Guidelines for the multiple sleep latency test (MSLT): a standard measure of sleepiness.
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Humans↗
Biomedical subjects
T Roth
Publications and source records attributed to T Roth.
Dose determinants of rebound insomnia.
A polysomnographic assessment in healthy normal sleepers of possible dose relations for rebound insomnia was conducted. As an additional measure of rebound the study included a direct test of sleep/wake tendency during the night of drug discontinuation. Twelve, healthy men (21-30 years) each received placebo, 0.25 mg and 0.50 mg triazolam for 6 consecutive nights followed by a discontinuation night and 14 nights of recovery at home. The three conditions were presented, double-blind, in a latin square design. On night 6 of drug administration both doses increased total sleep time compared to placebo, but 0.50 mg did not improve sleep beyond 0.25 mg. On drug discontinuation (night 7) wake time over the 8 h recording and sleep latency after an experimental awakening (02.30 h) were increased with 0.50 mg compared to placebo and 0.25 mg. On these measures of rebound 0.25 mg did not differ from placebo. Thus rebound insomnia occurred only at a dose (0.50 mg) which produced no additional hypnotic efficacy in these normal sleepers. Whether tests of sleep/wake tendency make a useful measure of rebound insomnia needs further clarification.
Adult↗
The alerting effects of naps in sleep-deprived subjects.
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Adolescent↗
Chronic hypnotic efficacy of estazolam.
The chronic hypnotic efficacy of estazolam 2.0 mg was studied in five female and seven male subjects. Subjects with a complaint of insomnia verified by polysomnography were included in the study. Following a screening and adaptation period, subjects spent two consecutive nights a week in the laboratory. The protocol for medication was placebo for weeks 1, 2, 9 and 10 and estazolam for weeks 3-8. Estazolam 2.0 mg significantly improved sleep onset and total sleep time for up to six weeks of nightly administration without consistent recovery effects upon discontinuation.
Adult↗
Dose effects of temazepam tablets on sleep.
The dose effects of temazepam tablets (15 and 30 mg) were studied at two sleep centres in 48 volunteers who had objective polysomnographic evidence of sleep onset insomnia. Volunteers slept in the laboratory, retiring at their usual bedtime after taking placebo or temazepam 30 min earlier, and were monitored for 8 h using standard polysomnographic techniques. Acute (nights 5-7) and short term (nights 11-13) temazepam, both 15 and 30 mg, improved the sleep of these volunteers by reducing sleep latency and increasing sleep time compared to the placebo baseline (nights 2-4). Dose differences were found primarily on the measurement of sleep staging, with 30 mg having a greater or more consistent effect than 15 mg. No residual effects were observed on the basis of questionnaires and objective tests of performance and no consistent evidence of disturbed sleep after discontinuing treatment was seen.
Adult↗
Determinants of residual effects of hypnotics.
Studies of hypnotics have generally focused on the effects the drugs have on sleep. It is now clear that they also have effects which can extend beyond the usual sleep period. These residual effects of hypnotics are assessed by studying the effects of these drugs on performance. This paper discusses the issues critical to evaluating studies of the effects of hypnotics on performance. Dose and half-life are important variables in determining the degree to which these daytime effects occur following nighttime use. However, a number of issues have yet to be clarified. Whether residual effects persist with chronic use is not clear. Whether any specific skill may be more or less sensitive to residual effects cannot be determined from the available information. Finally, the degree to which the decrements occur in different populations is not well understood.
Benzodiazepines↗
Efficacy of a reduced triazolam dose in elderly insomniacs.
Elderly persons with insomnia are unique because the cause of their insomnia differs from that of younger people and their metabolism of benzodiazepine hypnotics differs as well. This study used nocturnal polysomnography and daytime sleep/wake tendency measures (Multiple Sleep Latency Test, MSLT) to assess the efficacy and safety of a reduced triazolam dosage (0.125 mg) in elderly subjects with insomnia. After 2 nights and an intervening day of screening each subject received triazolam and placebo for 2 consecutive nights presented in a counter-balanced design. Compared to placebo the reduced triazolam dose induced and maintained sleep thereby increasing total sleep time. Sleep stage distribution and the frequency of apneas and periodic leg movements was not altered. The improved sleep was associated with a restoration of the normal pattern of daytime alertness. The correspondence of this clinical data to known pharmacokinetic data is discussed.
