions, either of the two enantiomers may be obtained with high enantiomeric purity. These compounds are important intermediates in the synthesis of the paroxetine antidepressive agent. 1 Excerpt(s): Paroxetine is an arylpiperidine acting as a selective inhibitor for serotonin (5HT) re-uptake. Mainly, this compound has anti-depressive and anti-parkinsonian activity. Only the trans-(-) isomer, with absolute configuration (3S, 4R) may be used as a drug.... Another object of the invention are the new compounds obtained, III, IV and V both in the racemic and enatiomerically enriched forms, suitable for the synthesis of paroxetine, as well as their preparation processes.... In U.S. Pat. Nos. 4,007,196 and 4,902,801, said piperidinecarbinol II compound is firstly obtained as a racemic mixture and then resolved in its enantiomers by conventional methods, such as the crystallisation of its diastereoisomer salts with chiral acids, like (+)-tartaric, (+)-2'nitrolartranylic or (-)-di-P-toluyltartaric. The drawback of this process is that crystallisation is cumbersome and relatively expensive. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Optimized procedures for the manufacture of paroxetine salts Inventor(s): Wojcik, Bryant; (LaGrange, IL), Ronsen, Bruce; (River Forest, IL), Upadhyaya, Subhash P. (Chicago, IL) Correspondence: Bruce D. Grant; Morrison & Foerster LLP; Suite 500; 3811 Valley Centre Drive; San Diego; CA; 92130; US Patent Application Number: 20030032809 Date filed: April 25, 2002 Abstract: Described herein are methods for manufacturing amorphous paroxetine hydrochloride by mixing a carboxylic acid salt of paroxetine with hydrogen chloride and isolating the amorphous paroxetine hydrochloride. Also described herein are methods for manufacturing substantially pure paroxetine free base and methods for obtaining paroxetine salts such as paroxetine acetate, paroxetine trifluoroacetate, and paroxetine formate. Also described are methods for preparing paroxetine carbonate,

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paroxetine phosphate, paroxetine sulfate, and analogous salts thereof. The paroxetine salts may be formulated for the treatment of medical disorders as described. Excerpt(s): This application claims the benefit of the Apr. 25, 2001 filing date of U.S. application Ser. No. 60/286,590, the May 11, 2001 filing date of U.S. application Ser. No. 60/290,411, and the Jun. 1, 2001 filing date of U.S. application Ser. No. 60/295,471, each of which is entitled "Paroxetine Salts And Processes For The Manufacture Of Paroxetine Salts" and names S. Upadhyaya and B. Ronsen as inventors. This application also claims the benefit of the Nov. 20, 2001 filing date for U.S. application Ser. No. 60/333,530, which is entitled "Optimized Procedures for the Manufacture of Paroxetine Salts" and names S. Upadhyaya and B. Ronsen as inventors. Each of these applications is incorporated herein by reference in its entirety.... The invention relates to a class of compounds known as paroxetines. In particular, disclosed herein are processes for purifying paroxetine free base and preparing paroxetine salts.... Processes for manufacturing substantially pure paroxetine salts are required for producing pharmaceuticals for treating these medical conditions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Paroxetine compositions Inventor(s): Ward, Neal; (East Sussex, GB), Craig, Andrew Simon; (Kent, GB) Correspondence: GLAXOSMITHKLINE; Corporate Intellectual Property - UW2220; P.O. Box 1539; King of Prussia; PA; 19406-0939; US Patent Application Number: 20020123511 Date filed: April 29, 2002 Abstract: Paroxetine is adsorbed on a carrier to form a free-flowing powder useful for capsule filling or for tablet formation; and used in therapy to treat depression. Excerpt(s): The present invention relates to new formulations of a pharmaceutically active compound, and in particular to a novel formulation of paroxetine.... Pharmaceutical products with antidepressant and anti-Parkinson properties are described in U.S. Pat. No. 3,912,743 and U.S. Pat. No. 4,007,196. An especially important compound among those disclosed is paroxetine, the (-)trans isomer of 4-(4'fluorophenyl)-3-(3',4'methylenedioxy-phenoxymethyl)-piperidine.... In the literature this compound is usually isolated as an acid salt, especially the hydrochloride. Paroxetine is approved for human use as the hydrochloride salt, and has been proposed for the treatment and prophylaxis of inter alia depression, obsessive compulsive disorder (OCD) and panic. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Paroxetine compositions and processes for making the same Inventor(s): Dalen, Frans van; (Nijmegen, NL), Platteeuw, Johannes J. ('s-Hertogenbosch, NL), Picha, Frantisek; (Brno, CZ), Peters, Theodorus H. A. (Arnhem, NL), Lemmens, Jacobus M. (Mook, NL) Correspondence: SYNTHON PHARMACEUTICALS, LTD. PATENT DEPT. P.O. BOX 161; CATHARPIN; VA; 20143; US Patent Application Number: 20020065301 Date filed: August 28, 2001 Abstract: Paroxetine salt compositions having improved stability are formed by controlling the pH to 6.5 or less. The compositions can be made with the aide of water without significant coloration problems. The paroxetine salts include paroxetine hydrochloride salts but preferably use paroxetine sulfonate salts such as paroxetine methane sulfonate. Excerpt(s): This application claims the benefit of priority under 35 U.S.C..sctn.119(e) from prior U.S. provisional application serial No. 60/228,110 filed Aug. 28, 2000 and from prior U.S. provisional application serial No. 60/234,936 filed Sep. 26, 2000: the entire contents of each of the aforementioned provisional applications being incorporated herein by reference.... The present invention relates to a paroxetine compositions, especially pharmaceutical formulations and dosage forms, and to processes of manufacturing the same.... Paroxetine has been approved for treating, inter alia, depression in humans and is being marketed around the world under such brand names as Paxil.RTM. (SmithKline Beecham) and Seroxat. Dosage forms thus far include immediate release tablets, extended release tablets, capsules and suspensions. The active substance in all commercial forms thus far has been paroxetine hydrochloride and specifically with regard to tablets and other solid forms the active has been paroxetine hydrochloride hemihydrate as disclosed in U.S. Pat. No. 4,721,723 and EP 223403. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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PAROXETINE CONTROLLED RELEASE COMPOSITIONS Inventor(s): LEONARD, GRAHAM STANLEY; (HERTFORDSHIRE, GB), ELDER, DAVID PHILIP; (HERTFORDSHIRE, GB) Correspondence: SMITHKLINE BEECHAM CORPORATION; CORPORATE INTELLECTUAL PROPERTY UW2220; P O BOX 1539; KING OF PRUSSIA; PA; 194060939 Patent Application Number: 20020028242 Date filed: September 9, 1999 Abstract: A controlled release or delayed release formulation contains a selective serotonin reuptake inhibitor (SSRI) such as paroxetine. Excerpt(s): The present invention relates to a novel formulation containing paroxetine or a pharmaceutically acceptable salt thereof, and to its use in the treatment and/or prophylaxis of certain disorders.... U.S. Pat. No. 4,007,196 describes inter alia a compound which is commonly known as paroxetine. This compound is a Selective Serotonin Reuptake Inhibitor (SSRI) and is currently marketed world-wide for the treatment and/or prophylaxis of depression.... The current formulation which is the only marketed formulation of paroxetine hydrochloride is a swallow tablet.

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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Paroxetine maleate Inventor(s): Man, John; (Sidcup, GB), Jones, David Alan; (Sevenoaks, GB), Jacewicz, Victor Witold; (Tonbridge Wells, GB) Correspondence: SMITHKLINE BEECHAM CORPORATION; CORPORATE INTELLECTUAL PROPERTY-US, UW2220; P. O. BOX 1539; KING OF PRUSSIA; PA; 19406-0939; US Patent Application Number: 20030028027 Date filed: June 17, 2002 Abstract: Paroxetine maleate and its preparation and use in the treatment and prevention of inter alia depression. Excerpt(s): The present invention relates to a novel compound, to processes for preparing it and to its use in treating medical disorders.... Pharmaceutical products with antidepressant and anti-Parkinson properties are described in U.S. Pat. No. 3,912,743 and U.S. Pat. No. 4,007,196. An especially important compound among those disclosed is paroxetine, the (-)trans isomer of 4-(4'-fluorophenyl)-3-(3',4'-methylenedioxyphenoxymethyl)-piperidine. This compound is used in therapy as the hydrochloride salt for the treatment and prophylaxis of inter alia depression, obsessive compulsive disorder (OCD) and panic.... Example 2 of U.S. Pat. No. 4,007,196 describes the preparation of paroxetine by demethylation of the N-methyl derivative. Paroxetine free base is isolated as an oil by evaporation of a benzene solution. The free base is dissolved in ether and treated with a solution of maleic acid in ethyl ether to form a crystalline product, which is recrystallised from 99% ethanol-ether to give a maleate salt melting 136-8.degree. C. Apart from the melting point, there is no characterizing data that allows an unambiguous assignment of structure. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Paroxetine tablets & capsules Inventor(s): Kota, Venkata R. (Union, NJ), Ronsen, Bruce; (River Forest, IL), Sadhale, Yogesh; (Greenville, NC) Correspondence: Bruce D. Grant; Morrison & Foerster LLP; Suite 500; 3811 Valley Centre Drive; San Diego; CA; 92130; US Patent Application Number: 20030008902 Date filed: June 21, 2002 Abstract: Methods for preparing a wet granule formulation of paroxetine hydrochloride are disclosed. The formulations are suitable for tabletting and capsulation. Excerpt(s): This application is a divisional of U.S. application Ser. No. 09/626,941, filed Jul. 27, 2000, which is incorporated herein by reference.... The invention relates to wet granulation formulations of paroxetine hydrochloride. By addition of an acidulent and a water dispersible polymer, a sufficient degree of solubility for paroxetine hydrochloride amorphous in aqueous solution can be achieved to permit a practical wet granulation method to be performed. These formulations are particularly useful for preparing capsules and tablets.... Wet granulation is the oldest and most conventional method of

