Pharmacology

Straight Talk About Psychiatric Medications for Kids

Straight Talk About Psychiatric Medications for Kids

Wilens TE. New York: The Guilford Press; 1999

ISBN 1-57230-204-6 (paper)

In general, psychiatry has come a long way — from a pure psychoanalytical focus to a strong medical-neurobiological approach to treating psychiatric disorders. It is now well known in our clinical practice and in psychiatric literature that biologically based treatment with psychotropic medications, combined with other traditional and non-medical treatments, has proven superior to either treatment modality used alone. Similarly, child psychiatry and psychopharmacology have gained significant positions, both within the fields of medicine and general psychiatry.

Psychiatric conditions are recognized earlier in children who present with behavioural/emotional and developmental problems. These special children are more at risk of academic difficulties and parental rejection. In the best interests of the child and family, the challenge facing child psychiatrists is to provide an integrated assessment from a bio-psychosocial perspective before proceeding with specific treatment modalities; treatment should be conducted within interdisciplinary teams in which parents and their children are encouraged to participate actively. Physicians can expect parents and youth to be more active in questioning and decision-making. Medication may be indicated if behaviour modification and other therapies achieve only partial success; however, parents may still be reluctant to accept medication trials as a first-line approach. This book fills a need as a comprehensive reference source on current psychiatric medications.

The author is a well-known child psychiatrist and associate professor of psychiatry at Harvard Medical School. He specializes in pediatric and adult psychopharmacology and addiction psychiatry, and does his clinical work at Massachusetts General Hospital. He has published widely on psychiatric medications and their uses.

This book is the result of Wilens’ extensive clinical experience; it focuses on questions typically raised by parents concerning the assessment and treatment of their children. I believe it can serve as a useful information package for parents, educators and trainees in the field of psychiatry.

The contents are divided into three main parts. Part I describes and explains in straightforward language the general clinical processes of psychiatric evaluation, diagnosis and treatment plan. A central theme is that, as parents become familiar with the treatment process, they learn the importance of working collaboratively with the psychiatrist treating their child.

Part II informs the reader about common childhood psychiatric disorders as well as neurobiological conditions such as temporal lobe epilepsy, tic disorders, Tourette’s syndrome and organic mental disorders. For each condition, the author succinctly summarizes basic factual information; this is followed by information about coexisting emotional/behavioural conditions. The range of dosages is given for different medications.

With this basic understanding, the reader is prepared for Part HI, in which each class of psychotropic medications used in children is described with respect to names, dosages, indications and contraindications. Whenever needed, specific baseline testing or monitoring is also included.

Definitions of medical terms and expressions are interspersed appropriately in the text and framed in double lines for easy reference. Questions are printed in bold. Medications in each class are presented in a table form with names, preparations and strengths.

The last 37 pages include an appendix, medication log, resources, bibliography and index. The appendix is a table listing both generic and brand names of medications, with strengths and preparations. I found the example of a completed medication log useful for keeping track of each medication with respect to start date, dosage, response, side effects and comments.

The section on resources supplies the names and addresses of community and organizational supports within the United States, broken down by general mental health and specific disorders. The bibliography lists journal articles and books by recognized clinicians in different disorders. The section on tics and Tourette’s syndrome mentions 4 excellent references, but could have included Tourette Syndrome & Human Behavior, by David E. Comings, which is widely used by parents and professionals.

The author does not mention the use of psychiatric medication in preschool children (ages 2 to 6 years). Parents of these children are even more reticent to accept medication, even when their child’s condition is severe. There is no information on treating children with the amino acid tryptan (L-tryptophan) for various conditions. Also, the text does not clearly convey the serious potential risk of dependence on benzodiazepines. For this reason, it is better to avoid the use of benzodiazepines in children and youth. It is known that they may mix these prescribed drugs with other substances once the body develops a tolerance.

Overall, this book may enable mental health professionals to feel confident about addressing parents’ concerns and questions regarding psychiatric medications. It may save time for health care providers by giving parents the understanding they need to collaborate with professionals in the treatment of their child with psychiatric and mental health problems. Despite some weaknesses, the book does provide an abundance of valuable information. In clinical practice, however, it should be used as an adjunct to current literature on each drug in question, providing the reader with a balanced perspective.

