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Biomedical subjects

T Roehrs

Publications and source records attributed to T Roehrs.

At least 19 recordsLinked to original sources

Comparative effects of pravastatin and lovastatin on nighttime sleep and daytime performance.

Pravastatin and lovastatin, two HMG-CoA reductase inhibitors with similar cholesterol-lowering effects, differ in their lipid solubility. The hydrophilic characteristics of pravastatin may explain why the drug has not been detected in cerebrospinal fluid. On the other hand, lovastatin, a lipophilic compound, has been detected in the cerebrospinal fluid. Previous reports have suggested that lovastatin administration may be associated with insomnia, which reflects an action in the central nervous system. The effects of the two drugs on nocturnal sleep and day-time performance in young, healthy men have been assessed in randomized, double-blind, placebo-controlled studies. Computer-based performance tests were administered on two consecutive days before drug administration and at the end of a 3-week active drug or placebo treatment period. Results from both sites were combined for analysis. Neither pravastatin nor lovastatin significantly affected nocturnal sleep or daytime sleepiness in this study population, but lovastatin significantly affected daytime performance. In subjects treated with lovastatin, the results showed that two measures of performance, divided attention (p less than 0.05) and vigilance (p less than 0.01), worsened significantly from baseline as did global performance (p less than 0.01). Performance was not affected in the pravastatin and placebo groups. These results provide preliminary evidence of an adverse effect of lovastatin on daytime performance.

Adolescent

Rebound insomnia and hypnotic self administration.

Twenty-one (three groups of seven), men and women, 25-50 years of age were studied to determine whether or not rebound insomnia would increase the likelihood of self administering a benzodiazepine (triazolam 0.25 mg) hypnotic. The groups compared were patients with insomnia and disturbed sleep, insomnia and normal sleep, and healthy normals. Rebound insomnia, by both subjective and polysomnographic assessment, was induced. The experience of rebound insomnia did not increase the likelihood of self administering a benzodiazepine hypnotic in any of the groups. There were clear group differences in pill self administration with normals rarely and insomnia patients frequently, but not differentially (placebo versus active drug) self administering pills.

Adult

Rebound insomnia in normals and patients with insomnia after abrupt and tapered discontinuation.

Rebound insomnia was studied in subjects, aged 25-50 years, with insomnia complaints and normal sleep, insomnia complaints and disturbed sleep, and normal sleep with no complaints (N = 21, n = 7 per group). Standard sleep recordings were collected on a baseline night and after abrupt discontinuation of 6 nights of 0.50 mg triazolam, tapered discontinuation (3 nights of 0.50 mg, 2 nights of 0.25 mg, and 1 night of 0.125 mg triazolam) and 6 nights of placebo. Significantly disturbed sleep on the discontinuation night compared to the baseline night was found. The relative degree of rebound insomnia was greater in the abrupt condition than in either the tapered or placebo conditions. The tapered condition reduced sleep time by half that of the abrupt condition which was twice the reduction found in the placebo condition. An overall (regardless of group or condition) difference in baseline versus discontinuation sleep was found, suggesting that pill discontinuation itself leads to sleep disturbance. Subjects did not differ in rebound insomnia as a function of pre-existing sleep disturbance.

Adult

Sedating effects of ethanol and time of drinking.

Ethanol (0.5 g/kg) was administered to 12 healthy, normal-sleeping men, aged 21 to 45, at two different times of the day (0900 and 1700 hr). The Multiple Sleep Latency Test (MSLT) was conducted at 1000, 1200, 1400, and 1600 hr in the day drinking condition and at 1800, 2000, 2200, and 2400 hr in the evening drinking condition. On placebo, sleepiness was greater in the daytime testing hours than in the evening, replicating findings on the circadian rhythm of sleepiness/alertness. There was a time of drinking (day versus evening) by ethanol interaction. An ethanol effect on sleep latency was found in the daytime hours, when alertness was relatively low. Ethanol failed to have a significant effect on sleep latency during the evening hours when alertness levels were increasing. Performance on a divided attention task, administered 1 hr postconsumption, was impaired by ethanol consumption, but did not vary as a function of time of drinking (day versus evening). However, at 5 hr postconsumption, mean reaction time on the first 20 min of a 40-min auditory vigilance task was slowed by ethanol to a greater extent after day drinking then after evening drinking.

