Sleep, Benzodiazepines and Performance: Experimental Methodologies and Research Prospects

228 Pages·1984·7.65 MB·English

by  F. Zorick, N. Kribbs, T. Roehrs, T. Roth (auth.), Dr. Ian Hindmarch, Dr. Helmut Ott, Professor Dr. Tom Roth (eds.)

Psychopharmacology Supplementum 1
Sleep, Benzodiazepines
and Performance
Experimental Methodologies and Research Prospects
Editors:
I. Hindmarch H. Ott T. Roth
With 81 Figures
Springer-Verlag
Berlin Heidelberg New York Tokyo 1984
Dr. Ian Hindmarch
Human Psychopharmacology Research Unit, University of Leeds
GB-Leeds, LS2 9JT
Dr. Helmut Ott
Research Laboratories, Section Electrophysiology/Psychometrics, Schering AG
P.O. Box 650311, D-IOOO Berlin 65
Professor Dr. Tom Roth
Sleep Disorders and Research Center, Henry Ford Hospital
Detroit, MI 48202, USA
Library of Congress Cataloging in Publication Data
Main entry under title:
Sleep, benzodiazepines and performance.
(psychopharmacology supplementum; I)
Papers presented at a workshop during the VII. International Congress of Psychiatry in Vienna, 1983.
Bibliography: p. Includes index. I. Insomnia-Chemotherapy-Congresses. 2. Benzodiazepines-Congresses.
3. Insomnia-Research-Congresses. 1. Hindmarch, 1. (Ian), 1944 -. II. Ott, H. (Helmut). III. Roth, T. (Tom).
IV. Series. RCS48.S53 1984 616.8'49 84-5309
ISBN-13: 978-3-642-69661-9 e-ISBN-13: 978-3-642-69659-6
DOl: 10.1007/978-3-642-69659-6
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Preface
The following papers were presented at an International Workshop on experi
mental methodologies and research strategies in sleep, benzodiazepines and per
formance during the VII. International Congress of Psychiatry in Vienna 1983.
Authors were asked to examine and review the methods used and the results
obtained from the various studies within their particular expertise and to provide
guidelines for future strategies in the psychopharmacology of sleep.
It has long been felt by sleep researchers, psychopharmacologists and clini
cians that the effects of drugs on sleep or even sleep itself cannot be evaluated
without reference to the daytime behaviour of the individual. Sleep and daytime
performance are complementary aspects of the same circadian cycle. The modifi
cation of sleep parameters by hypnotic medication must necessarily have an
impact upon daytime behaviour.
The overall change in a patient's daytime behaviour following nocturnal
administration of a benzodiazepine is of importance when considering the toler
ability and safety of the drug in clinical use. Alterations to the integrity of daytime
performance also have consequences for that patient's subsequent sleep and
nocturnal behaviour.
Thus this workshop was conceived as a platform for examining the inter
relationship of sleep, benzodiazepine hypnotics and daytime performance from
pharmacological, psychological, experimental and clinical standpoints. The fol
lowing papers also highlight the complexity of the interaction between sleep,
patient, drug and daytime performance and emphasize the need to approach
problem areas with appropriate research strategies and experimental method
ologies.
I. Hindmarch H. Ott T. Roth
Contents
Sleep and Insomnia
Polysomnographic and MMPI Characteristics of Patients with Insomnia
F. Zorick, N. Kribbs, T. Roehrs and T. Roth ......... 2
Issues in the Diagnosis and Treatment of Insomnia
W. Dement, W. Seidel and M. Carskadon ... 11
Are Poor Sleepers Changed into Good Sleepers by Hypnotic Drugs?
K.Adam. . . . . . . . . . . . . . . . . . . . . . . . 44
Effects of Hypnotics in Insomniacs
Psychological Performance Models as Indicators of the Effects of
Hypnotic Drugs on Sleep
I. Hindmarch . . . . . . . . . . . . . . . . . . . . 58
Sleep Laboratory Study of Lormetazepam in Older Insomniacs
G. W. Vogel .................. . 69
Effects of Two Benzodiazepines on the Speed and Accuracy
of Perceptual-Motor Performance in the Elderly
K. Morgan . . . . . . . . . . . . . . . . . . . . . . . .. 79
Hypnotic Drugs for 1984
I. Oswald. . . . . . . . . . . . . . . . . . . . . . . . .. 84
Pharmacokinetics and Pharmacodynamics of Benzodiazepines
Pharmacodynamics of Benzodiazepines After Single Oral Doses:
Kinetic and Physiochemical Correlates
D. J. Greenblatt, R. M. Arendt and R. I. Shader . . . . . . 92
Lormetazepam - Plasma Concentrations in Volunteers Following
Sublingual and Oral Dosing
D. K. Luscombe. . . . . . . . . . . . . . . . . . . . 98
VIII Contents
Pharmacokinetic and Clinical Studies with a Benzodiazepine
Radioreceptor Assay
R.Dorow .................... . 105
Modern Trends in the Investigation of New Hypnotics in Anaesthesia
A. Doenicke . . . . . . . . . . . . . . . . . . . . . . 119
Are Electroenceophalographic and Psychomotor Measures Sensitive
in Detecting Residual Sequelae of Benzodiazepine Hypnotics?