Pharmacology of Anxiolytic Drugs

Pharmacology of Anxiolytic Drugs. WHO Expert Series on Neuroscience, vol. 3

Racagni G, Masotto C, Steardo L

Seattle (WA): Hogrefe and Huber; 1997. 132 pp. with index

ISBN 0-88937-088-5 (cloth)

This monograph forms part of the World Health Organization’s expert series in neuroscience, which is intended to help prevent or control mental neurological disorders and psychosocial problems, as well as to ensure broad use of mental health knowledge in general health care within WHO member states. It is indeed a textbook of pharmacology and should be viewed as such.

The authors must be world renowned in the field of pharmacology and its clinical application, although I could find only one citation by one of the authors (a publication in Nature in 1979) through MEDLINE. As well, the authors do not cite themselves in the book, indicating either that they are modest or that their publications are now aged. The University of Milan, however, has a reputation for expertise in pharmacology.

The book begins with a succinct history of the search for anxiolytics. The comprehensive contents of the book are then divided into 4 groups. Group 1, on benzodiazepines, is the most comprehensive of the chapters and includes a detailed description of each of the benzodiazepines, including their 2-dimensional chemical formulae. There is an extensive discussion of action, side effects, dependance and interactions. Group 2 discusses compounds with benzodiazepine-like activity, and details agonists, partial-agonists and antagonists. Group 3 reviews compounds that act on nonbenzodiazepine receptors and includes a large discussion of the role of serotonin in anxiety. Group 4 considers the role of antidepressants as anxiolytics and includes tricyclic antidepressants, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, α2-adrenergic blockers and β-blockers.

Only generic drug names are used throughout the book.

This book is a very comprehensive, well-organized and crisp discussion of anxiolytic drugs, and includes scientifically backed clinical use. Remember, the title is Pharmacology of Anxiolytic Drugs, and so the rather dry chemical formulae, pharmacokinetics and pharmacodynamics seem clinically sterile. The authors include substances that we prescribe routinely as well as medications that are not very commonly used in this country but may be in other parts of the world.

There are other texts, such as those by Goodman and Gilman or by Schatzberg and Nemeroff, that are more enjoyable to read, but they are not as complete as this book, and they cannot be held in one hand. This book is not a light read, but is a good, comprehensive reference.

My main criticism is that there is a lack of reference to the clinical situation, but then, this is a textbook of pharmacology.

The readership is meant to include nurse practitioners, social workers, family physicians, and others, but I believe they would use this book only as a reference text. Psychiatrists, residents in psychiatry and anesthetists would find this book quite valuable.

Clinical Guide to Alcohol Treatment

Clinical Guide to Alcohol Treatment: The Community Reinforcement Approach

RJ Meyers, JE Smith

New York: Guilford Press; 1995. 215 p

Robert Meyers from the Centre on Alcoholism, Substance Abuse and Addictions (CASAA) and Jane Smith from the Department of Psychology, both from the University of New Mexico, have authored a pragmatic “how-to” instruction book on the Community Reinforcement Approach (CRA) to alcohol treatment. CRA is listed in the US Institute of Medicine’s report on alcohol problems as a contingency management approach designed to provide focused behavioral training to persons with chronic alcohol problems (Institute of Medicine 1990). This approach remains unfamiliar to many clinicians in the field although several grants from the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and National Institute on Drug Abuse have been provided to enrich its research basis.

The 1 st chapter outlines the approach’s empirical pedigree dating back to the work of NH Azrin and his group in 1973. The reinforcers used were access to family, to jobs, and to friends, which were contingent on sobriety. In a series of trials, CRA procedures improved the outcome of traditional 12-step programs, monitored disulfiram compliance, and enhanced an alcohol-free recreational environment as well as the involvement of concerned others. These procedures have also been applied to the management of cocaine and heroin abusers and, more recently, to an alcohol-abusing homeless population.

