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Biomedical subjects

T Roth

Publications and source records attributed to T Roth.

At least 37 records · Page 2Linked to original sources

Hypnotics and behavior.

Evaluation of the effects of hypnotics on waking behavior has primarily focused on two issues: (1) how these drugs affect performance the day after a nightly dose; and (2) how they affect memory processes, with special emphasis on anterograde amnesia. In terms of the relations between pharmacologic properties and residual effects, three conclusions can be drawn. First, dose is a major determinant of the presence or absence of morning effects. Every drug studied to date, if given in high enough dose, has produced morning performance decrements. Second, the longer-acting a compound, the more likely it is that a performance decrement will be observed. Finally, some data suggest that behavioral tolerance to the residual effects of hypnotics develops. The observation that benzodiazepines produce amnesia emerged from reports of their clinical use as presurgery medications. Although the initial reports involved intravenous diazepam and were anecdotal in nature, subsequent studies have demonstrated that amnesia is a characteristic of all the benzodiazepines, with the magnitude of the effect being a function of route of administration, dose, and the pharmacokinetics of the particular drug.

Anti-Anxiety Agents

Rebound insomnia: its determinants and significance.

Rebound insomnia is a sleep disturbance that occurs on discontinuation of benzodiazepine hypnotic drugs. It has been reported in both patients and healthy normal subjects and is characterized by increased wakefulness above the person's baseline levels. This article reviews that available information regarding determinants, possible mechanisms, and clinical significance of rebound insomnia. It is concluded that rebound insomnia is a disturbance of one or two nights' duration that primarily follows discontinuation of short- to intermediate-acting benzodiazepines. It occurs at high doses of a given drug, beyond which no additional hypnotic efficacy is evident. There seem to be clear individual differences in the experience of rebound insomnia, but no prospective studies have established which differences predict rebound. It is likely to be avoided by initiating treatment with the lowest effective dose and tapering the dose upon discontinuation.

Anti-Anxiety Agents

Effects of caffeine on alertness.

The alerting effects of caffeine were assessed using a standard physiological measure of daytime sleepiness/alertness, the Multiple Sleep Latency Test (MSLT). Healthy young men (n = 24) were randomly assigned to receive caffeine 250 mg or placebo administered double blind, at 0900 and 1300 hours on each of 2 days. On the 3rd day both groups received placebo to test for conditioning to the alerting effects of caffeine. Each day sleep latency was measured at 1000, 1200, 1400, and 1600 hours and performance (divided attention at 1030 hours and auditory vigilance at 1430 hours) was assessed. Caffeine increased sleep latency (i.e., improved alertness) and auditory vigilance performance compared to placebo. Tolerance to the effects of caffeine on sleep latency developed over the four administrations. On the conditioning test (day 3) the group receiving caffeine the previous two days was more alert and performed better than the placebo group.

Acoustic Stimulation

Subjective and polysomnographic characteristics of patients diagnosed with narcolepsy.

In order to better characterize the subjective and polysomnographic findings in patients with narcolepsy, a follow-up questionnaire was mailed to all patients diagnosed with the disorder at the Henry Ford Hospital Sleep Disorders and Research Center. The questionnaire inquired regarding the present, previous, and change in status for the constellation of narcolepsy symptoms. Memory problems, problems of daytime function, and nocturnal sleep disturbance were included among the questions related to the symptomatic constellation. By definition, all patients were symptomatic of daytime sleepiness and were diagnosed with narcolepsy only if there were two or more rapid eye movement (REM) onsets documented on the polysomnographic evaluation. A high percentage of patients reported nocturnal sleep disturbance, which was one of the symptoms with the latest reported onset. Retrospective comparison of questionnaire responses to the clinical polysomnography revealed significantly more sleep maintenance difficulties in the group of patients reporting this symptom on the questionnaire. Patients with disturbed nocturnal sleep reported taking more naps during the day, although the Multiple Sleep Latency Test (MSLT) failed to show differences in sleep latency. Interestingly, this group of patients was found to have a significantly higher number of sleep onset REM episodes on the MSLT. Finally, the findings are discussed as they compare to studies that required the presence of cataplexy as part of their inclusion criteria.

Adult

Polysomnographic, performance, and personality differences of sleepy and alert normals.

The nocturnal sleep, performance, and personality of healthy, asymptomatic, normal young men, 18 who had unusually short sleep latencies on the Multiple Sleep Latency Test (average latency, less than or equal to 6 min) and 20 with unusually long latencies (average latency, greater than or equal to 16 min) were compared. On the nocturnal sleep recording, sleepy subjects had a shorter sleep latency, less waking time, and overall greater sleep efficiency than alert subjects. During the day, sleepy subjects performed more poorly than alert subjects on divided attention and vigilance performance tasks. The sleepy and alert subjects did not differ appreciably on the Minnesota Multiphasic Personality Inventory and Jenkins Activity measures of personality. On the Institute of Personality and Ability Testing Anxiety Scale, the sleepy subjects showed higher levels of anxiety than the alert subjects. The data were interpreted as indicating that the sleepy subjects had a sleep debt due to chronic sleep restriction.