Adult

Multiple Sleep Latency Test: technical aspects and normal values.

Excessive daytime sleepiness is now recognized as an important medical problem. This paper describes the Multiple Sleep Latency Test (MSLT), a direct, objective method of measuring daytime sleepiness. The standard methodology of the MSLT is outlined, including a description of possible and sources of error in conducting an MSLT. Data regarding the reliability and validity of the MSLT are presented. Finally, normal values are offered, and clinical MSLT results in patients with disorders of excessive daytime sleepiness are interpreted.

Cerebral Cortex

Rebound insomnia: duration of use and individual differences.

This study assessed consistency, duration of use, and individual difference in rebound insomnia. Eleven healthy men, 20-30 years old, with normal sleep by both subjective and polysomnographic criteria, received each of four treatments in a double-blind Latin Square design (triazolam 0.50 mg for 1, 6, and 12 nights and placebo for 12 nights), followed by two placebo discontinuation nights. Triazolam increased sleep compared with placebo without differences in effects between the first and last nights of treatment. On discontinuation following active drug, sleep efficiency was reduced compared with placebo, but duration of administration did not alter the likelihood or intensity of rebound insomnia. Those subjects (5) showing poorer sleep on discontinuation from the 12-night treatment also had poorer sleep in the 1- and 6-night treatment. Subjects with rebound insomnia had poorer baseline sleep and a greater drug effect than did subjects without.

Adult

Alerting effects of caffeine after normal and restricted sleep.

To assess the alerting effects of caffeine after normal and restricted nocturnal sleep, 36 healthy, nonsmoking men, 19 to 35 years old, who reported normal sleep and daytime alertness received 0, 75, or 150 mg caffeine twice daily after 8 and 5 hours in bed the previous night. Sleep restriction reduced average daily sleep latency measured by the Multiple Sleep Latency Test (MSLT) and slowed auditory vigilance reaction time in the latter half of the 40-minute task. Caffeine (75 and 150 mg) increased average daily sleep latency and improved vigilance reaction time. However, sleep restriction did not alter the alerting effects of caffeine. The data show that, unlike ethanol, basal level of sleepiness/alertness does not interact with the effects of caffeine.

Adult

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

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

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

Clinical safety of flurazepam and midazolam during 14-day use in chronic insomniacs.

Data from evening questionnaires, reports of side effects, laboratory findings, and all-night respiratory measurements were collected on the 99 chronic insomniacs examined in this multicenter study. These data were used to compare the clinical safety and desirability of a benzodiazepine hypnotic with a very short half-life, midazolam 15 mg, with a hypnotic with a longer half-life, flurazepam 15 and 30 mg; both compounds were compared with a placebo control. There were 2 prestudy placebo nights followed by 14 consecutive nights of treatment. Of the 107 patients accepted, 99 completed the study. No marked adverse reactions were found in any area for any group. There was no increase in sleep apneas during the treatment period for any group. Results of this study provide additional evidence of the safety of benzodiazepine hypnotics.

Adult

Psychomotor performance in chronic insomniacs during 14-day use of flurazepam and midazolam.

Four skills performance (psychomotor) tasks, including simple and choice reaction time, divided attention, and vigilance, were given to 99 chronic insomniacs to determine whether the use of midazolam 15 mg, or of flurazepam 15 or 30 mg, compared with placebo would produce next-day impairment throughout a 14-day treatment period. Tests were administered during 2 baseline days and on treatment days 1 and 2 (early interval), 7 (middle interval) and 13 and 14 (late interval). Compared with placebo, performance on all four tasks was impaired by flurazepam 30 mg. The deficits associated with flurazepam 15 mg were roughly half the magnitude of those produced by flurazepam 30 mg, but these changes did not reach statistical significance for single response measures at single time intervals. Midazolam showed no consistent pattern of performance effects; however, for divided attention tracking error, there was a significant decrement. The placebo group showed flat performance curves or improved performance as a result of learning (practice effect).

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