The book’s main contribution lies in the next 10 chapters. Five chapters provide detailed instruction in the CRA assessment procedure, an intriguing approach to facilitating a client’s acceptance of the need for sobriety through a contractual “time-limited sampling” period, the optimal use of disulfiram, and the planning of a treatment protocol using a quality of life scale and identification of counselling goals. The remaining chapters describe procedures to be used for behavioral skills training as well as coping strategies at work, in one’s social interactions and significant relationships, and in relapse prevention.

The highlights of the book for me were the tables appended at the end of each chapter that could be readily adapted by therapists to their own practice. The book is a good primer for those interested in developing their cognitive-behavioral skills with substance abusers. Some procedures may be more controversial or dated than others. For example, recent studies have provided mixed evidence regarding the usefulness of disulfiram (Institute of Medicine 1990). Will the use of naltrexone replace disulfiram as a preferred pharmacotherapy?

As highlighted by the Director of the Research Division at CASAA, Dr WR Miller, many of the procedures included in the original CRA trials, such as motivational preparation and early relapse prevention strategies, have become important elements in today’s treatment programs and have gained more recognition than their predecessors. Elements of the CRA have been incorporated as part of the cognitive-behavioral intervention to be tested in Project MATCH (1994), the current NIAAA-funded multisite clinical trial of patient-treatment matching.

This book’s content is suitable for a multidisciplinary team dedicated to the field of addiction and for the psychiatric resident or psychiatrist searching for ways to enhance his or her skills with this challenging population. The cost of the book is reasonable.

Clinical Evaluation of Psychotropic Drugs: Principles and Guidelines

Clinical Evaluation of Psychotropic Drugs: Principles and Guidelines

RF Prien and DS Robinson, editors

New York: Raven Press; 1994, 669 pages

This book reflects several decades of active development in psychotropic drug evaluation. The first modern, randomized, double-blind controlled trial of a psychotropic drug was conducted in the early 1950s (Schou’s evaluation of anti-manic lithium). Since the first methodological book on evaluation, edited by Cole and Gerrard (1959), several international statements of expectations have been published describing how psychotropic drug evaluations should take place. The present volume represents a culmination of the US national effort to establish guidelines for clinical evaluation of psychotropic drugs. Academic, clinical, pharmaceutical, regulatory and public health sectors, as well as several other disciplines contributed to this unfolding over the years.

This book was initiated in 1990 by the establishment of a task force on guidelines for clinical evaluation of psychotropic drugs; the American College of Neuropsychopharmacology (ACNP) and the National Institute of Mental Health (NIMH) collaborated. While the recent international volume (Grof et al 1993) focuses on education, the Prien and Robinson book appears more appropriate for experienced investigators. It often deals with issues and problems that would confound the novice looking for guidance in a maze of clinical trials.

Clinical Evaluation of Psychotropic Drugs: Principles and Guidelines is a resource that reflects the knowledge and experience of a wide group of US experts. The contributing authors number exactly 100, and the list reads almost like a “Who is Who” in US psychopharmacology. The book is as multi-authored as one could possibly imagine. An editorial group provided overall leadership. The ACNP taskforce advised on content and authorship of the book, and reviewed initial chapter drafts. Subsequent drafts were circulated to outside reviewers specializing in particular fields. Those of us foolish enough to engage in multi-authored writings will appreciate the challenges and the extensive nature of this process.

The book is divided into three main sections of increasing length. The first section, “Historical Perspectives”, describes the context of the book by providing a historical overview of clinical psychopharmacological research and guidelines. It also describes the decision-making process of establishing the efficacy and safety of psychotropics. The second section, “General Principles in the Evaluation of Psychotropic Drugs”, contains a broad outline of developments and issues of clinical methodology, and provides direction in research principles, study design and implementation, presentation of study findings, and ethical considerations involving drug evaluations. The third and most extensive section,”Specific Patient Groups: Application of General Methodologic Principles”, addresses methodologic developments and recommends clinical evaluation of specific diagnostic and age populations. This section builds on the ideas expounded in the preceding sections. A predecessor of this book, entitled Principles and Problems in Establishing the Efficacy of Psychotropic Agents and edited by Jerome, Levin, Burtrum, Schiele, Lorraine and Bouthelet, was published in 1971. The present book can be seen as an extensive revised and updated version of that first comprehensive volume, and it documents the advancement in the clinical trial methodology of psychopharmacology over the past 25 years.

