The Use and Misuse of. Sleeping Pills. -A Clinical Guide-

Transcription

1 The Use and Misuse of Sleeping Pills -A Clinical Guide-

2 Head of Hypnos (Photograph courtesy of the British Museum)

3 The Use and Misuse of Sleeping Pills --A Clinical Guide-- Wallace B. Mendelson, M. D. National Institute of Mental Health Bethesda, Maryland Plenum Medical Book Company New York and London

4 Library of Congress Cataloging in Publication Data Mendelson, Wallace B The use and misuse of sleeping pills. Includes bibliographical references and index. 1. Hypnotics. 2. Insomnia - Chemotherapy. 3. Medication abuse. 1. Title. [DNLM: 1. Hypnotics and sedatives - Pharmacodynamics. 2. Hypnotics and sedatives - Adverse effects. 3. Insomnia - Drug therapy. QV85 M537uj RM325.M46 615' ISBN-13: e-isbn-13: DOl: 10_1007/ Plenum Publishing Corporation Softcover reprint of the hardcover 1st edition West 17th Street, New York, N.Y Plenum Medical Book Company is an imprint of Plenum Publishing Corporation All righ t s re serve d No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher

5 Preface Hypnos (the Greek god of sleep) and Thanatos (death) were the twin sons of Nyx, the goddess of night (Fox, 1964). Hypnos lived in a dusky valley in the land of the Cimerians, watered by Lethe, the river of forgetfulness. He brought sleep to both men and gods, and sometimes sent his sons Morpheus, Icelus, and Phantasus to appear in dreams. At the door of his abode grew poppies and other herbs which induce sleep (Hamilton, 1961). This book deals with these herbs and their subsequent imitations. Before launching into an examination of hypnotics, it might be well to comment briefly on the manner in which this was written, and to acknowledge the help of a number of individuals. My intention was that this be useful not only for the physician or scientist, but also for the student. Thus each chapter contains an introductory section which provides background material. Chapter 3, for instance, describes the general principles of drug absorption, distribution, and metabolism before discussing the pharmacologic properties of each hypnotic. In addition, each chapter concludes with a section which summarizes the main issues. This book was made possible by the continued encouragement and many helpful suggestions of Dr. Richard Jed Wyatt and Dr. J. Christian Gillin. Dr. William E. Bunney has been supportive throughout the course of this work. A number of persons were kind enough to comment on various chapters, for which thanks go to Drs. William C. Dement, David C. Kay, Daniel F. Kripke, William Potter, Seymour Perlin, Laurence S. Jacobs, Donald W. Goodwin, and Johanna S. R. Mendelson. My interest in this area was stimulated by working with the Institute of Medicine on a study of insomnia and hypnotics, for which I am grateful to Dr. David A. v

6 vi PREFACE Hamburg and the Institute staff. Miss Susan Dawson very kindly assisted in the preparation of the manuscript. Lastly, this book has been written by me as a private individual. The views expressed do not necessarily reflect those of the Public Health Service, the National Institute of Mental Health, or the Institute of Medicine. WALLACE B. MENDELSON Bethesda, Maryland

7 Contents 1 Basic Concepts about Sleep and Insomnia... 1 History The Sleep Stages Waking NonREM Sleep Stage Stage Stages 3 and REM Sleep Influences on the Appearance of Sleep Stages Physiologic Regulation of Sleep Passive versus Active Model The Neurotransmitters Circulating Humors.... Hypnotics and Sleep Regulation.... Sleep Deprivation.... The Need for Sleep.... Insomnia.... Summary and Conclusions The Prevalence of Sleep Disturbance and Hypnotic Use Surveys of Reported Sleep Disturbance Types of Sleep Complaints vii

8 viii CONTENTS Surveys of Hypnotic Use... " Patient-Physician Interaction Prescriptions for Outpatients Prescribing Hypnotics in Hospital Practice..., 36 Summary and Conclusions Pharmacology of Prescription Hypnotics Pharmacologic Considerations Barbiturates History Actions Structure and Classification Alterations in Metabolism and Excretion: lllness, Old Age, Enzyme Induction Chronic Administration Benzodiazepines History Flurazepam Nitrazepam Temazepam Other Properties of Benzodiazepines Nonbarbiturate, Nonbenzodiazepine Hypnotics... " Chloral Hydrate and Derivatives Methaqualone Piperidinedione Derivatives Glutethimide Methyprylon Ethchlorvynol Ethinamate Summary and Conclusions... : The Efficacy of Hypnotics Methodologic Considerations Possible Measures of Efficacy Subject Selection Other Methodological Issues Efficacy Studies in Specific Disorders... 67

9 CONTENTS ix Reference Section: Efficacy Studies in Normal Volunteers and "Insomniacs" Barbiturates Benzodlazepines Flurazepam... " 72 Nitrazepam... '.'... " 76 Temazepam Nonbarbiturate, Nonbenzodiazepine Hypnotics Chloral Hydrate Methaqualone Glutethimide Methyprylon... : Ethchlorvynol..., 83 Summary and Conclusions Suicide and Hypnotics... ~ Incidence Traits of the Victim Clinical Toxicity Barbiturates Benzodiazepines.... Nonbarbiturate, Nonbenzodiazepine Hypnotics.... Chloral Hydrate.... Methaqualone.... Glutethimide..... Ethchloroynol.... Treatment.... Preven tion.... Summary and Conclusions... " Residual Daytime Effects of Hypnotics Electrophysiologic Residual Effects Psychomotor Measures of Residual Effects subjective Evaluation of Daytime Performance Hypnotics and Driving Summary and Conclusions

10 x CONTENTS 7 Interactions with Ethanol General Considerations Barbiturates Benzodiazepines Nonbarbiturate, Nonbenzodiazepine Hypnotics Chloral Hydrate Methaqualone Glutethimide Summary and Conclusions Hypnotic Dependence Classical Drug Abuse Dependence in Medical Practice Dependence on Extremely Large Doses Prolonged Use of Recommended Doses Incidence and Contributing Factors Drug Qualities Related to Prolonged Use Summary and Conclusions Hypnotics and the Elderly Pharmacology in the Elderly Efficacy Studies Toxicity Summary and Conclusions Other Pharmacologic Approaches Over-the-Counter Hypnotics Compounds Used in OTC Hypnotics Methapyrilene Scopolamine Bromides Efficacy Federal Regulation

11 CONTENTS xi L-Tryptophan Ethanol Summary and Conclusions Nonpharmacologic Treatment of Insomnia Counseling and Psychotherapy Behavioral Therapies General Considerations Relaxation Procedures Conditioning-Derived Therapies Attributional Therapy Behavioral Self-Management... "..., Summary and Conclusions Conclusion: Implications for Medical Practice..., 177 Summary Approach to the Insomniac Patient Evaluation The Decision Whether to Give Hypnotics Acute or Intermittent Insomnia Chronic Insomnia When Hypnotics Are Prescribed References Index