The Use and Misuse of Sleeping Pills -A Clinical Guide-
Head of Hypnos (Photograph courtesy of the British Museum)
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
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'.782 79-21856 ISBN-13: 978-1-4684-3649-5 e-isbn-13: 978-1-4684-3647-1 DOl: 10_1007/978-1-4684-3647-1 1980 Plenum Publishing Corporation Softcover reprint of the hardcover 1st edition 1980 227 West 17th Street, New York, N.Y. 10011 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
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
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
Contents 1 Basic Concepts about Sleep and Insomnia... 1 History.... 1 The Sleep Stages.... 3 Waking.... 3 NonREM Sleep.... 4 Stage 1.... 4 Stage 2.... 4 Stages 3 and 4.... 5 REM Sleep.... 6 Influences on the Appearance of Sleep Stages.... 7 Physiologic Regulation of Sleep.... 9 Passive versus Active Model.... 9 The Neurotransmitters..................................... 10 Circulating Humors.... Hypnotics and Sleep Regulation.... Sleep Deprivation.... The Need for Sleep.... Insomnia.... Summary and Conclusions.... 12 12 13 15 16 23 2 The Prevalence of Sleep Disturbance and Hypnotic Use...... 25 Surveys of Reported Sleep Disturbance... 25 Types of Sleep Complaints.................................... 30 vii
viii CONTENTS Surveys of Hypnotic Use... ".......... 31 Patient-Physician Interaction.................................. 33 Prescriptions for Outpatients.................................. 35 Prescribing Hypnotics in Hospital Practice..., 36 Summary and Conclusions.................................... 36 3 Pharmacology of Prescription Hypnotics.................... 39 Pharmacologic Considerations................................. 40 Barbiturates... 45 History... 45 Actions... 47 Structure and Classification................................. 47 Alterations in Metabolism and Excretion: lllness, Old Age, Enzyme Induction..... 50 Chronic Administration.................................... 51 Benzodiazepines............................................. 52 History........................................... 52 Flurazepam... 53 Nitrazepam... 55 Temazepam... 55 Other Properties of Benzodiazepines... 55 Nonbarbiturate, Nonbenzodiazepine Hypnotics... ".... 56 Chloral Hydrate and Derivatives... 56 Methaqualone............................................. 58 Piperidinedione Derivatives................................. 59 Glutethimide............................................. 59 Methyprylon............................................. 60 Ethchlorvynol........................................ 60 Ethinamate................................................ 61 Summary and Conclusions... :............. 61 4 The Efficacy of Hypnotics................................. 63 Methodologic Considerations.................................. 64 Possible Measures of Efficacy... 64 Subject Selection... 65 Other Methodological Issues................................ 66 Efficacy Studies in Specific Disorders... 67
CONTENTS ix Reference Section: Efficacy Studies in Normal Volunteers and "Insomniacs"... 69 Barbiturates............................................... 70 Benzodlazepines........................................... 72 Flurazepam... " 72 Nitrazepam... '.'... " 76 Temazepam................................... 77 Nonbarbiturate, Nonbenzodiazepine Hypnotics... 78 Chloral Hydrate.......................................... 78 Methaqualone............................................ 79 Glutethimide............................................. 81 Methyprylon... :.......... 82 Ethchlorvynol..., 83 Summary and Conclusions.................................... 83 5 Suicide and Hypnotics... ~....... 85 Incidence.................................................... 85 Traits of the Victim........................................... 89 Clinical Toxicity.............................................. 92 Barbiturates............................................... 92 Benzodiazepines.... Nonbarbiturate, Nonbenzodiazepine Hypnotics.... Chloral Hydrate.... Methaqualone.... Glutethimide..... Ethchloroynol.... Treatment.... Preven tion.... Summary and Conclusions... ".... 93 93 93 94 95 95 96 98 99 6 Residual Daytime Effects of Hypnotics..................... 101 Electrophysiologic Residual Effects............................. 101 Psychomotor Measures of Residual Effects...................... 104.subjective Evaluation of Daytime Performance.................. 111 Hypnotics and Driving... 112 Summary and Conclusions.................................... 113
x CONTENTS 7 Interactions with Ethanol.................................. 115 General Considerations....................................... 116 Barbiturates... 116 Benzodiazepines... 118 Nonbarbiturate, Nonbenzodiazepine Hypnotics................. 122 Chloral Hydrate........................................... 122 Methaqualone............................................. 123 Glutethimide.............................................. 123 Summary and Conclusions.................................... 125 8 Hypnotic Dependence..... 127 Classical Drug Abuse......................................... 128 Dependence in Medical Practice... 129 Dependence on Extremely Large Doses...................... 129 Prolonged Use of Recommended Doses... 130 Incidence and Contributing Factors... 130 Drug Qualities Related to Prolonged Use... 133 Summary and Conclusions.................................... 138 9 Hypnotics and the Elderly................................. 141 Pharmacology in the Elderly... 142 Efficacy Studies.............................................. 145 Toxicity.............................................. 150 Summary and Conclusions.................................... 151 10 Other Pharmacologic Approaches... 153 Over-the-Counter Hypnotics.................................. 153 Compounds Used in OTC Hypnotics....................... 154 Methapyrilene............................................ 154 Scopolamine... 155 Bromides................................................ 156 Efficacy................................................... 156 Federal Regulation......................................... 157
CONTENTS xi L-Tryptophan... 159 Ethanol... 160 Summary and Conclusions.................................... 161 11 Nonpharmacologic Treatment of Insomnia................. 163 Counseling and Psychotherapy................................ 163 Behavioral Therapies... 164 General Considerations... 164 Relaxation Procedures...................................... 166 Conditioning-Derived Therapies... 169 Attributional Therapy...................................... 171 Behavioral Self-Management... "...,... 173 Summary and Conclusions.................................... 173 12 Conclusion: Implications for Medical Practice..., 177 Summary... 177 Approach to the Insomniac Patient... 182 Evaluation... 182 The Decision Whether to Give Hypnotics.................... 183 Acute or Intermittent Insomnia.............................. 184 Chronic Insomnia......................................... 184 When Hypnotics Are Prescribed... 184 References... 187 Index... 217