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making tablets. This highly versatile process has been extensively reviewed by Record (Int. J. Pharm. Prod. Dev., 1:32-39, 1980), Kristensen and Schaefer (Drug Dev. Ind. Pharm., 13 (4 and 5):803-872, 1987) and Capes (Handbook of Powder Technology, J. C. Williams and T. Allen, Eds., Elsevier, Amsterdam, 1980). Pharmaceutical Dosage Forms: Tablets, Volume 1, H. A. Lieberman, L. Lachman and J. B. Schwartz, Eds., 1989, lists some advantages of the wet granulation method. These are improvement in the cohesiveness and compressibility of powders, enhancement of the flow properties of the drug and/or excipients, improvement in the content uniformity of the blend, especially with low dose drugs, and improvement in the aesthetic elegance of the formulation by preventing problems such as non-uniform color distribution and/or color migration. Wet granulation has some disadvantages, such as the need for large number of processing steps which are time-consuming, the need for a number of pieces of expensive equipment, and slightly larger material losses. However, the superior quality of the final product and the versatility of the process normally outweighs these disadvantages. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Preparation of paroxetine involving novel intermediates Inventor(s): Avrutov, Ilya; (Bat Hefer, IL), Pilarski, Gideon; (Holon, IL) Correspondence: KENYON & KENYON; ONE BROADWAY; NEW YORK; NY; 10004; US Patent Application Number: 20030166938 Date filed: May 1, 2002 Abstract: Disclosed are processes for preparing novel carbamate intermediates of paroxetine comprising dealkylating N-alkylparoxetine by reaction thereof with a haloalkyl ester of a haloformic acid, in a suitable organic solvent. Also disclosed are processes for preparing paroxetine comprising hydrolyzing the novel carbamate intermediates in a suitable solvent. Paroxetine prepared by the above processes can be neutralized with hydrogen chloride and crystallized as paroxetine hydrochloride anhydrous, hemihydrate or as a solvate of isopropanol. The invention is further directed to the novel carbamate intermediates formed by the disclosed processes. Excerpt(s): This application claims the benefit of provisional application Serial No. 60/360,760, filed Mar. 1, 2002, which is incorporated herein by reference.... The present invention relates to processes for the synthesis of intermediates useful in preparing paroxetine (PRX); processes for preparing paroxetine using such intermediates; and, to intermediates of the disclosed processes. More particularly, the present invention relates to a novel process for the preparation of paroxetine by dealkylation of Nalkylparoxetine, such as N-methylparoxetine (Me-PRX), and to novel intermediates of this process.... In the process disclosed in the '196 patent, Me-PRX is demethylated by reaction with phenylchloroformate in methylene chloride to form the corresponding phenyl carbamate intermediate. The phenyl carbamate intermediate is hydrolyzed to yield paroxetine by refluxing in benzene with potassium hydroxide and methyl cellosolve for four hours. Among the disadvantages of this process are the low conversion of Me-PRX to the phenyl carbamate, resulting in low yields of paroxetine. This process also results in large quantities of phenol as an undesirable by-product. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Process for preparing paroxetine HCl which limits formation of pink colored compounds Inventor(s): Pilarsky, Gideon; (Holon, IL), Avrutov, IIya; (Bat Hefer, IL) Correspondence: KENYON & KENYON; ONE BROADWAY; NEW YORK; NY; 10004; US Patent Application Number: 20030083501 Date filed: June 14, 2002 Abstract: The present invention provides a process for preparing paroxetine HCl from paroxetine base which provides paroxetine HCl substantially free of pink-colored compounds or an impurity identified by an HPLC RRT of about 1.5. The processes of the present invention utilize a buffer, a molar ratio of HCl to paroxetine base of less than one, and crystallize/recrystallize in the presence of an effective amount of an antioxidants. A preferred way to create a buffer is by using ammonium chloride. A preferred anti-oxidant is ascorbic acid.The present invention also provides for recrystalizing paroxetine HCl prepared by the above methods or any other methods in the presence of an effective amount of an anti-oxidant such as ascorbic acid. A preferred solvent system for recrystallization is a mixture of acetone and methanol.Processes of the present invention can combine these various features. Excerpt(s): This application claims priority to provisional applications Serial No. 60/298,603, filed Jun. 14, 2001; Serial No. 60/326,993, filed Oct. 5, 2001 and Serial No. 60/346,048, filed Jan. 4, 2002, the contents of which are incorporated herein by reference.... The present invention relates to paroxetine, more particularly, a process for the preparation of paroxetine HCl.... Paroxetine, disclosed in U.S. Pat. No. 4,007,196, is prescribed for the treatment of, inter alia, depression, Parkinson's disease, anxiety disorders, obsessive-compulsive disorders, panic disorder and post-traumatic stress disorder. Other syndromes such as pre-menstrual syndrome (PMS) can also be treated with paroxetine. Paroxetine is marketed as Paxil.RTM. in dosage forms containing about 10-40 mg of paroxetine HCl. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Process for producing paroxetine Inventor(s): Wang, Shu-zhong; (Yokohama-shi, JP), Matsumura, Yasushi; (Yokohamashi, JP) Correspondence: OBLON SPIVAK MCCLELLAND MAIER & NEUSTADT PC; FOURTH FLOOR; 1755 JEFFERSON DAVIS HIGHWAY; ARLINGTON; VA; 22202; US Patent Application Number: 20020198387 Date filed: May 30, 2002 Abstract: A process for producing a paroxetine represented by the following formula (4), which comprises reacting an N-alkylpiperidine represented by the following general formula (1) with a haloformic acid ester represented by the general formula (2) to prepare an alkoxycarbonylpiperidine represented by the general formula (3), and hydrolyzing the alkoxycarbonylpiperidine under alkaline conditions: 1wherein each of R.sup.1 and R.sup.2 is a lower alkyl group, a lower cycloalkyl group, an aralkyl group or C.sub.mF.sub.2m+1 (wherein m is an integer of from 1 to 6), and X is a halogen atom.