Adult

The chronic efficacy of midazolam.

The chronic efficacy of midazolam 15.0 mg was studied in 2 male and 10 female subjects. Only subjects with a complaint of sleep latency insomnia which was verified by polysomnography were included in the study. Following a screening and adaptation period, subjects spent 3 consecutive nights in the laboratory during the weeks of the study. Placebo was administered 15 min before lights out on the initial 8 and final 2 nights, and midazolam for the intervening 35 nights. Midazolam significantly reduced sleep latency parameters and significantly increased total sleep time the entire 5 weeks of nightly administration. No within-night rebound insomnia, residual daytime effects, or rebound effects upon discontinuation appeared.

Adult

Individual differences in the sedating effects of ethanol.

Twenty-four healthy, normal-sleeping, males aged 21-35 were screened for basal levels of sleepiness using the Multiple Sleep Latency Test (MSLT). Twelve subjects had basal average daily sleep latencies of less than or equal to 6 min (sleepy) and 12 had latencies of greater than or equal to 16 min (alert) on the MSLT. Subjects consumed either ethanol (0.75 mg/kg) or placebo at 0900-0930 after spending 8 hr time in bed (TIB) the previous night. Sleep latency was measured at 1000, 1200, 1400, and 1600 hr. Divided attention performance and the Stanford Sleepiness Scale (SSS) were assessed at 1100 hr. Breath ethanol concentration (BEC) was determined prior to each latency test. Ethanol decreased average daily sleep latency, divided attention scores and SSS ratings. There were individual differences in the sedating and impairing effects of ethanol, related to subjects' basal level of sleepiness/alertness. The alert subjects exhibited longer sleep latencies and higher performance scores after ethanol administration than the sleepy subjects after placebo. Subjectively the groups had a similar level of sleepiness on placebo and were similarly sedated with ethanol.

Adult

Early onset and accumulation of REM sleep in depression: a study of the phase-advance hypothesis.

Twenty-two depressed subjects who met criteria for major depressive disorder were grouped according to their initial REM latency. Subjects with short (less than or equal to 60 min) initial REM latency were separated from those with normal (greater than 60 min) initial REM latency. Subjects with short initial REM latency were found to have earlier onsets to at least two subsequent REM periods. The number of minutes of REM sleep accumulated were also plotted against elapsed time after sleep onset. The short-latency group accumulated REM sleep earlier than, but at about the same rate as, the normal latency group. These data support the phase-advance hypothesis of REM sleep in depression.

Adult

Psychometric profiles of patient populations with excessive daytime sleepiness.

Patients with narcolepsy have more psychiatric symptoms than normal controls as measured by psychometric tests. However, it is unclear whether these findings are specific to narcolepsy, as some studies have suggested, or related to excessive daytime sleepiness (EDS) or to chronic illness. We compared a group of 56 narcoleptics to age- and sex-matched controls with EDS. A group of 48 individuals with normal sleep architecture was also used as an additional control group. Both the narcoleptic group and the EDS-control group had significantly greater scores on Minnesota Multiphasic Personality Inventory scales but were not different from each other. Our data suggest that the psychopathology associated with narcolepsy is not specific and may be generalized among patients with disorders of excessive sleepiness.

Female

Response to CPAP and UPPP in apnea.

Ninety-two consecutive patients with obstructive sleep apnea syndrome (OSAS) were studied before and six weeks after treatment with either nasal continuous positive airway pressure (CPAP) or uvulopalatopharyngoplasty (UPPP) (n = 46 per group). Assignment of patients to treatment was based on clinical considerations and patient preference. Patients were assessed by nocturnal polysomnography and performance on the Multiple Sleep Latency Test (MSLT) the following day. Before treatment, the CPAP and UPPP groups did not differ in sleep-related respiratory disturbance, oxygenation during sleep, fragmentation of sleep, or the level of excessive daytime sleepiness indicated by the MSLT. Both treatments produced significant improvement on all measures. However, improvement in UPPP patients was significantly less consistent than that of CPAP patients. To the extent that UPPP successfully reversed the respiratory disturbance (i.e., 50% reduction in respiratory events index), sleep continuity and daytime sleepiness were improved to a degree comparable to that of patients treated with CPAP.

Female

Characteristics of chronic insomniacs examined in a multicenter 14-day study of flurazepam and midazolam.