This outstanding book will be essential for anyone actively involved in psychotropic drug trials. I found three parts particularly intriguing. First, the sections on ethical and legal considerations, which have become particularly heated during this time of political correctness, are of great interest. Second, the sections on maintenance (prophylactic) trials in general and in specific patient groups are also fascinating. If recent developments are indicators, there will be a major expansion in die area of testing, in particular because of the clinical need, and the widespread use of long-term treatments. Third, some of the innovative ideas that may improve and hasten the evaluation of new drugs are of interest. The desire for innovative approaches is driven by a new emphasis on cost containment as well as by the increasing importance awarded to treatment effectiveness, rather than relying solely on randomized, controlled trials for proof of efficacy.

It is clear that we are going through a stage of developing new methodology, and are questioning older ideas. It seems likely that in the future we will view the traditional, randomized, clinical trial as a necessary but insufficient technique in providing comprehensive evaluation. The Bayesian approach is becoming more common in clinical trials, with a de-emphasis on the frequentist approach. Increased attention is being paid to the problems of statistical analysis of longitudinal data, and the techniques of integrating information through meta-analysis. Researchers have become increasingly concerned about the limitations of generalized clinical trials in clinical practice. New strategies, envisaged in the World Health Organization (WHO) guidelines, are being proposed, ranging from the value of vigorously-collected observational data to the use of clinical databases and new strategies of cross design synthesis.

In a book of this size, with several contributing authors, it is to be expected that everything will not emerge perfectly, and that one will encounter allusions to the same issues a number of times (e.g., the complex placebo issue). It is also inevitable that, when a book is in preparation for several years, certain issues are dated by the time of publication. This is the case with the incorrect statement that the regulatory agencies in Europe do not require proof of prophylactic efficacy for new antidepressants. It is also of interest that the authors, although referring to the traditional phases of evaluation, have not structured the book following the four classical phases, as in previous books on clinical trials. Although this excellent book could not be useful to a psychopharmacological novice, it will be of much value to experienced investigators for years to come.

5-HT1A Agonists, 5-HT3 Antagonists and Benzodiazepines: Their Comparative Behavioral Pharmacology

5-HT1A Agonists, 5-HT3 Antagonists and Benzodiazepines: Their Comparative Behavioral Pharmacology

RJ Rodgers and SJ Cooper

New York NY: John Wiley, 387 pp, 1991

Dr. Rodgers and Dr. Cooper have done a masterful job in gathering seminal information towards the understanding of the anxiolytic activities of serotonin, agonists, serotonin antagonists and benzodiazepines. Benzodiazepines are prescribed extensively in our society for anxiety disorders. Given the addiction potential associated with benzodiazepines, the need is great to find other types of medications to treat patients with anxiety disorders. This book attempts to empirically compare the anxiolytic medications currently available and to provide a focus for continuing research. While the core of the book is devoted to basic science, including a number of chapters on animal models and experimentation, the clinical aspects of pharmacology are not ignored. In chapters 11 and 12, the abuse, dependence and withdrawal potential of benzodiazepines are discussed and in chapter 13, Edward Schweizer and Karl Rickels review the efficacy of serotonergic anxiolytics.

An excellent discussion of benzodiazepine receptors and their ligands is found in the first chapter. In the past ten years there has been an explosion of knowledge in the pharmacology and chemistry of benzodiazepine receptors and we are now able to clone them. This book helps to explain why certain drugs are agonists, antagonists, partial agonists and inverse agonists. The 5-HT receptor family and their ligands, distribution and receptor-effector coupling are covered in the second chapter. Recent information on the anxiolytic effects of serotonergic-type drugs is promising, particularly the 5-T1A agonists and 5-HT3 antagonists.