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Excerpt(s): The present invention relates to a process for producing paroxetine, which has an inhibitory action on 5-hydroxytryptamine (5-HT) and is useful as a therapeutic agent for various disease such as depression and Parkinson's disease.... Paroxetine is (3S,4R)-3-[5-(1,3-dioxaindanyl)oxymethyl]-4-(p-fluorophenyl)piperidine represented by the after-mentioned formula (4).... As processes for producing paroxetine, the process of Christensen et al. (U.S. Pat. No. 4,007,196) and the process of Barnes et al. (Japanese Examined Patent Publication JP-B-6-47587) have been known. The former comprises reacting a N-methylpiperidine derivative represented by the after-mentioned general formula (1) (wherein R.sup.1 is a methyl group) with phenyl chloroformate and hydrolyzing the resulting phenyl carbamate under alkaline conditions. The phenyl carbamate is different from compounds represented by the after-mentioned formula (3) only in that R.sup.2 is a phenyl group. This process has drawbacks attributed to the low degree of conversion into the phenyl carbamate, that extra time and labor are required to separate the starting materials from the product, and that the ultimate yield by the process is low. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Process for producing paroxetine salts substantially free from organic solvents Inventor(s): Saito, Erika; (Chiba-shi, JP), Wang, Shu-Zhong; (Yokohama-shi, JP), Shimokawa, Naoya; (Ischihara-shi, JP) Correspondence: OBLON, SPIVAK, MCCLELLAND, MAIER & NEUSTADT, P.C. 1940 DUKE STREET; ALEXANDRIA; VA; 22314; US Patent Application Number: 20030158416 Date filed: March 14, 2003 Abstract: A paroxetine salt free from an organic solvent is produced by substantially and safely removing the organic solvents from paroxetine hydrochloride.A process for producing a paroxetine salt, which comprises neutralizing paroxetine hydrochloride containing an organic solvent into paroxetine, then forming a salt of paroxetine with an acid other than hydrochloric acid, and crystallizing the salt from an organic solvent. Excerpt(s): The present invention relates to a process for producing paroxetine salts, which have an inhibitory action on 5-hydroxytryptamine (5-HT) and are useful as therapeutic agents for various diseases such as depression and Parkinson's disease.... Production of paroxetine salts, i.e., salts of (3S,4R)-3-[5-(1,3-dioxaindanyl)oxymethyl]-4(p-fluorophenyl)piperidine, as medicines involves reactions using organic solvents, and therefore, paroxetine salts are often produced with organic solvents in them. However, in view of the use of paroxetine salts as medicines, removal of organic solvents to a medicinally unproblematic level is necessary to provide paroxetine salts substantially free from organic solvents.... For removal of organic solvent from paroxetine salts, (1) vacuum drying of paroxetine hydrochloride containing an organic solvent with gradual changes in drying conditions and, optionally, irradiation with microwaves (WO00/8017) and (2) replacement of an organic solvent in paroxetine hydrochloride containing the organic solvent with water followed by dehydration (WO96/24595) have been proposed. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Process for the preparation of paroxetine substantially free of alkoxy impurities Inventor(s): Avrutov, Ilya; (Bat Hefer, IL), Niddam, Valerie; (Yehud, IL) Correspondence: KENYON & KENYON; ONE BROADWAY; NEW YORK; NY; 10004; US Patent Application Number: 20030055256 Date filed: June 13, 2002 Abstract: The present invention is directed to methods for preparing intermediates useful in the synthesis of paroxetine wherein the intermediates are substantially free of alkoxy impurities as well as to methods for preparing paroxetine and pharmaceutically acceptable salts thereof substantially free of alkoxy impurities. The alkoxy impurity is reacted with an ether cleaving agent to generate the corresponding phenol, which is separated, yielding the desired product substantially free of alkoxy impurities. Paroxetine intermediates such as PMA, paroxetine, and pharmaceutically acceptable salts thereof substantially free of alkoxy impurities also form part of the present invention. Excerpt(s): This application claims the benefit of provisional application Serial No. 60/297,881, filed Jun. 13, 2001, which is incorporated herein by reference.... Paroxetine is orally administered, inter alia, for the treatment of depression, social anxiety disorders, obsessive compulsive disorder, panic disorder, generalized anxiety disorder and posttraumatic stress disorder.... The '801 and the '517 patents and EP 223,334 A1 disclose catalyzing the reaction of the cinnamate and the amidomalonate with an alkali metal alkoxide, such as potassium tert-butoxide. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Process for the production of paroxetine Inventor(s): Picha, Frantisek; (Brno, CZ), Peters, Theodorus H. A. (Arnhem, NL), Lemmens, Jacobus M. (Mook, NL) Correspondence: SYNTHON PHARMACEUTICALS, LTD. PATENT DEPT. P.O. BOX 161; CATHARPIN; VA; 20143; US Patent Application Number: 20020151716 Date filed: February 15, 2002 Abstract: The synthesis of paroxetine can be made more convenient by using a solvent system comprising an aliphatic alcohol and a hydrocarbon co-solvent. The solvent system is used particularly in the hydrolysis of paroxetine phenylcarbamate and preferably uses butanol and toluene as the system. Excerpt(s): This application claims the benefit of priority under 35 U.S.C..sctn.119 from The Netherlands patent application serial number 1017421, filed Feb. 21, 2001, the entire contents of which are incorporated herein by reference.... The present invention relates to a process for preparing the pharmaceutically active compound paroxetine.... The compound has been used in therapy as the hydrochloride hemihydrate salt to treat e.g. depression, obsessive compulsive disorder and panic. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Stable pharmaceutical formulation of paroxetine hydrochloride anhydrous and a process for preparation thereof Inventor(s): Leibovici, Minutza; (Netanya, IL), Braunstein, Anne; (Modiin, IL), Cohen, Rakefet; (Zur Yigal, IL), Fox, Michael; (Tel Aviv, IL) Correspondence: KENYON & KENYON; ONE BROADWAY; NEW YORK; NY; 10004; US Patent Application Number: 20030144324 Date filed: December 27, 2002 Abstract: Provided are formulations of a stable commercial paroxetine tablet comprising paroxetine hydrochloride anhydrous, povidone, copovidone or HPMC as a binder, and an HCl free/non-hygroscopic filler, prepared by the wet granulation method. Excerpt(s): This application claims the benefit of provisional application Serial No. 60/344,120, filed Dec. 28, 2001 and provisional application Serial No. 60/366,351, filed Mar. 21, 2002, both of which are incorporated herein by reference.... The present invention relates to pharmaceutical formulations of paroxetine hydrochloride anhydrous and their preparation.... Paroxetine, disclosed in U.S. Pat. No. 4,007,196 (incorporated herein by reference), is an orally administered antidepressant for the treatment of depression, social anxiety disorders, obsessive compulsive disorder, panic disorder, generalized anxiety disorder and posttraumatic stress disorder. Other syndromes such as pre-menstrual syndrome (PMS) and male sexual dysfunction can also be treated with paroxetine. Paroxetine is marketed as Paxil.RTM., and in some countries as Seroxat.RTM. by GlaxoSmithKline. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with Paxil, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “Paxil” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on Paxil. You can also use this procedure to view pending patent applications concerning Paxil. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 6. BOOKS ON PAXIL Overview This chapter provides bibliographic book references relating to Paxil. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on Paxil include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “Paxil” at online booksellers’ Web sites, you may discover nonmedical books that use the generic term “Paxil” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “Paxil” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •

Prozac and the New Antidepressants: What You Need to Know About Prozac, Zoloft, Paxil, Luvox, Wellbutrin, Effexor, Serzone, and More by William S. Appleton (1997); ISBN: 0452274435; http://www.amazon.com/exec/obidos/ASIN/0452274435/icongroupinterna

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Prozac and the New Antidepressants: What You Need to Know About Prozac, Zoloft, Paxil, Luvox, Wellbutrin, Effexor, Serzone, Vestra, Celexa, St. John's Wort, and Others by William S. Appleton (2000); ISBN: 0452281644; http://www.amazon.com/exec/obidos/ASIN/0452281644/icongroupinterna

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Prozac Backlash: Overcoming the Dangers of Prozac, Zoloft, Paxil, and Other Antidepressants with Safe, Effective Alternatives by Joseph Glenmullen (Author) (2001); ISBN: 0743200624; http://www.amazon.com/exec/obidos/ASIN/0743200624/icongroupinterna

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Prozac: Panacea or Pandora? the Rest of the Story on the New Class of Ssri Antidepressants Prozac, Zoloft, Paxil, Lovan, Luvox & More. by Chase Shephard

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(Illustrator), et al; ISBN: 0916095592; http://www.amazon.com/exec/obidos/ASIN/0916095592/icongroupinterna •

The Anti-Depressant Fact Book: What Your Doctor Won't Tell You About Prozac, Zoloft, Paxil, Celexa, and Luvox by Peter R. Breggin, M.D. Peter R. Breggin (2001); ISBN: 073820451X; http://www.amazon.com/exec/obidos/ASIN/073820451X/icongroupinterna

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Zoloft, Paxil, Luvox and Prozac: All New Information to Help You Choose the Right Antidepressant by Donald L. Sullivan, Craig Williams (Introduction) (1999); ISBN: 0380795183; http://www.amazon.com/exec/obidos/ASIN/0380795183/icongroupinterna

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “Paxil” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:11 •

Selective serotonin re-uptake inhibitors: the clinical use of citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline Author: Feighner, John Preston,; Year: 1991; Chichester; New York: Wiley, c1991; ISBN: 0471928909 http://www.amazon.com/exec/obidos/ASIN/0471928909/icongroupinterna

Chapters on Paxil In order to find chapters that specifically relate to Paxil, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and Paxil using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and 11

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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language you prefer, and the format option “Book Chapter.” Type “Paxil” (or synonyms) into the “For these words:” box.

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CHAPTER 7. PERIODICALS AND NEWS ON PAXIL Overview In this chapter, we suggest a number of news sources and present various periodicals that cover Paxil.

News Services and Press Releases One of the simplest ways of tracking press releases on Paxil is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “Paxil” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to Paxil. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “Paxil” (or synonyms). The following was recently listed in this archive for Paxil: •

Early launch of generic Paxil knocks Glaxo Source: Reuters Medical News Date: September 09, 2003 http://www.reutershealth.com/archive/2003/09/09/professional/links/20030909inds 002.html

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US judge denies class action for Glaxo Paxil suit Source: Reuters Medical News Date: September 04, 2003

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Glaxo gets approval to market Paxil for PMS disorder Source: Reuters Medical News Date: September 02, 2003

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FDA warns against Paxil use in children Source: Reuters Medical News Date: June 19, 2003

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Children shouldn't use Paxil antidepressant: FDA Source: Reuters Health eLine Date: June 19, 2003

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Britain says paroxetine not safe for children Source: Reuters Medical News Date: June 10, 2003

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Paroxetine reduces number and severity of menopausal hot flashes Source: Reuters Medical News Date: May 02, 2003

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Paxil in pregnancy linked to complications for baby Source: Reuters Health eLine Date: November 11, 2002

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Glaxo gets OK for ads claiming Paxil not addictive Source: Reuters Health eLine Date: October 11, 2002

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Drug maker cuts 'non-habit forming' from Paxil ads Source: Reuters Health eLine Date: September 25, 2002

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Glaxo can continue running Paxil TV ads for now Source: Reuters Health eLine Date: August 23, 2002

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Paxil in pregnancy linked to baby's complications Source: Reuters Health eLine Date: May 06, 2002

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Paroxetine use during late pregnancy associated with neonatal complications Source: Reuters Medical News Date: May 06, 2002

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Paroxetine approved for posttraumatic stress disorder Source: Reuters Medical News Date: December 14, 2001

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Paroxetine improves major symptoms of posttraumatic stress disorder Source: Reuters Medical News Date: December 03, 2001

•

Lawsuit charges that Paxil is addictive Source: Reuters Health eLine Date: August 27, 2001

•

Paroxetine well tolerated and effective for major depression in adolescents Source: Reuters Medical News Date: July 30, 2001

•

Glaxo to contest $6.4 million Paxil jury award Source: Reuters Health eLine Date: June 08, 2001

•

Paroxetine treats depression, but not fatigue, during chemotherapy Source: Reuters Medical News Date: May 16, 2001

•

FDA approves Paxil for generalized anxiety disorder Source: Reuters Medical News Date: April 16, 2001

•

GlaxoSmithKline files Paxil patent complaint against Apotex Source: Reuters Industry Breifing Date: January 18, 2001

•

FDA approves Paxil for social phobia Source: Reuters Health eLine Date: May 12, 1999

•

FDA approves paroxetine for social anxiety disorder Source: Reuters Medical News Date: May 12, 1999

72 Paxil

•

SkyePharma, SmithKline get FDA approval for Paxil CR Source: Reuters Medical News Date: February 19, 1999

•

SmithKline gets UK approval of paroxetine for social anxiety disorder Source: Reuters Medical News Date: October 09, 1998

•

Scios to copromote SmithKline's Paxil Source: Reuters Medical News Date: September 14, 1998

•

SmithKline to file suit against generic paroxetine manufacturer Source: Reuters Medical News Date: May 22, 1998

•

Fluvoxamine, Paroxetine Equally Effective In Treatment Of Major Depression Source: Reuters Medical News Date: May 09, 1997

•

SmithKline Beecham's Paxil Cleared For Panic Disorder Source: Reuters Medical News Date: May 09, 1996

•

SmithKline Beecham's Paxil Approved In The U.K. For Panic Disorder Source: Reuters Medical News Date: November 22, 1995 The NIH

Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name.