One hundred seven chronic insomniacs (41 men, 66 women; mean age, 37.9 years) with a history of use of benzodiazepines were recruited for a multicenter study testing the relative efficacy of flurazepam 15 mg or 30 mg, midazolam 15 mg, or placebo during a 14-day treatment period. Average duration of the complaint of insomnia was 13.5 years. Most (74%) of the patients met criteria for a diagnosis of persistent psychophysiological sleep disorder for both initiating and maintaining sleep.

Adult

Sleep evaluation in chronic insomniacs during 14-day use of flurazepam and midazolam.

This article contains the sleep results of the efficacy study of flurazepam 30 mg and 15 mg, midazolam 15 mg, and placebo in the 99 chronic insomniacs studied as part of this multicenter study. After a 20-day drug washout, all-night sleep was recorded on 2 baseline nights, on the first 2 treatment nights, on treatment night 7, and on the last 2 nights of the study (nights 13 and 14). To reduce the number of comparisons, electroencephalographic (EEG) sleep latency, EEG wake time, EEG sleep efficiency, post-sleep questionnaire (PSQ) sleep latency, and PSQ total sleep were preselected as the major sleep variables. Between-groups comparisons indicated that, when compared with the placebo control, all drugs improved sleep, but differences were statistically significant only for the first 2 nights, i.e., the early interval. Midazolam was more effective than either dose level of flurazepam on treatment night 1. Within-group analyses indicated that all drug groups showed significantly improved sleep from baseline throughout drug administration, but the placebo group did not significantly improve from baseline by either objective or subjective measures at any of the three time intervals. The sleep of patients taking flurazepam 30 mg did not differ significantly from the sleep of those receiving the 15 mg dose for any of the five major sleep variables at any interval. Objective EEG and subjective PSQ sleep variables showed significant positive correlations.

Adult

Dose effects of temazepam in transient insomnia.

A transient insomnia model, the "first night" effect in the sleep laboratory, was used to assess the dose range for the hypnotic and sleep stage effects of temazepam. 201 healthy, normal subjects (97 men and 104 women), 21 to 49 years old, with no sleep complaints were studied. Each was randomly assigned to receive either placebo, 7.5, 15, or 30 mg temazepam hard gelatin capsules (Restoril) administered double-blind 30 min before bedtime on their first night in the sleep laboratory. Over the 8-h polysomnogram total sleep time and sleep efficiency increased significantly in a linear fashion with increasing doses of temazepam. Sleep tendency was significantly reduced by increasing doses again in a linear manner. Wake time during the sleep period was reduced significantly only by the higher dose. The percentage of stage 1 sleep was reduced and the percentage of stage 2 sleep was increased, each linearly with increasing doses. These data are the first to demonstrate the hypnotic effects of a 7.5 mg dose of temazepam and also support previous studies of 15 and 30 mg temazepam administered to chronic insomniacs. They also illustrate the utility of the "first night" effect as a model of transient insomnia.

Adult

Sleep extension, enhanced alertness and the sedating effects of ethanol.

Twelve, healthy young men (mean age 25.6 years) consumed either ethanol (0.75 g/kg producing a peak breath ethanol concentration, BEC, of 0.060% on average) or placebo at 0900-0930 hr after spending 8 hr time-in-bed (TIB) the previous night and once again after 7 or 8 consecutive nights of 10 hr TIB. Latency to sleep onset (on the Multiple Sleep Latency Test, a standard measure of daytime sleepiness/alertness) was tested at 1000, 1200, 1400 and 1600 hr and divided attention performance was assessed at 1100 hr. Ethanol reduced sleep latency and divided attention performance and the sleep extension improved both sleep latency and divided attention performance. Sleep extension attenuated the sedating effects of ethanol; sleep latency after extending sleep did not differ between placebo and ethanol. While the effects of ethanol on performance still were detectable after sleep extension, the level of performance was at the 8-hr TIB placebo level. BEC peak and decline (determined before each latency test) did not change with the sleep extension. Hence, reduced BECs do not account for the reduction in the disruptive effects of ethanol with sleep extension.

Adult

Characteristics of individuals who do or do not seek treatment for chronic insomnia.

Survey data have shown that a minority of people who complain of insomnia receive medical treatment for this problem. Patients who seek treatment for insomnia at medical clinics and sleep disorders centers are a self-selected group who may not be representative of all individuals with insomnia. Fifty patients presenting to a sleep disorders center with an insomnia complaint were compared to 50 subjects with insomnia recruited through the newspaper for psychopharmacological studies. No differences in sleep parameters were found, but significant differences on psychometric measures and in daytime alertness were present. The implications of these differences are discussed.

Adult