This text is not meant for recreational reading since it contains a great deal of basic science. The style of writing produces consecutive and somewhat unrelated chapters written by different authors, each an expert in his or her field. Basic scientists will find this text informative and an excellent reference since long lists of articles are given at the end of each chapter. As well, clinicians dealing with anxiety disorders, in particular those who administer benzodiazepines and serotonergic-regulating medication, would benefit from reading this book so as to be able to properly use these medications. Knowledge in this field advances at a rapid rate; this pharmacological review will help both scientists and clinicians keep up-to-date.

Use of Drags in Psychiatry & Clinical Handbook of Psychotropic Drugs

Use of Drags in Psychiatry: A Handbook

Emmanual Persad and Vivian Rakoff

Hans Huber Publishers, 157 pp., 1987

Clinical Handbook of Psychotropic Drugs, 3rd Edition

Kalyna Z. Bezchlibnyk-Butler and J. Joel Jeffries

Toronto ON: Hogrefe and Huber Publishers, 83 pp., 1992

These books are from the Clarke Institute of Psychiatry and the University of Toronto and both are very practical and excellent guides to the safe and intelligent use of psychotropic drugs.

The first book is aimed at the use of drugs and covers all the various classes including the long acting neuroleptics. It also has a chapter on diagnosis and management of neuroleptic-induced movement disorders.

Each chapter has a different author but a general format is followed giving indications, contraindications, dosage forms, major side effects and many practical suggestions for drug usage.

There are chapters on ECT, the pharmacological treatment of offensive behavior, the sodium amytal interview and a very informative chapter on questions patients ask about psychiatric medications.

Each chapter ends with suggested readings which are well chosen and in line with the purpose of the book which, as the editors point out, is a handbook useful for daily reference and an up-to-date guide to empirical drug treatment in psychiatry. The editors refer to the delay between writing and publication. It is hoped that another edition will emerge soon which will include some of the more recent additions to drug treatment in psychiatry, noteably risperidone, moclobemide, fluoxetine and fluvoxamine.

The second book is in a larger format measuring 11″ by 9″ with a spiral binding that makes it possible to lay the large pages open.

This book also covers all the psychotropic drugs. The format includes many tables and charts which make it very easy to use as a reference, particularly for making comparisons and indications for drugs of any particular class. It includes the more recent antidepressants.

The editors describe this book as user friendly and I found it lived up to this description. It was very easy to look up very specific detailed points and find the answer very rapidly in the text or in one of the tables.

These are two good basic pratical books on psychotropic drugs. I recommend both books for medical students, mental health workers, pharmacists, family physicians and general psychiatrists who wish to keep abreast of the intelligent and safe use of psychotropic drugs.

Clinical Evaluation of Psychotropic Drugs for Psychiatric Disorders

Clinical Evaluation of Psychotropic Drugs for Psychiatric Disorders; Principles and Proposed Guidelines, Volume 2

P. Grof et al. WHO expert series on biological psychiatry

Hogrefe and Huber Publishers, 202 pp, 1993

In the past decade, clinical psychopharmacology has entered an exciting era of development, rising hopes and expectations. Second generation anti-depressants became the first choice drugs, new atypical antipsychotic drugs are beginning to make their mark and the menu of anxiolytics seems to cater to all tastes. However, this spectacular growth and success represent the end result of a journey through a complex and winding path of psychotropic drug development and evaluation. In the process, conceptual, methodological and ethical issues have been explored, debated and at times resolved. The accumulated literature on the principles and practice of psychotropic drug research is widely dispersed among pharmacology texts, clinical trials monographs, statistical treatises and occasionally psychiatric journals. There have been few works solely dedicated to this subject; the publication of this book is a modest attempt to fill this void.

The purpose, background, development, format, scope and limitations of the document are stated in the brief, well written introduction. This is followed by an overview of the drug evaluation process, summarizing the phases of drug development, testing and monitoring, and discussing the surrounding methodological and ethical issues. This would certainly help the novice to gain a comprehensive picture of the subject and lays a blueprint for the rest of the document. The successive phases of drug evaluation are succinctly reviewed in the first four chapters and special issues involving children, elderly and transcultural studies are addressed in the remaining three chapters. The nuts and bolts of clinical trials are well covered here, discussing the details of protocol preparation, varieties of study designs, sampling techniques, aspects of measurement and data gathering. The liberal use of tables, sub-headings and footnotes has helped to neatly summarize the abundance of information and facilitate an easy access for quick reference.