Periodicals and News 73

Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “Paxil” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “Paxil” (or synonyms). If you know the name of a company that is relevant to Paxil, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “Paxil” (or synonyms).

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “Paxil” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on Paxil: •

Cause and Treatment of Pain in Chronic Intestinal Pseudo-Obstruction Source: ASAP Forum Journal. 2(1): 7-10. May 1995. Contact: Available from American Society of Adults with Pseudo-Obstruction (ASAP). 19 Carroll Road, Woburn, MA 01801. (617) 935-9776. Fax (617) 933-4151. Summary: This newsletter article addresses the cause and treatment of pain associated with chronic intestinal pseudo-obstruction (CIP). The author defines the current knowledge on the cause of pain, discusses the results obtained with the use of various medications and procedures, including surgical procedures, and provides thoughts on future developments for pain control. The author notes that although CIP produces

74 Paxil

numerous symptoms and problems, the subjective complaint that most patients have is that of abdominal pain. Specific drug agents covered include antacids; histamine blockers, such as Tagamet, Zantac, and Pepcid; Prilosec, an acid pump inhibitor; Carafate; nonsteroidal anti-inflammatory agents (NSAIDs), including ibuprofen, Motrin, or Orudis; antibiotics including Flagyl and Bactrim; antidepressants, including Librax, Ativan, and Paxil; pain inhibitors, including Darvon, Vicodin, and Lortab; Codeine; Percocet; Demerol; Morphine; Buprenex; Stadol; and Dilaudid.

Academic Periodicals covering Paxil Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to Paxil. In addition to these sources, you can search for articles covering Paxil that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

75

APPENDICES

77

APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute12: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

•

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

•

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

•

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

•

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

•

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

•

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

•

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

12

These publications are typically written by one or more of the various NIH Institutes.

78 Paxil

•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

Physician Resources 79

NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.13 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:14 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

13

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 14 See http://www.nlm.nih.gov/databases/databases.html.

80 Paxil

•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway15 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.16 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “Paxil” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 1784 2 43 7 2 1838

HSTAT17 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.18 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.19 Simply search by “Paxil” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

15

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

16

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 17 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 18 19

The HSTAT URL is http://hstat.nlm.nih.gov/.

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

Physician Resources 81

Coffee Break: Tutorials for Biologists20 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.21 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.22 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

20 Adapted 21

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 22 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

83

APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on Paxil can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to Paxil. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to Paxil. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “Paxil”:

84 Paxil

•

Other Guides About Your Medicines http://www.nlm.nih.gov/medlineplus/aboutyourmedicines.html Obsessive-Compulsive Disorder http://www.nlm.nih.gov/medlineplus/obsessivecompulsivedisorder.html Panic Disorder http://www.nlm.nih.gov/medlineplus/panicdisorder.html Post-Traumatic Stress Disorder http://www.nlm.nih.gov/medlineplus/posttraumaticstressdisorder.html

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. Healthfinder™ Healthfinder™ is sponsored by the U.S. Department of Health and Human Services and offers links to hundreds of other sites that contain healthcare information. This Web site is located at http://www.healthfinder.gov. Again, keyword searches can be used to find guidelines. The following was recently found in this database: •

Paxil (Paroxetine) Summary: Paroxetine (pa-ROX-uh-teen), called by brand name Source: National Library of Medicine, National Institutes of Health http://www.healthfinder.gov/scripts/recordpass.asp?RecordType=0&RecordID=6865 The NIH Search Utility

The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to Paxil. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html.

Patient Resources 85

Additional Web Sources

A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •


•

Family Village: http://www.familyvillage.wisc.edu/specific.htm

•

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

•

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

•

WebMDHealth: http://my.webmd.com/health_topics

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to Paxil. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with Paxil. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about Paxil. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “Paxil” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received

86 Paxil

your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “Paxil”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “Paxil” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “Paxil” (or a synonym) into the search box, and click “Submit Query.”

87

APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.23

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

23

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

88 Paxil

libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)24: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

24

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

Finding Medical Libraries 89

•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

•

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

•

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

•

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

Finding Medical Libraries 91

•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

•

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

93

ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

•

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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PAXIL DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Acetone: A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acylation: The addition of an organic acid radical into a molecule. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]

Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean

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intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Agoraphobia: Obsessive, persistent, intense fear of open places. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkylation: The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amitriptyline: Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the re-uptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antaganize cholinergic and alpha-1 adrenergic responses to bioactive amines. [NIH] Ammonium Chloride: An acidifying agent that is used as an expectorant and a diuretic. [NIH]

Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [NIH] Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral

Dictionary 97

ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]

Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anhydrous: Deprived or destitute of water. [EU] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antibiotics: Substances produced by microorganisms that can inhibit or suppress the growth of other microorganisms. [NIH] Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulants: Agents that prevent blood clotting. Naturally occurring agents in the blood are included only when they are used as drugs. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]

Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the

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antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Antiviral: Destroying viruses or suppressing their replication. [EU] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Aqueous: Having to do with water. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant. [NIH] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord.

Dictionary 99

Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Autonomic: Self-controlling; functionally independent. [EU] Autoreceptors: Transmitter receptors on or near presynaptic terminals (or varicosities) which are sensitive to the transmitter(s) released by the terminal itself. Receptors for the hormones released by hormone-releasing cells are also included. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Behavior Therapy: The application of modern theories of learning and conditioning in the treatment of behavior disorders. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological response modifier: BRM. A substance that stimulates the body's response to infection and disease. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and

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clearance. [NIH] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Blood Cell Count: A count of the number of leukocytes and erythrocytes per unit volume in a sample of venous blood. A complete blood count (CBC) also includes measurement of the hemoglobin, hematocrit, and erythrocyte indices. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood Volume: Volume of circulating blood. It is the sum of the plasma volume and erythrocyte volume. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradycardia: Excessive slowness in the action of the heart, usually with a heart rate below 60 beats per minute. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bulimia: Episodic binge eating. The episodes may be associated with the fear of not being able to stop eating, depressed mood, or self-deprecating thoughts (binge-eating disorder) and may frequently be terminated by self-induced vomiting (bulimia nervosa). [NIH] Bupropion: A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal

Dictionary 101

functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogenic: Producing carcinoma. [EU] Carcinogens: Substances that increase the risk of neoplasms in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiac arrest: A sudden stop of heart function. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Carotid Sinus: The dilated portion of the common carotid artery at its bifurcation into external and internal carotids. It contains baroreceptors which, when stimulated, cause slowing of the heart, vasodilatation, and a fall in blood pressure. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Chaos: Complex behavior that seems random but actually has some hidden order. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH]

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Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chlordiazepoxide: An anxiolytic benzodiazepine derivative with anticonvulsant, sedative, and amnesic properties. It has also been used in the symptomatic treatment of alcohol withdrawl. [NIH] Chlorpromazine: The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Citalopram: A selective neuronal serotonin reuptake inhibitor and a clinically effective antidepressant with tolerable side effects. The drug is also effective in reducing ethanol uptake in alcoholics and is used in depressed patients who also suffer from tardive dyskinesia (TD) in preference to tricyclic antidepressants, which aggravate this condition. [NIH]

Citric Acid: A key intermediate in metabolism. It is an acid compound found in citrus fruits. The salts of citric acid (citrates) can be used as anticoagulants due to their calcium chelating ability. [NIH] Citrus: Any tree or shrub of the Rue family or the fruit of these plants. [NIH] Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clonazepam: An anticonvulsant used for several types of seizures, including myotonic or atonic seizures, photosensitive epilepsy, and absence seizures, although tolerance may develop. It is seldom effective in generalized tonic-clonic or partial seizures. The mechanism of action appears to involve the enhancement of gaba receptor responses. [NIH] Clonic: Pertaining to or of the nature of clonus. [EU] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coal: A natural fuel formed by partial decomposition of vegetable matter under certain environmental conditions. [NIH] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is

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thought to involve inhibition of dopamine uptake. [NIH] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colloidal: Of the nature of a colloid. [EU] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Compulsions: In psychology, an irresistible urge, sometimes amounting to obsession to

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perform a particular act which usually is carried out against the performer's will or better judgment. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups

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and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, ... New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Decompression: Decompression external to the body, most often the slow lessening of external pressure on the whole body (especially in caisson workers, deep sea divers, and persons who ascend to great heights) to prevent decompression sickness. It includes also sudden accidental decompression, but not surgical (local) decompression or decompression applied through body openings. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydration: The condition that results from excessive loss of body water. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Demethylation: Process that releases substantial amounts of carbon dioxide in the liver. [NIH]

Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Depersonalization: Alteration in the perception of the self so that the usual sense of one's own reality is lost, manifested in a sense of unreality or self-estrangement, in changes of body image, or in a feeling that one does not control his own actions and speech; seen in depersonalization disorder, schizophrenic disorders, and schizotypal personality disorder. Some do not draw a distinction between depersonalization and derealization, using depersonalization to include both. [EU] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Derealization: Is characterized by the loss of the sense of reality concerning one's surroundings. [NIH] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diathermy: The induction of local hyperthermia by either short radio waves or high-

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frequency sound waves. [NIH] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dilatation: The act of dilating. [NIH] Dilution: A diluted or attenuated medicine; in homeopathy, the diffusion of a given quantity of a medicinal agent in ten or one hundred times the same quantity of water. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dyspnea: Difficult or labored breathing. [NIH]