H. Ott . . . . . . . . . . . . . . . . . . . . . . . . . 133
Differential Effects of Benzodiazepines
Are the Amplitudes of Visual Evoked Potentials Sensitive Indices of
Hangover Effects After Repeated Doses of Benzodiazepines?
J. J. Kulikowski, F. F. McGlone, K. Kranda and H. Ott. . . . 154
Amnesic Effects of Lormetazepam
T. Roehrs, A. McLenaghan, G. Koshorek, F. Zorick and T. Roth 165
The Effects of Benzodiazepines on Short-Term Memory and
Information Processing
Z. Subhan . . . . . . . . . . . . . . . . . . . . 173
Simulated Car Driving as a Useful Technique for Determination
of Residual Effects and Alcohol Interaction After Short- and
Long-Acting Benzodiazepines
H. P. Willumeit, H. Ott and W. Neubert 182
Sleep, Benzodiazepines and Performance: Issues and Comments
1. Hindmarch and H. Ott . . . . . . . . . . . . . . . 194
Author Index 203
Subject Index 217
Sleep and Insomnia
Polysomnographic and MMPI Characteristics
of Patients with Insomnia
F. Zorick, N. Kribbs, T. Roehrs and T. Roth 1
Contents
Abstract 2
1 Introduction 3
2 Methods. 3
2.1 Subjects . 3
2.2 Procedures 3
3 Results 4
3.1 Relative Prevalence 4
3.2 Psychological Characteristics 5
3.3 Polysomnographic Characteristics 7
4 Discussion 8
References. . . . . . . . . . . . 9
Abstract
This report represents the polysomnographic aspects of sleep and the psychological characteris
tics of a large series of patients with insomnia classified according to the diagnostic system of
the Association of Sleep Disorders Centers. The findings for patients in the various diagnostic
categories were compared to those of symptomatic patients with no objective findings. 9 specific
diagnoses were made, but 4 diagnoses accounted for the majority of patients. The 4 most
prevalent were psychophysiological disorders (15 %), psychiatric disorders (17 %), nocturnal
myoclonus and restless legs (18%), and no objective findings (19%).
Patients of a sleep disorders center are a select population and may not be representative of
the general population of patients with insomnia complaints. The psychological characteristics
of the different diagnostic groups were assessed by computing the number of elevations on the
MMPI. Patients with a psychiatric diagnosis exhibited the highest number of MMPI elevations,
as lnight be expected. Patients with nocturnal myoclonus had the lowest number of elevations.
The other groups did not significantly differ from the group with no objective findings. Poly
somnographic measures of sleep differed considerably among the diagnostic groups. The groups
with medical disorders, respiratory impairment, atypical polysomnographic features, and noc
turnal myoclonus had similar short sleep latencies to those of the group with no objective
findings. With longer wake times before sleep and significantly different from patients with no
objective findings were the psychophysiological disorder, psychiatric disorder and drug and
alcohol groups. Patients with a circadian rhythm disturbance had the longest latencies. Time
spent awake after sleep onset was high and significantly different from the no objective findings
group in patients with a psychophysiological disorder, psychiatric disorder, restless legs syn
drome and nocturnal myoclonus diagnosis. The circadian rhythm disturbance group was the
only group without increased wakefulness during sleep. Overall, there were large differences in
the total sleep time of the groups. Finally, quality of sleep as measured by percent stage 1 showed
the greatest number of significant differences compared to patients with no objective findings.
Sleep Disorders and Research Center, Henry Ford Hospital, Detroit, MI 48202, USA
Psychophannacology Supplel11entul11 I
Editors: l. Hindl11arch, H. Ott and T. Roth
© by Springer-Verlag Berlin Heidelberg 1984
Polysomnographic and MMPI Characteristics of Patients with Insomnia 3
Key Words
Diagnostic classification system/Differential diagnosis/ECG /EEG /EM G /EOG /MMPI/N oc
turnal myoclonus/Polysomnographic findings/Psychiatric disorders/Psychological character
istics/Restless legs/Sleep disorders centers.