Aged↗
Pharmacological effects of sedative-hypnotics, narcotic analgesics, and alcohol during sleep.
This article briefly reviews the well known effects of sedative-hypnotics, alcohol and narcotics on sleep. These drugs also have respiratory depressant effects, and the limited information about their effects on sleep-related breathing disturbances is reviewed. They exacerbate obstructive sleep apnea syndrome and have moderate to minimal effects on occasional apnea or hypopnea, but do not induce breathing disturbances de novo.
Adult↗
Eligibility requirements in hypnotic trials.
Forty-eight patients complaining of insomnia were studied at two sleep laboratories using an identical protocol to evaluate hypnotic efficacy. All met the screening requirement of a mean sleep latency of 30 min or greater on 3 laboratory nights following an adaptation night. Of these patients 34 still complaining of insomnia were screened a second time 2 to 6 months later. Sixteen of the 34 failed the second screen. Sleep parameters for the 34 on screen 1 compared with screen 2 were the same except for sleep latency (the eligibility criteria), which was significantly shorter. There was no evidence of a systematic difference between laboratories, a change in procedure from screen 1 to 2, or a systematic loss of patients from screen 1 to 2. The data show that the statistical phenomenon of regression toward the mean must be considered in designing hypnotic efficacy studies.
Adult↗
The effects of midazolam and temazepam on sleep and performance when administered in the middle of the night.
A multicenter, double-blind, sleep laboratory and performance study was conducted to evaluate the hypnotic efficacy and residual effects of midazolam (15 mg) and temazepam (30 mg) compared to placebo when administered in the middle of the night. Eighteen volunteers with objectively verified sleep maintenance insomnia received placebo for 3 nights during week 1 (adaptation and screening). During weeks 2, 3, and 4 they received 2 consecutive nights of midazolam, temazepam, and placebo (one treatment per week) in a balanced crossover design. Treatment was administered in the middle of the night (3.5 hours after bedtime). Neither drug reduced the latency to return to sleep after the middle of the night awakening. Both drugs significantly increased total sleep time, reduced wake during sleep, and number of awakenings over 4.5 hours in bed after treatment. In the morning (5 to 6.5 hours postdrug) significant performance decrements and reduced daytime sleep latency (7 hours postdrug) were found with temazepam but not midazolam.
Adult↗
Sleep-wake complaints in patients with sleep-related respiratory disturbances.
The relation of sleep complaint to sleep continuity and respiratory disturbance was studied by comparing 2 series of patients with sleep apnea, one group complaining of insomnia and the other of excessive daytime sleepiness. On polysomnographic evaluation, patients with insomnia complaints had fewer and shorter, primarily central, apneas that had little hypoxemic effects. Patients with excessive sleepiness complaints had more and longer, primarily obstructive, apneas that produced significant hypoxemia. Sleep of the excessively sleepy patients was lighter and longer, whereas that of the patients with insomnia was characterized by more wake time before and after sleep onset. The excessively sleepy patients were objectively sleepy on a test of daytime sleepiness, whereas patients with insomnia were alert.
Adult↗
Evaluation of the effectiveness of uvulopalatopharyngoplasty.
A new surgical procedure to treat obstructive sleep apnea by uvulopalatopharyngoplasty (UPPP) was evaluated in 66 patients, 63 men and 3 women, with objectively documented sleep apnea syndrome. Removal of redundant tissue in the oropharynx (UPPP) significantly improved excessive daytime sleepiness, reduced by half the frequency of apneas and hypoxia occurring during sleep, and improved the quality of sleep. Closer analysis indicated that all 66 patients did not benefit to the same degree. Among patients classified as responders, the frequency of apnea was reduced to a level seen in healthy adults of the same age, measures of sleep approached normal, and excessive daytime sleepiness was eliminated. In nonresponders, frequency of apnea and consequent disruption of sleep was not reduced, but nocturnal hypoxia was improved.