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Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Ejaculation: The release of semen through the penis during orgasm. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electroencephalography: Recording of electric currents developed in the brain by means of electrodes applied to the scalp, to the surface of the brain, or placed within the substance of the brain. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Enuresis: Involuntary discharge of urine after the age at which urinary control should have been achieved; often used alone with specific reference to involuntary discharge of urine occurring during sleep at night (bed-wetting, nocturnal enuresis). [EU] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH] Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Ergot: Cataract due to ergot poisoning caused by eating of rye cereals contaminated by a fungus. [NIH] Erythrocyte Indices: Quantification of size and cell hemoglobin content or concentration of the erythrocyte, usually derived from erythrocyte count, blood hemoglobin concentration, and hematocrit. Includes the mean cell volume (MCV), mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC). Use also for cell diameter and thickness. [NIH] Erythrocytes:

Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks

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containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Excipients: Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form; a binder, matrix, base or diluent in pills, tablets, creams, salves, etc. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expander: Any of several colloidal substances of high molecular weight... used as a blood or plasma substitute in transfusion for increasing the volume of the circulating blood... called also extender. [NIH] Expectorant: 1. Promoting the ejection, by spitting, of mucus or other fluids from the lungs and trachea. 2. An agent that promotes the ejection of mucus or exudate from the lungs, bronchi, and trachea; sometimes extended to all remedies that quiet cough (antitussives). [EU]

Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Filler: An inactive substance used to make a product bigger or easier to handle. For example, fillers are often used to make pills or capsules because the amount of active drug is too small to be handled conveniently. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral

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cortex which involves the entire thickness of the brain wall. [EU] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatus: Gas passed through the rectum. [NIH] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Fluvoxamine: A selective serotonin reuptake inhibitor. It is effective in the treatment of depression, obsessive-compulsive disorders, anxiety, panic disorders, and alcohol amnestic disorders. [NIH] Food Technology: The application of knowledge to the food industry. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] GABA: The most common inhibitory neurotransmitter in the central nervous system. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gasoline: Volative flammable fuel (liquid hydrocarbons) derived from crude petroleum by processes such as distillation reforming, polymerization, etc. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Glucocorticoids:

A group of corticosteroids that affect carbohydrate metabolism

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(gluconeogenesis, liver glycogen deposition, elevation of blood sugar), inhibit corticotropin secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Granule: A small pill made from sucrose. [EU] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Habituation: Decline in response of an organism to environmental or other stimuli with repeated or maintained exposure. [NIH] Haematoma: A localized collection of blood, usually clotted, in an organ, space, or tissue, due to a break in the wall of a blood vessel. [EU] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Hallucinogen: A hallucination-producing drug, a category of drugs producing this effect. The user of a hallucinogenic drug is almost invariably aware that what he is seeing are hallucinations.. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Hematocrit: Measurement of the volume of packed red cells in a blood specimen by centrifugation. The procedure is performed using a tube with graduated markings or with automated blood cell counters. It is used as an indicator of erythrocyte status in disease. For example, anemia shows a low hematocrit, polycythemia, high values. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH]

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Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Hepatotoxicity: How much damage a medicine or other substance does to the liver. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH] Hiccup: A spasm of the diaphragm that causes a sudden inhalation followed by rapid closure of the glottis which produces a sound. [NIH] Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hydrochloric Acid: A strong corrosive acid that is commonly used as a laboratory reagent. It is formed by dissolving hydrogen chloride in water. Gastric acid is the hydrochloric acid component of gastric juice. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogenation: Specific method of reduction in which hydrogen is added to a substance by the direct use of gaseous hydrogen. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic

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acid can result in impaired hydroxyproline formation. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypotension: Abnormally low blood pressure. [NIH] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the therapy of rheumatism and arthritis. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Immune response: (antigens). [NIH]

The activity of the immune system against foreign substances

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunology: The study of the body's immune system. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU]

Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and -

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gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH] Interferon Alfa-2b: A recombinant alfa interferon consisting of 165 amino acid residues with arginine in position 23 and histidine in position 34. It is used extensively as an antiviral and antineoplastic agent. [NIH] Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestinal: Having to do with the intestines. [NIH] Intestinal Pseudo-Obstruction: mechanical. [NIH]

Obstruction of the intestines that is functional, not

Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Involuntary: Reaction occurring without intention or volition. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Isopropyl: A gene mutation inducer. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Ketoacidosis: Acidosis accompanied by the accumulation of ketone bodies (ketosis) in the body tissues and fluids, as in diabetic acidosis. [EU] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] Kinetic: Pertaining to or producing motion. [EU]

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Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Library Services: circulation. [NIH]

Services offered to the library user. They include reference and

Ligands: A RNA simulation method developed by the MIT. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]

Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Lower Body Negative Pressure: External decompression applied to the lower body. It is used to study orthostatic intolerance and the effects of gravitation and acceleration, to produce simulated hemorrhage in physiologic research, to assess cardiovascular function, and to reduce abdominal stress during childbirth. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lysergic acid: A compound close in chemical structure to LSD-25 but without hallucinogenic effects; one of the direct chemical predecessors of LSD-25. Sometimes LSD-25 is erroneously called by this name. [NIH] Lysergic Acid Diethylamide: Semisynthetic derivative of ergot (Claviceps purpurea). It has complex effects on serotonergic systems including antagonism at some peripheral serotonin receptors, both agonist and antagonist actions at central nervous system serotonin receptors, and possibly effects on serotonin turnover. It is a potent hallucinogen, but the mechanisms of that effect are not well understood. [NIH] Maintenance therapy: Treatment that is given to help a primary (original) treatment keep working. Maintenance therapy is often given to help keep cancer in remission. [NIH] Manic: Affected with mania. [EU]

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Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Methamphetamine: A central nervous system stimulant and sympathomimetic with actions and uses similar to dextroamphetamine. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed. [NIH] Methanol: A colorless, flammable liquid used in the manufacture of formaldehyde and acetic acid, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness. [NIH] Methylene Chloride: A chlorinated hydrocarbon that has been used as an inhalation anesthetic and acts as a narcotic in high concentrations. Its primary use is as a solvent in manufacturing and food technology. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [NIH] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living

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organisms, they are sometimes classified as microorganisms. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Microwaves: That portion of the electromagnetic spectrum lying between UHF (ultrahigh frequency) radio waves and heat (infrared) waves. Microwaves are used to generate heat, especially in some types of diathermy. They may cause heat damage to tissues. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Moclobemide: A reversible inhibitor of monoamine oxidase type A (RIMA) that has antidepressive properties. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Mood Disorders: Those disorders that have a disturbance in mood as their predominant feature. [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU]

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Muscle Spindles: Mechanoreceptors found between skeletal muscle fibers. Muscle spindles are arranged in parallel with muscle fibers and respond to the passive stretch of the muscle, but cease to discharge if the muscle contracts isotonically, thus signaling muscle length. The muscle spindles are the receptors responsible for the stretch or myotactic reflex. [NIH] Mutism: Inability or refusal to speak. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU]

Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neurosis: Functional derangement due to disorders of the nervous system which does not affect the psychic personality of the patient. [NIH] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal,

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and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nortriptyline: A metabolite of amitryptyline that is also used as an antidepressive agent. Nortriptyline is used in major depression, dysthymia, and atypical depressions. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Obsessive-Compulsive Disorder: An anxiety disorder characterized by recurrent, persistent obsessions or compulsions. Obsessions are the intrusive ideas, thoughts, or images that are experienced as senseless or repugnant. Compulsions are repetitive and seemingly purposeful behavior which the individual generally recognizes as senseless and from which the individual does not derive pleasure although it may provide a release from tension. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Orgasm: The crisis of sexual excitement in either humans or animals. [NIH] Orthostatic: Pertaining to or caused by standing erect. [EU] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Oxidants: Oxidizing agents or electron-accepting molecules in chemical reactions in which electrons are transferred from one molecule to another (oxidation-reduction). In vivo, it appears that phagocyte-generated oxidants function as tumor promoters or cocarcinogens rather than as complete carcinogens perhaps because of the high levels of endogenous antioxidant defenses. It is also thought that oxidative damage in joints may trigger the autoimmune response that characterizes the persistence of the rheumatoid disease process. [NIH]

Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological

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oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Paclitaxel: Antineoplastic agent isolated from the bark of the Pacific yew tree, Taxus brevifolia. Paclitaxel stabilizes microtubules in their polymerized form and thus mimics the action of the proto-oncogene proteins c-mos. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [NIH] Paresthesias: Abnormal touch sensations, such as burning or prickling, that occur without an outside stimulus. [NIH] Paroxetine: A serotonin uptake inhibitor that is effective in the treatment of depression. [NIH]

Paroxetine hydrochloride: An antidepressant drug. [NIH] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH]

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Peripheral blood: Blood circulating throughout the body. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Phagocyte: An immune system cell that can surround and kill microorganisms and remove dead cells. Phagocytes include macrophages. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylalanine: An aromatic amino acid that is essential in the animal diet. It is a precursor of melanin, dopamine, noradrenalin, and thyroxine. [NIH] Phenytoin: An anticonvulsant that is used in a wide variety of seizures. It is also an antiarrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs. [NIH] Phobia: A persistent, irrational, intense fear of a specific object, activity, or situation (the phobic stimulus), fear that is recognized as being excessive or unreasonable by the individual himself. When a phobia is a significant source of distress or interferes with social functioning, it is considered a mental disorder; phobic disorder (or neurosis). In DSM III phobic disorders are subclassified as agoraphobia, social phobias, and simple phobias. Used as a word termination denoting irrational fear of or aversion to the subject indicated by the stem to which it is affixed. [EU] Phobic Disorders: Anxiety disorders in which the essential feature is persistent and irrational fear of a specific object, activity, or situation that the individual feels compelled to avoid. The individual recognizes the fear as excessive or unreasonable. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of