1 Introduction
The importance of the differential diagnosis of insomnia complaints has become
very evident based on the accumulated experience of clinicians at sleep disorders
centers. To address the problem of differential diagnosis of insomnia the Associ
ation of Sleep Disorders Centers published the first diagnostic classification sys
tem for disorders of initiating and maintaining sleep (Association of Sleep
Disorders Centers 1979). In an earlier report we applied the association's
classification system to a series of patients with insomnia (Zorick et al. 1981). We
reported polysomnographic findings for different diagnostic groups based on
comparisons to normal volunteers. However, there was a small number of pa
tients in each of the diagnostic categories making it important to replicate the
previous findings. Additionally, in that series we found a group of symptomatic
patients (no objective findings) who had normal sleep; they did not differ in
polysomnographic aspects of sleep from the asymptomatic controls. These symp
tomatic, but normal sleepers, are a more appropriate comparison group.
This report presents the polysomnographic aspects of sleep and psychological
characteristics of <lit "large series of patients with insomnia who were classified
according to the association's diagnostic system. Findings for patients in the
various diagnostic categories were compared to those of symptomatic patients
with no objective findings.
2 Methods
2.1 SUbjects
The subjects of this report are 199 patients, 96 women and 103 men, at the Henry
Ford Hospital Disorders Center who were evaluated for their complaint of diffi
culty initiating and maintaining sleep (DIMS). Most were referred by a physician
and all patients had had their sleep problem for a minimum of six months.
2.2 Procedures
Before the initial clinic visit each patient completed a questionnaire detailing the
history and symptoms of their sleep complaint. Each also provided a two-week
sleep diary of their usual sleep habits. During the clinical interview the sleep
history was reviewed, a medical and psychiatric history taken, and a physical and
mental status examination was given. The Cornell Medical Index and the Minne
sota Multiphasic Personality Inventory (MMPI) were also completed.
Seven days before undergoing a polysomnogram all sedative medications
were discontinued. Use of other medications, including diuretics, antihyperten-
4 F. Zorick et al.
sives, digitalis, and tricyclic antidepressants, within seven days of the polysomno
gram were allowed if clinically indicated. 28 % of patients in this series had used
one of these medications prior to the polysomnogram.
At least one all-night polysomnographic evaluation was obtained from each
patient. The polysomnogram included the standard central (C3) and occipital
(Oz) electroencephalograms (EEGs), electrooculogram (EOG), submental elec
tromyogram (EMG), and electrocardiogram (ECG) recorded with a V5 lead. In
addition airflow was monitored with oral and nasal thermistors and leg move
ments with electrodes placed over the right and left tibialis muscles. All recordings
were scored for sleep stages according to the standards of Rechtschaffen and
Kales (1968). Respiration recordings and tibialis EMG recordings were evaluated
by a clinical polysomnographer (Guilleminault 1982).
Each patient then received a specific diagnosis derived from the Association
of Sleep Disorders Centers Diagnostic Classification of Sleep Disorders (Associa
tion of Sleep Disorders Centers 1979). This diagnosis, based on the results of the
entire clinical evaluation including the interview, questionnaires, and nocturnal
polysomnogram, was the consensus diagnosis of three clinical polysomno
graphers. Each patient in this series received a single diagnosis that accounted for
the full spectrum of signs and symptoms observed. Comparisons among diagnos
tic groups were made using analyses of variance and post hoc t-tests and the chi
square where data were nonparametric.
3 Results
3.1 Relative Prevalence
The prevalence of different diagnoses at this center is presented in Table 1. Nine
specific diagnoses were made, but four diagnoses accounted for the majority of
patients. The four most prevalent were psychophysiological disorders (15%),
psychiatric disorders (17 %), nocturnal myoclonus and restless legs (18 %), or no
objective findings (19 %). Within each diagnostic group the distribution of men
and women was even except for the drug or alcohol use, respiratory impairment,
and nocturnal myoclonus groups which were about two-thirds male.
Table 1. Relative prevalence of diagnoses
Diagnoses n % of Total % Male
Psychophysiological disorder 29 15 48
Psychiatric disorder 35 17 50
Drug or alcohol use 13 7 69
Sleep-related respiratory impairment 15 8 73
Nocturnal myoclonus and restless legs syndrome 36 18 58
Medical disorder 12 6 50
Circadian rhythm disturbance 11 5 64
No objective findings 38 19 42
Atypical polysomnographic features 10 5 40
Total 199