Body Weight↗
Uvulopalatopharyngoplasty. One-year followup.
Uvulopalatopharyngoplasty (UPPP), originally evaluated in 66 patients with objectively documented sleep apnea syndrome, was successful in 33 of the patients as indicated by clinical and polysomnographic improvements. One-year followup polysomnographic evaluations were obtained in 20 of these patients; the remaining 13 were lost to followup. After one year, the patients maintained the improvements seen at the six-week evaluation. Frequency and duration of apnea was significantly reduced from presurgery levels and similar to the six-week results. Oxygenation measures also did not differ from the six-week results, remaining better than presurgery values. Thus, respiration did not disrupt sleep to the degree it had before surgery. Sleep measures were improved compared to presurgery and similar to the six-week data. Body weight remained stable over the entire period.
Female↗
Sustained performance with short evening and morning sleeps.
The effect which early evening sleep may have on overnight and subsequent daytime performance, and the effect which morning sleep may have on daytime performance after overnight sleep deprivation has been studied in six healthy male volunteers. It would appear that relatively short periods of natural and drug induced (brotizolam 0.125 mg) sleep have a beneficial effect on subsequent performance even in the absence of preceding sleep debt. In the event of disturbed sleep in shiftwork an hypnotic may be helpful, and in this context, one which is rapidly eliminated and sustains sleep is appropriate.
Adult↗
Hypnotics and aircrew.
The management of sleep difficulties which arise during air operations must be related, at least initially, to the cause, but the aeromedical specialist is frequently faced with the possible use of hypnotics. There are no simple guidelines, but an understanding of various issues will help toward the effective use of these drugs in those who have to cope with irregularity of rest and carry out skilled work. Some knowledge of the pharmacokinetics of the drugs concerned is useful as persistence of effect and the potential for accumulation with repeated ingestion are important factors, while efficacy in relation to sleep of different durations and at unusual times must also be considered.
Adult↗
Treatment of a 12-hour shift of sleep schedule with benzodiazepines.
Normal sleepers underwent sleep recordings and daytime tests of sleep tendency, performance, and mood while being shifted 180 degrees in their sleep-wake schedule. After two baseline 24-hour periods, subjects postponed sleep until noon. For the next three 24-hour periods, they were in bed from 1200 to 2000 and received triazolam, flurazepam, or placebo at bedtime in parallel groups. Placebo subjects showed significant sleep loss after the shift. Active medication reversed this sleep loss. Despite good sleep, flurazepam subjects appeared most impaired of the three groups on objective assessments of waking function; triazolam subjects were least impaired.
Adult↗
Polysomnographic and MMPI characteristics of patients with insomnia.
This report represents the polysomnographic aspects of sleep and the psychological characteristics 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 might 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. Polysomnographic measures of sleep differed considerably among the diagnostic groups. The groups with medical disorders, respiratory impairment, atypical polysomnographic features, and nocturnal 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Circadian Rhythm↗
Amnesic effects of lormetazepam.
Sixteen healthy men, age 18-35, each received lormetazepam (1.5 mg), flurazepam (30 mg), temazepam (30 mg) and placebo (double-blind in a Latin Square design) 30 min before bedtime for 2 consecutive nights followed by a 12 day washout between conditions. Three hours after drug (2.5 h after bedtime) subjects were awakened and administered a 16-item memory task. Fifteen minutes after the awakening subjects returned to bed, were instructed to go to sleep, and remained in bed for an additional 5.5 h. Immediately after the memory tasks, before returning to bed, subjects recalled almost all of the 16 items when placebo was administered before bedtime. Immediate recall was significantly poorer than placebo after temazepam and flurazepam, but not after lormetazepam. Morning recall was reduced significantly from the immediate nighttime level in each condition; this loss was smallest with placebo. All active drug conditions produced significantly greater amnesia than placebo. This amnesia was smallest after lormetazepam and greatest after temazepam, which differed significantly from each other. All active drugs significantly reduced latency measures of the return to sleep after the 15 min awakening; it was shortest with temazepam and longest with flurazepam. This study showed a relation between the hypnotic and amnesic effects of these drugs which is consistent with their pharmacokinetic properties.
Adolescent↗