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organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Positron emission tomography scan: PET scan. A computerized image of the metabolic activity of body tissues used to determine the presence of disease. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Post-traumatic stress disorder: A psychological disorder that develops in some individuals after a major traumatic experience such as war, rape, domestic violence, or accident. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potassium hydroxide: A toxic and highly corrosive chemical used to make soap, in bleaching, and as a paint remover. It is used in small amounts as a food additive and in the preparatrion of some drugs. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Povidone: A polyvinyl polymer of variable molecular weight; used as suspending and dispersing agent and vehicle for pharmaceuticals; also used as blood volume expander. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precipitation: The act or process of precipitating. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prefrontal Cortex: The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the mediodorsal nucleus of the thalamus. The prefrontal cortex receives afferent fibers from numerous structures of the diencephalon, mesencephalon, and limbic system as well as cortical afferents of visual, auditory, and somatic origin. [NIH] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU]

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Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity. [NIH] Proto-Oncogene Proteins c-mos: Cellular proteins encoded by the c-mos genes. They function in the cell cycle to maintain maturation promoting factor in the active state and have protein-serine/threonine kinase activity. Oncogenic transformation can take place when c-mos proteins are expressed at the wrong time. [NIH] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH]

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Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychophysiology: The study of the physiological basis of human and animal behavior. [NIH]

Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Purifying: Respiratory equipment whose function is to remove contaminants from otherwise wholesome air. [NIH] Quinidine: An optical isomer of quinine, extracted from the bark of the Cinchona tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular action potential, and decreases automaticity. Quinidine also blocks muscarinic and alphaadrenergic neurotransmission. [NIH] Quinine: An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radio Waves: That portion of the electromagnetic spectrum beyond the microwaves, with wavelengths as high as 30 KM. They are used in communications, including television. Short Wave or HF (high frequency), UHF (ultrahigh frequency) and VHF (very high frequency) waves are used in citizen's band communication. [NIH] Radioactive: Giving off radiation. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH]

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Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Rape: Unlawful sexual intercourse without consent of the victim. [NIH] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Recombinant: A cell or an individual with a new combination of genes not found together in either parent; usually applied to linked genes. [EU] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Resolving: The ability of the eye or of a lens to make small objects that are close together, separately visible; thus revealing the structure of an object. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risperidone: A selective blocker of dopamine D2 and serotonin-5-HT-2 receptors that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of schizophrenia. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate

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affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Sertraline: A selective serotonin uptake inhibitor that is used in the treatment of depression. [NIH]

Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Sleep Deprivation: The state of being deprived of sleep under experimental conditions, due to life events, or from a wide variety of pathophysiologic causes such as medication effect, chronic illness, psychiatric illness, or sleep disorder. [NIH] Smoking Cessation: Discontinuation of the habit of smoking, the inhaling and exhaling of tobacco smoke. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels.

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[NIH]

Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somnambulism: A parasomnia characterized by a partial arousal that occurs during stage IV of non-REM sleep. Affected individuals exhibit semipurposeful behaviors such as ambulation and are difficult to fully awaken. Children are primarily affected, with a peak age range of 4-6 years. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Stabilization: The creation of a stable state. [EU] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain.

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[NIH]

Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suspensions: Colloids with liquid continuous phase and solid dispersed phase; the term is used loosely also for solid-in-gas (aerosol) and other colloidal systems; water-insoluble drugs may be given as suspensions. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatic treatment: Therapy that eases symptoms without addressing the cause of disease. [NIH] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]

Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH]

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Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]

Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also

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called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vasodilatation: A state of increased calibre of the blood vessels. [EU] Vasodilator: An agent that widens blood vessels. [NIH] VE: The total volume of gas either inspired or expired in one minute. [NIH] Veins: The vessels carrying blood toward the heart. [NIH] Venlafaxine: An antidepressant drug that is being evaluated for the treatment of hot flashes in women who have breast cancer. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] War: Hostile conflict between organized groups of people. [NIH] Weight Gain: Increase in body weight over existing weight. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH]

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X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH]

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INDEX A Abdominal, 74, 95, 114, 119 Abdominal Pain, 74, 95 Acetone, 61, 95, 113 Acetylcholine, 95, 102, 117 Acylation, 56, 95 Adaptation, 95, 102 Adrenal Cortex, 95, 104 Adrenal Medulla, 95, 107, 118 Adrenergic, 95, 96, 98, 106, 107, 123, 127 Adverse Effect, 39, 95, 120, 125 Aerosol, 95, 127 Afferent, 95, 121 Affinity, 25, 44, 95, 96, 99, 126 Agonist, 96, 106, 114 Agoraphobia, 39, 40, 96, 119, 120 Algorithms, 96, 99 Alkaline, 61, 62, 96, 100 Alkaloid, 96, 102, 123 Alkylation, 51, 96 Allergen, 96, 125 Alpha-1, 96 Alternative medicine, 73, 96 Amine, 96, 111 Amino acid, 25, 96, 97, 98, 110, 111, 113, 119, 120, 122, 125, 128 Amitriptyline, 9, 10, 25, 96 Ammonium Chloride, 61, 96 Amnestic, 96, 109 Amphetamines, 96, 102 Amygdala, 33, 37, 96, 114 Anaesthesia, 18, 32, 97 Analgesic, 97, 112, 123 Analogous, 57, 97, 128 Anatomical, 97, 102, 112, 115 Androgens, 95, 97, 104 Anesthesia, 17, 97 Anhydrous, 45, 48, 52, 53, 60, 64, 97 Anorexia, 52, 96, 97 Antagonism, 97, 114 Antibiotics, 74, 97 Antibodies, 97, 110, 114 Antibody, 95, 97, 103, 110, 111, 112, 113, 115, 116, 123, 125, 126, 130 Anticholinergic, 96, 97 Anticoagulants, 97, 102 Anticonvulsant, 97, 101, 102, 120 Antiemetic, 97, 98, 102

Antigen, 95, 97, 103, 111, 112, 115, 125 Anti-inflammatory, 74, 98, 104, 110, 112 Anti-Inflammatory Agents, 74, 98, 104 Antineoplastic, 98, 104, 113, 119 Antioxidant, 98, 118 Antipsychotic, 98, 102, 124 Antiseptic, 95, 98 Antiviral, 98, 113 Anxiety, 6, 8, 9, 11, 12, 17, 19, 21, 30, 31, 34, 37, 38, 44, 61, 63, 64, 71, 72, 98, 109, 118, 119, 120 Anxiety Disorders, 21, 61, 63, 64, 98, 119 Anxiolytic, 98, 102 Aqueous, 44, 45, 59, 98, 99, 114 Arginine, 98, 113 Arrhythmia, 98, 129 Arterial, 98, 110, 112, 122, 127 Arteries, 98, 100, 104, 115 Arterioles, 98, 100 Artery, 98, 100, 101, 104, 129 Ascorbic Acid, 61, 98, 112 Astrocytes, 98, 115, 116 Atypical, 99, 118, 124 Auditory, 99, 121 Autonomic, 95, 98, 99, 118, 120 Autoreceptors, 25, 99 B Bacteria, 97, 99, 115, 126 Bactericidal, 99, 108 Base, 45, 50, 56, 57, 59, 61, 99, 108, 113, 127 Behavior Therapy, 39, 99 Benign, 44, 99, 123 Benzene, 59, 60, 99 Bioavailability, 50, 99 Biochemical, 21, 99, 125 Biological response modifier, 99, 112 Biotechnology, 6, 66, 73, 79, 99 Biotransformation, 99 Bipolar Disorder, 24, 26, 100 Blood Cell Count, 39, 100, 110 Blood Coagulation, 100, 101 Blood Platelets, 100, 125 Blood pressure, 100, 101, 110, 112, 126 Blood vessel, 39, 100, 101, 102, 110, 119, 125, 126, 127, 129 Blood Volume, 100, 121 Bone Marrow, 99, 100, 112 Bowel, 11, 21, 100, 106, 113

132 Paxil

Bowel Movement, 100, 106 Brachytherapy, 100, 113, 123, 130 Bradycardia, 19, 100 Branch, 91, 100, 119, 126, 127 Breakdown, 100, 106, 109 Bronchial, 100, 111 Bulimia, 52, 100 Bupropion, 39, 100 C Calcium, 40, 100, 101, 102, 103, 129 Calcium channel blocker, 101, 129 Capsules, 53, 58, 59, 101, 106, 108 Carbamazepine, 25, 101 Carbohydrate, 101, 104, 109 Carbon Dioxide, 101, 105, 109, 129 Carcinogenic, 99, 101, 126 Carcinogens, 101, 118 Cardiac, 10, 32, 101, 107, 108, 117, 123, 126 Cardiac arrest, 32, 101 Cardiovascular, 101, 114, 125 Carotid Sinus, 20, 33, 101 Case report, 44, 101 Cell, 96, 99, 101, 103, 107, 108, 112, 113, 115, 116, 117, 120, 121, 122, 124, 128, 129 Central Nervous System, 49, 95, 96, 99, 101, 102, 105, 109, 110, 114, 115, 125 Cerebral, 25, 30, 31, 37, 101, 107, 108, 109, 123, 127 Cerebral Cortex, 25, 101, 109 Cerebrospinal, 8, 101 Cerebrospinal fluid, 8, 101 Cerebrum, 101, 127 Chaos, 14, 101 Chemotherapy, 71, 101 Chin, 102, 115 Chlordiazepoxide, 44, 102 Chlorpromazine, 34, 102 Cholinergic, 96, 98, 102 Chronic, 11, 16, 26, 30, 73, 102, 112, 122, 125 Citalopram, 9, 24, 32, 39, 66, 102 Citric Acid, 44, 102 Citrus, 98, 102 Clinical Medicine, 102, 121 Clinical trial, 18, 37, 41, 79, 102, 104, 106, 124 Clonazepam, 38, 102 Clonic, 102 Cloning, 99, 102 Coal, 99, 102 Coca, 102 Cocaine, 102