The aim apparently was to consolidate the existing, established knowledge on the subject, avoiding controversies. Thus, spelling out the scope and limitations of the document, the authors proceeded to organize the information with a logical plan and lucid style. The selected list of references included, mainly for the scales and instruments, help students and young researchers to find their way around the confusing field of measuring mental phenomena.

However, achieving consensus and eagerness to avoid controversy has somewhat limited the scope and impact of the book. The approach is too practically oriented, dealing exclusively with methodological details and execution of clinical trials. Conceptual issues are mostly avoided. A chapter on the contemporary confusion surrounding psychiatric classification, diagnosis and measurement would have been a valuable addition. The book would have benefited from an annotated bibliography at the end of each chapter.

In spite of these limitations, the book certainly fulfils its purpose, serving as a useful reference guide for students of psychopharmacology, pharmacy and psychiatry as well as clinical investigators. The book is unconditionally recommended for all libraries but individuals tempted to buy it should first check the price from their local book stores. In Toronto, the quoted price of $44.00 is slightly expensive. WHO documents, widely referred to in the developing countries, should no doubt be cheaper.

Molecular and Cellular Approaches to the Treatment of Neurological Disease

Molecular and Cellular Approaches to the Treatment of Neurological Disease

Stephen G. Waxman

New York, NY: Raven Press, 415 pp, 1992

This book offers a comprehensive summary on current state of the art and future directions for treatment of neurological disease at the neuronal level. While generally well written and comprehensive, some portions are highly technical and somewhat difficult to follow.

The book opens with a general overview of molecular and cellular organization, and sketches implications for new therapeutic regimen. This section is well written but suffers because the explanations for the illustrating figures are much too wordy. This section does however offer an important overview of the field and fulfils its purpose well.

Section 2 deals with mechanisms of neuronal injury and death. Discussion spans from the receptor pharmacology of glutamate to the role of calcium in glutamate neurotoxicity. Further discussion of glutamate receptors and excitotoxicity is followed by a summary of the consequences of hypoxic insult to the mammalian central nervous system. The following segment, “Mitochondrial Dysfunction as a Mechanism of CNS Injury”, offers insight into the role of documented or postulated mtDNA mutations in human CNS disease. The important topic of free radicals in CNS injury concludes this segment.

The next section, “Neuronal Injury in Specific Disease States”, is a logical sequitur. This particular subject is again approached comprehensively, but the chapter on the role of excitotoxins in heredito-degenerative neurologic diseases by Anne Young stands out because of its clarity and thoughtful treatment of the subject.

The fourth section on therapeutic strategies is particularly timely. While all chapters in this section are of excellent quality, the inclusion of a chapter on the design of clinical trials attests to the editors commitment to treat this subject matter comprehensively.

A section on cellular and molecular replacement concludes the book. All three chapters in this section are intriguing, worth while and add to the considerable value of this book. The only concern one may have is that the chapter on preliminary results on the use of human fetal mesencephalic tissue in the treatment of Parkinson’s disease has no fewer than 18 authors. This appears excessive for a book chapter. This concern is somewhat mitigated by the excellent quality of the chapter, both with respect to the scholarly content and writing style.

The book concludes with a discussion of the prospects for neuronal replacement in neurodegenerative disease which offers a brief but adequate overview of the current state of the art as well as future prospects.

In summary, Dr. Waxman should be congratulated for bringing together a world renowned group of experts dealing with a highly complicated subject in a book which is both enjoyable to read and of excellent scholarly quality. Although the subject matter is by definition complex, the editor and contributors to this book have succeeded in providing a concise summary of the current knowledge in this field. As such, I found the book extremely useful and would highly recommend it to the relatively limited audience dealing with experimental therapeutic strategies in this context.