Coenzyme, 98, 103 Cofactor, 103, 122 Collagen, 96, 103 Colloidal, 103, 108, 127 Complement, 103, 125 Complementary and alternative medicine, 29, 36, 103 Complementary medicine, 29, 103 Complete remission, 103, 124 Compulsions, 103, 118 Computational Biology, 79, 104 Conjugated, 104 Connective Tissue, 98, 100, 103, 104, 109, 110, 124 Consciousness, 97, 104, 105, 106, 122 Contraindications, ii, 104 Controlled study, 7, 8, 17, 19, 104 Coronary, 104, 115 Coronary Thrombosis, 104, 115 Cortex, 32, 104, 107, 121 Cortical, 24, 25, 104, 121, 125 Corticosteroid, 13, 104 Cortisol, 9, 104 Crystallization, 48, 104 Cytochrome, 10, 22, 104 D Decarboxylation, 105, 111 Decompression, 105, 114 Degenerative, 105, 111 Dehydration, 62, 105 Dementia, 13, 52, 98, 105 Demethylation, 59, 105 Dentate Gyrus, 105, 111 Depersonalization, 105, 119, 124 Depressive Disorder, 30, 105, 114 Derealization, 105, 119 Deuterium, 105, 111 Dextroamphetamine, 105, 115 Diagnostic procedure, 43, 73, 105 Diastolic, 105, 112 Diathermy, 105, 116 Diencephalon, 106, 121, 127 Digestion, 100, 106, 113, 114, 126 Digestive system, 41, 106 Dilatation, 106, 122 Dilution, 13, 106 Direct, iii, 53, 102, 106, 111, 114, 123, 124 Disinfectant, 106, 108 Dissociation, 95, 106 Dizziness, 106, 119 Dopamine, 31, 98, 100, 102, 103, 105, 106, 116, 117, 120, 124

Index 133

Dosage Forms, 53, 58, 60, 61, 106 Double-blind, 7, 8, 11, 14, 17, 18, 20, 25, 106 Dyskinesia, 98, 102, 106 Dysphoric, 105, 106 Dyspnea, 106, 119 E Efficacy, 7, 8, 12, 21, 40, 55, 107, 128 Ejaculation, 8, 19, 44, 107, 125 Elective, 20, 66, 107 Electroencephalography, 19, 107 Electrolyte, 104, 107, 116, 121, 126 Endocrine System, 107, 117 Endogenous, 106, 107, 118 Endorphins, 107, 117 Enkephalins, 107, 117 Entorhinal Cortex, 107, 111 Enuresis, 17, 107 Environmental Health, 78, 80, 107 Enzymatic, 56, 96, 101, 103, 107, 111 Enzyme, 46, 56, 103, 107, 116, 129 Epinephrine, 95, 106, 107, 117, 118, 128 Ergot, 107, 114 Erythrocyte Indices, 100, 107 Erythrocytes, 100, 107, 125 Esophagus, 106, 108, 126 Ethanol, 59, 102, 108 Ether, 59, 63, 108 Excipients, 53, 60, 108 Excitability, 108, 123 Excitation, 96, 108, 117 Exogenous, 99, 107, 108 Expander, 108, 121 Expectorant, 96, 108 Extensor, 108, 122 External-beam radiation, 108, 113, 123, 130 Extracellular, 99, 104, 108, 115, 126 Extracellular Space, 108, 115 F Family Planning, 79, 108 Fat, 100, 104, 108, 110, 113, 124 Fatigue, 25, 71, 108 Fatty acids, 33, 108 Filler, 64, 108 Filtration, 52, 108 Fissure, 105, 108, 121 Fixation, 109, 125 Flatus, 109 Fluoxetine, 9, 10, 15, 24, 25, 28, 39, 44, 66, 109 Fluvoxamine, 24, 36, 39, 66, 72, 109

Food Technology, 109, 115 Frontal Lobe, 109, 121 Fungi, 109, 115 G GABA, 102, 109 Gallbladder, 95, 106, 109 Ganglia, 95, 98, 109, 114, 117, 120 Gas, 13, 101, 109, 111, 118, 127, 129 Gasoline, 99, 109 Gastric, 13, 106, 109, 111 Gastrointestinal, 107, 108, 109, 125 Gastrointestinal tract, 108, 109, 125 Gene, 66, 99, 109, 113 Genotype, 10, 109 Glucocorticoids, 95, 104, 109 Glucose, 30, 31, 98, 110 Glutamic Acid, 110, 117 Glycine, 96, 110, 117 Governing Board, 110, 121 Granule, 59, 105, 110 Growth, 97, 98, 110, 112, 115, 120, 122, 127, 128 H Habituation, 37, 110 Haematoma, 26, 110 Half-Life, 22, 110 Hallucinogen, 110, 114 Haptens, 95, 110 Hematocrit, 100, 107, 110 Heme, 104, 110 Hemoglobin, 100, 107, 108, 110 Hemorrhage, 110, 114, 126 Hemostasis, 111, 125 Hepatitis, 16, 111 Hepatocytes, 111 Hepatotoxicity, 15, 111 Heredity, 109, 111 Heterogeneity, 44, 95, 111 Hiccup, 102, 111 Hippocampus, 37, 105, 111, 114, 127 Histamine, 74, 98, 111 Histidine, 111, 113 Homologous, 111, 125, 127 Hormonal, 104, 111 Hormone, 99, 104, 107, 111, 127 Hydrochloric Acid, 62, 111 Hydrogen, 46, 56, 60, 96, 99, 101, 105, 111, 116, 117, 119, 122 Hydrogenation, 51, 111 Hydrolysis, 46, 63, 99, 111 Hydrophobic, 53, 111 Hydroxyproline, 96, 103, 111

134 Paxil

Hypersensitivity, 96, 112, 125 Hypertension, 40, 112 Hypotension, 6, 98, 112 I Ibuprofen, 74, 112 Id, 27, 35, 85, 90, 92, 112 Immune response, 97, 104, 110, 112, 125, 129 Immune system, 112, 114, 117, 120, 129 Immunization, 112, 125 Immunology, 95, 112 Impairment, 18, 106, 112, 115 Implant radiation, 112, 113, 123, 130 In vitro, 9, 112 In vivo, 25, 33, 112, 115, 118 Indicative, 65, 112, 119 Infarction, 104, 112, 115 Infection, 99, 112, 114, 129 Inflammation, 98, 111, 112, 121, 124 Inhalation, 95, 111, 112, 115, 121 Interferon, 16, 33, 112, 113 Interferon Alfa-2b, 33, 113 Interferon-alpha, 16, 112, 113 Internal radiation, 113, 123, 130 Interstitial, 100, 108, 113, 130 Intestinal, 73, 113 Intestinal Pseudo-Obstruction, 73, 113 Intestine, 100, 111, 113, 114 Intoxication, 22, 113, 129 Intracellular, 31, 33, 112, 113, 121, 124 Intrinsic, 96, 113 Involuntary, 107, 113, 117 Ions, 99, 106, 107, 111, 113 Irradiation, 62, 113, 130 Isopropyl, 46, 113 K Kb, 78, 113 Ketoacidosis, 95, 113 Ketone Bodies, 95, 113 Kinetic, 113 L Large Intestine, 106, 113, 114, 124 Latent, 34, 114 Lens, 114, 124 Leukocytes, 100, 113, 114 Library Services, 90, 114 Ligands, 51, 114 Limbic, 97, 114, 121 Limbic System, 97, 114, 121 Lithium, 25, 26, 98, 114 Liver, 95, 105, 106, 109, 110, 111, 114, 116 Localized, 32, 109, 110, 112, 114, 116, 120

Lower Body Negative Pressure, 20, 33, 114 Lymphocyte, 10, 98, 114, 115 Lysergic acid, 24, 114 Lysergic Acid Diethylamide, 24, 114 M Maintenance therapy, 40, 114 Manic, 98, 100, 114 Mediator, 115, 125 MEDLINE, 79, 115 Melanin, 115, 120, 128 Membrane, 99, 103, 108, 115, 120, 123 Memory, 10, 37, 97, 105, 115 Meninges, 101, 115 Mental, v, 19, 37, 38, 39, 41, 78, 80, 101, 102, 105, 106, 108, 115, 120, 122, 123, 124 Mental Disorders, 41, 115, 122 Metabolite, 99, 115, 118 Methamphetamine, 9, 115 Methanol, 61, 115 Methylene Chloride, 60, 115 MI, 93, 115 Microbe, 115, 128 Microdialysis, 33, 115 Microglia, 99, 115, 116 Microorganism, 46, 103, 115, 129 Microtubules, 116, 119 Microwaves, 62, 116, 123 Migration, 60, 116 Mineralocorticoids, 95, 104, 116 Mobilization, 33, 116 Moclobemide, 21, 116 Modification, 48, 96, 116 Molecular, 79, 81, 99, 104, 105, 108, 116, 121, 124, 128 Molecule, 51, 95, 97, 99, 103, 106, 108, 111, 116, 118, 119, 123, 124 Monoamine, 26, 105, 116 Monoamine Oxidase, 105, 116 Monoclonal, 113, 116, 123, 130 Mood Disorders, 116 Motility, 116, 125 Motion Sickness, 116, 117 Mucins, 116, 124 Muscle relaxant, 116, 120 Muscle Spindles, 117, 120 Mutism, 6, 19, 117 Myocardium, 115, 117 N Naive, 29, 117 Narcotic, 115, 117 Nausea, 34, 97, 98, 106, 117, 119

Index 135

NCI, 1, 41, 77, 117 Need, 45, 50, 60, 65, 66, 73, 86, 117, 128 Neonatal, 71, 117 Nerve, 95, 96, 97, 102, 115, 116, 117, 126, 128 Nervous System, 49, 95, 101, 115, 117, 120, 127 Neuroendocrine, 15, 25, 117 Neuronal, 102, 117 Neurons, 102, 105, 109, 116, 117, 127 Neurosis, 117, 120 Neurotransmitter, 44, 95, 96, 106, 109, 110, 111, 117, 118 Neutrons, 113, 117, 123 Niacin, 118, 128 Nitrogen, 51, 96, 97, 109, 118, 128 Nonverbal Communication, 118, 123 Norepinephrine, 14, 95, 96, 106, 117, 118 Nortriptyline, 12, 14, 18, 39, 118 Nuclei, 96, 114, 117, 118, 122 Nucleic acid, 118 Nucleus, 105, 117, 118, 121, 122 O Obsessive-Compulsive Disorder, 10, 15, 30, 31, 32, 61, 84, 109, 118 Ointments, 106, 118 Orgasm, 107, 118 Orthostatic, 98, 114, 118 Overdose, 15, 118 Oxidants, 61, 118 Oxidation, 98, 99, 104, 118, 119 Oxidation-Reduction, 99, 118, 119 P Paclitaxel, 19, 119 Pancreas, 95, 106, 119 Panic, 8, 11, 34, 38, 39, 53, 57, 59, 61, 63, 64, 72, 84, 109, 119 Panic Disorder, 8, 11, 34, 38, 39, 61, 63, 64, 72, 84, 109, 119 Paresthesias, 119 Paroxetine hydrochloride, 7, 19, 44, 45, 46, 47, 48, 52, 53, 54, 55, 56, 58, 59, 60, 62, 64, 119 Partial remission, 119, 124 Pathologic, 104, 112, 119, 122 Pathophysiology, 37, 119 Penis, 107, 119 Peptide, 96, 119, 122 Perfusion, 37, 119 Peripheral blood, 113, 120 Peripheral Nervous System, 107, 117, 120, 122

Phagocyte, 118, 120 Pharmaceutical Solutions, 106, 120 Pharmacokinetic, 120 Pharmacologic, 97, 110, 120, 128 Phenyl, 56, 60, 62, 120 Phenylalanine, 120, 128 Phenytoin, 25, 26, 101, 120 Phobia, 15, 32, 71, 120 Phobic Disorders, 120 Phosphorus, 100, 120 Physiologic, 96, 110, 114, 120, 124 Pilot study, 29, 120 Pituitary Gland, 104, 120 Plants, 96, 101, 102, 110, 118, 120 Plasma, 13, 97, 100, 108, 110, 111, 116, 121, 125 Platelets, 24, 33, 39, 40, 48, 121, 127 Pneumonia, 104, 121 Poisoning, 107, 113, 117, 121 Polymorphic, 50, 105, 121 Positron emission tomography scan, 32, 121 Post-traumatic, 49, 61, 121 Post-traumatic stress disorder, 49, 61, 121 Potassium, 60, 63, 116, 121, 123 Potassium hydroxide, 60, 121 Potentiating, 96, 121 Povidone, 64, 121 Practicability, 121, 128 Practice Guidelines, 80, 121 Precipitation, 49, 121 Precursor, 46, 47, 106, 107, 118, 120, 121, 128 Prefrontal Cortex, 33, 121 Presynaptic, 99, 117, 121, 122 Presynaptic Terminals, 99, 122 Probe, 15, 115, 122 Progressive, 105, 110, 122 Projection, 118, 121, 122 Prophylaxis, 53, 57, 58, 59, 122 Prospective study, 8, 122 Protein S, 66, 99, 122 Proteins, 32, 96, 97, 103, 116, 118, 119, 121, 122, 124 Protons, 111, 122, 123 Proto-Oncogene Proteins, 119, 122 Proto-Oncogene Proteins c-mos, 119, 122 Protozoa, 115, 122 Psoriasis, 17, 122 Psychiatric, 13, 18, 20, 25, 26, 115, 122, 125

136 Paxil

Psychiatry, 7, 8, 10, 11, 12, 14, 15, 16, 17, 18, 19, 21, 24, 25, 26, 30, 31, 33, 34, 44, 109, 122 Psychic, 115, 117, 122, 123, 125 Psychoactive, 9, 122, 129 Psychomotor, 101, 123 Psychophysiology, 37, 123 Psychotherapy, 10, 11, 21, 123 Public Policy, 79, 123 Purifying, 57, 123 Q Quinidine, 9, 123 Quinine, 123 R Race, 46, 47, 51, 56, 116, 123 Racemic, 46, 47, 51, 56, 123 Radiation, 108, 113, 123, 129, 130 Radiation therapy, 108, 113, 123, 130 Radio Waves, 105, 116, 123 Radioactive, 110, 111, 112, 113, 123, 130 Radiolabeled, 113, 123, 130 Radiotherapy, 100, 113, 123, 130 Randomized, 8, 11, 13, 16, 17, 18, 24, 107, 124 Rape, 121, 124 Reagent, 111, 124 Receptor, 25, 29, 31, 32, 40, 95, 98, 102, 106, 124, 125 Receptors, Serotonin, 124, 125 Recombinant, 113, 124 Rectum, 100, 106, 109, 114, 124 Recurrence, 100, 124 Refer, 1, 103, 106, 107, 109, 117, 118, 124 Refractory, 15, 124 Regimen, 40, 107, 124 Relapse, 12, 124 Remission, 11, 100, 114, 124 Resolving, 47, 124 Rheumatism, 112, 124 Rheumatoid, 118, 124 Risk factor, 122, 124 Risperidone, 20, 124 S Saliva, 9, 124 Salivary, 106, 124 Salivary glands, 106, 124 Schizoid, 124, 129 Schizophrenia, 124, 125, 129 Schizotypal Personality Disorder, 105, 124, 129 Screening, 102, 125 Secretion, 104, 110, 111, 115, 116, 125

Sedative, 96, 102, 125 Seizures, 101, 102, 120, 125 Semen, 107, 125 Senile, 52, 125 Sensibility, 97, 125 Sensitization, 37, 125 Sertraline, 9, 26, 36, 39, 66, 125 Shock, 37, 125, 128 Side effect, 44, 95, 98, 102, 125, 128 Signs and Symptoms, 124, 125 Skeletal, 97, 117, 123, 125 Sleep Deprivation, 30, 31, 125 Smoking Cessation, 100, 125 Smooth muscle, 96, 111, 125 Sodium, 116, 123, 126 Solvent, 44, 45, 48, 50, 60, 61, 62, 63, 95, 99, 108, 115, 120, 126 Somatic, 114, 120, 121, 126 Somnambulism, 18, 126 Specialist, 85, 126 Species, 107, 116, 123, 126, 129 Specificity, 95, 126 Spectrum, 115, 116, 123, 126 Spinal cord, 98, 101, 115, 117, 120, 126 Stabilization, 120, 126 Steroid, 104, 126 Stimulant, 105, 111, 115, 126 Stimulus, 108, 119, 120, 126, 127 Stomach, 95, 106, 108, 109, 111, 117, 126 Stress, 33, 35, 37, 38, 63, 64, 71, 84, 104, 114, 117, 126 Stroke, 39, 41, 78, 126 Subiculum, 111, 127 Suction, 108, 127 Suppression, 104, 127 Suspensions, 58, 127 Sympathomimetic, 105, 106, 107, 115, 118, 127 Symptomatic, 102, 127 Symptomatic treatment, 102, 127 Symptomatology, 40, 127 Synaptic, 117, 127 Systolic, 112, 127 T Tardive, 98, 102, 127 Telencephalon, 101, 127 Temporal, 97, 111, 127 Temporal Lobe, 97, 127 Thalamus, 106, 114, 121, 127 Threshold, 108, 112, 127 Thrombocytes, 121, 127 Thrombosis, 122, 126, 127

Index 137

Thyroid, 127, 128 Tissue, 97, 99, 100, 104, 108, 110, 112, 113, 115, 117, 119, 120, 125, 126, 128 Tolerance, 102, 128 Tomography, 15, 30, 32, 128 Tonic, 102, 128 Topical, 108, 128 Toxic, v, 99, 115, 121, 128 Toxicity, 34, 40, 128 Toxicokinetics, 128 Toxicology, 80, 128 Transfection, 99, 128 Translation, 96, 128 Transmitter, 95, 99, 106, 115, 118, 128 Trauma, 37, 128 Treatment Outcome, 31, 128 Tricyclic, 96, 102, 128 Tryptophan, 11, 26, 103, 125, 128 Tyrosine, 25, 106, 128 U Unconscious, 112, 128 Urinary, 107, 128 Urine, 107, 113, 128 V Vagina, 128, 129

Vaginal, 18, 129 Vasodilatation, 101, 129 Vasodilator, 106, 111, 129 VE, 9, 129 Veins, 100, 129 Venlafaxine, 8, 24, 129 Venous, 100, 122, 129 Venous blood, 100, 129 Ventricle, 97, 111, 127, 129 Venules, 100, 129 Verapamil, 32, 129 Vesicular, 26, 129 Veterinary Medicine, 79, 129 Virulence, 128, 129 Virus, 113, 129 Vitro, 129 Vivo, 129 W War, 121, 129 Weight Gain, 20, 129 White blood cell, 97, 114, 129 Withdrawal, 15, 49, 129 X X-ray, 52, 113, 123, 129, 130 X-ray therapy, 113, 130

138 Paxil

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