Neurotransmetteurs. Bases neurobiologiques et pharmacologiques

Neurotransmetteurs. Bases neurobiologiques et pharmacologiques

Paris: Masson, 272 pp, 1992

Cet ouvrage est divisé en trois parties. La première traite des aspects morphologiques de la neurotransmission (organisation et structures des synapses, cycle d’utilisation des neurotransmetteurs, etc.), des ses aspects fonctionnels (récepteurs, seconds messagers, canaux ioniques, etc.), de même que des méthodes utilisées en recherche (biochimie, électrophysiologie, étude du comportement, etc.). L’exposé est très complet, les schémas utilisés sont simples, clairs et pédagogiques. La seconde partie utilise les concepts décrits dans les chapitres précédents afin de présenter séparément les caractéristiques de chacun des neuromédiateurs «classiques» (monoamines, acétylcholine, GABA, glutamate, etc.), ainsi que ceux qui n’ont suscité un intérêt que plus récemment (par exemple, les neuropeptides). Les différents chapitres qui composent la seconde partie procèdent d’une schématisation nécessairement très simplifiée de résultats appartenant à un domaine qui évolue d’une façon extrêmement rapide. Dans la troisième partie du livre, les auteurs illustrent la question des perturbations de la neurotransmission en analysant superficiellement certaines pathologies du système nerveux central.

Ce livre synthétique et pédagogique pourrait être décrit comme une petite encyclopédie spécialisée sur la neurotransmission; il s’adresse donc aux étudiants universitaires de premier et de deuxième cycle, de même qu’aux cliniciens et chercheurs non familiers avec ce domaine. Aucune référence bibliographique ne vient appuyer le texte, mais les auteurs suggèrent une liste (malheureusement non commentée) de 11 manuels de référence générale. L’utilité de la troisième partie pourra sembler marginale, mais puisqu’elle n’occupe que 50 des 253 pages du livre, sa qualité illustrative en justifiera la présence auprès de certains. En somme, il s’agit d’un très bon livre d’introduction sur la neurotransmission dans le système nerveux central; sa lecture permettra aux non initiés de mieux comprendre les textes plus ardus sur la question.

Novel Antipsychotic Drugs

Novel Antipsychotic Drugs

H. Y. Meltzer

New York, NY: Raven Press, 288 pp., 1992

Traditionally, the development of antipsychotic drugs has entailed looking for agents that produced catalepsy and blocked amphetamine-induced stereotypic movements in rodents. This produced a generation of drugs that were therapeutically antipsychotic but produced unacceptably high rates of neurological adverse effects. The atypical antipsychotics are a new generation of drugs that, through novel pharmacological properties, promise a lower rate of extrapyramidal side-effects and, in some cases, therapeutic superiority over the typical agents.

This volume, edited by psychiatrist and psychopharmacologist Herbert Meltzer, represents the proceedings of a symposium held in late 1990 which detailed the atypical agents being developed. For the most part, the volume is a status report on agents in various stages of development. These include clozapine and the related drug amperozide, the substituted benzamides remoxipride and raclopride, a number of dopamine agonists; drugs that mediate glutamine, “sigma” receptor antagonists, and serotonin antagonists such as respiridone and ondansetron. There are also three conceptual articles: Meltzer’s review of research into the efficacy and favorable extrapyramidal side-effect profile of clozapine, Philip Seeman’s review of receptor selectivities, which unfortunately predates the work on the D4 receptor, and Daniel Casey’s review of classification and directions for future research.

Although some of the articles appear to have been updated with material and references more recent than 1990, most of the book suffers from being a step out of date. Despite this, I found the volume more helpful than I anticipated, particularly the articles by Casey and Meltzer. This volume may be most significant as a historical work, since it heralds a welcome turning point in the pharmacotherapy of schizophrenia. For the first time, there is the promise of agents that offer novel therapeutic profiles, without the disabling neurologic effects we and our patients have had to learn to live with. Not only do these agents offer optimism, they also lead us to new models of pathophysiology for understanding schizophrenia and related disorders.