Timothy Roehrs

Sleep disturbance in menopause

Objective:To determine the sources of sleep complaints in peri- and postmenopausal women reporting disturbed sleep. Design:A total of 102 women, ages 44 to 56 years, who reported disturbed sleep were recruited through newspaper advertisements. They were assessed with the Pittsburgh Sleep Quality Index and the Hamilton Anxiety and Depression Rating Scales. Complete polysomnography was performed in a controlled laboratory setting. Results were analyzed by multiple regression. Results:Fifty-three percent of the women had apnea, restless legs, or both. The best predictors of objective sleep quality (laboratory sleep efficiency) were apneas, periodic limb movements, and arousals (R2 = 0.44, P < 0.0001). The best predictors of subjective sleep quality (Pittsburgh Sleep Quality Index global score) were the Hamilton anxiety score and the number of hot flashes in the first half of the night (R2 = 0.19, P < 0.001). Conclusions:Primary sleep disorders (apnea and restless legs syndrome) are common in this population. Amelioration of hot flashes may reduce some complaints of poor sleep but will not necessarily alleviate underlying primary sleep disorders. Because these can result in significant morbidity and mortality, they require careful attention in peri- and postmenopausal women.

Tolerance to daytime sedative effects of H1 antihistamines.

Sedation is the principal side effect of firstgeneration H1 antihistamines, and recent studies have suggested that this side effect should limit the clinical application of these drugs. The sedative effect also underlies the use of these first-generation drugs as nonprescriptive remedies for insomnia. In both cases, the potential for tolerance to the sedative effect of these drugs is an important issue for which there are few objective data. In the study reported here, 15 healthy men age 18 to 50 years received either diphenhydramine 50 mg or placebo twice a day for 4 days in a randomized, double-blind, crossover trial design. Dependent measures included objective and subjective assessments of sleepiness and computer-based tests of psychomotor performance. Both objective and subjective measures of sleepiness showed significantly higher levels on day 1 for diphenhydramine compared to placebo. By day 4, however, levels of sleepiness on diphenhydramine were indistinguishable from placebo. Similarly, diphenhydramine produced significant impairment of performance that was completely reversed by day 4. These data provide the first objective confirmation that tolerance develops to the sedative effect of a prototypical first-generation H1 antihistamine, diphenhydramine. On this dosing regimen, tolerance was complete by the end of 3 days of administration. While other antihistamines and dosing regimens may differ, these results suggest that tolerance to the sedation produced by these drugs develops with remarkable rapidity.

Ethanol as a Hypnotic in Insomniacs: Self Administration and Effects on Sleep and Mood

The purpose of this study was to assess the effects of low ethanol doses on sleep and mood and to assess its reinforcing effects used as a hypnotic. Twenty healthy adults, aged 21–45 yrs, all moderate social drinkers, were studied: eleven subjects had insomnia and nine were normal sleepers, as documented by clinical polysomnography. On two sampling nights each, ethanol (0.5 g/kg) or placebo was administered before sleep in color-coded cups presented in three doses (0.2, 0.2, and 0.1 g/kg) separated by 15 min. On three subsequent nights subjects chose their preferred pre-sleep beverage (0.2 g/kg ethanol or placebo) based on cup color and were given an opportunity for 3 additional refills (0.2 g/kg each) of the chosen beverage at 15 min intervals, yielding a total possible dose of 0.8 g/kg. Insomniacs chose ethanol 67% of nights and normals 22%. Insomniacs chose significantly more ethanol refills than normals for an average nightly dose of 0.45 g/kg and normals took significantly more placebo refills. On the sampling nights 0.5 g/kg ethanol reduced REM sleep for both groups for the 8-hr sleep period and in insomniacs increased stage 3-4 sleep and reduced stage 1 sleep during the first half of the night to the level seen in the normals. Other sleep variables were not altered in either group or halves of the night. Pre-sleep improvements in the Profile of Mood States tension and concentration factors were also associated with ethanol administration. Thus, acutely, both sleep and mood effects appear to be associated with the reinforcing effects of ethanol as a hypnotic for insomniacs.

Effects of REM sleep and ambient temperature on hot flash-induced sleep disturbance.

Objective: To determine whether hot flashes produce sleep disturbance in postmenopausal women. Design: This study was performed in a university medical center laboratory with 18 postmenopausal women with hot flashes, six with no hot flashes, and 12 cycling women, all healthy and medication free. Polysomnography, skin and rectal temperatures, and skin conductance to detect hot flashes were recorded for four nights. Nights 2, 3, and 4 were run at 30°C, 23°C, and 18°C in randomized order. Results: During the first half of the night, the women with hot flashes had significantly more arousals and awakenings than the other two groups and the 18°C ambient temperature significantly reduced the number of hot flashes, from 2.2 ± 0.4 to 1.5 ± 0.4. These effects did not occur in the second half of the night. In the first half of the night, most hot flashes preceded arousals and awakenings. In the second half, this pattern was reversed. Conclusions: In the second half of the night, rapid eye movement sleep suppresses hot flashes and associated arousals and awakenings. This may explain previous discrepancies between self-reported and laboratory-reported data in postmenopausal women with hot flashes.

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 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.

The dose effects of zolpidem on the sleep of healthy normals.

This study determined the dose effects of zolpidem in 12 healthy males with normal sleep patterns. Subjects spent 7 weeks, 3 consecutive nights per week, in the laboratory and had a 4-night washout between treatments. The first week was a screening and adaptation week. Then subjects received zolpidem (2.5, 5.0, 7.5, 10.0, or 20.0 mg) or placebo on the first two nights for each of the next 6 consecutive weeks. Treatments were organized in a Latin square design and administered in a double-blind fashion. On the third night of each treatment, subjects always received placebo. The 5.0 mg and larger doses of zolpidem significantly decreased latency to persistent sleep and wake before sleep. Sleep maintenance measures were not affected by zolpidem. The 7.5 mg and higher doses of zolpidem significantly increased total sleep time. The only significant sleep stage effect was a decrease in percent of rapid eye movement sleep at only the 20 mg dose. No consistent discontinuation effects were found. Zolpidem was hypnotically active at doses as low as 5.0 and 7.5 mg, and sleep stage effects occurred only at the 20 mg dose, thus separating the dose range of hypnotic and sleep stage effects.

Substance use for insomnia in Metropolitan Detroit

OBJECTIVE People with insomnia are not typically treated medically for their insomnia. Studies have reported approximately 30% of insomniacs self-medicate with alcohol or over-the-counter (OTC) medications. This study was done to identify determinants and risks of different insomnia therapeutics. METHODS A random-digit-dial, computer-assisted survey of a representative sample of adults in Metropolitan Detroit, aged 18-65 years, is being conducted. A sample of all respondents over an 18-month period was collected (n=1324) with a 68% response rate. Exclusive past-year use of alcohol for sleep was reported by 10% (n=132), prescription medications by 8% (n=108), and OTC medications by 10% (n=135). Five percent used both alcohol and sleep medications. The three exclusive-use groups formed the comparison groups of the study. RESULTS The prescription drug group used medications for more consecutive nights and for more total nights than the alcohol and OTC users. Alcohol users were predominantly male, while OTC and prescription drug users were predominantly female. Alcohol users were more likely to be single than the others, and prescription drug users were older than the others. Prescription drug users had more severe insomnia and had greater disability, neuroticism, and daytime fatigue than the others. In contrast, the alcohol users had greater daytime sleepiness than the others. CONCLUSIONS In Metropolitan Detroit, insomniacs receiving medical treatment have more severe insomnia and greater disability than those who self-treat. However, while the insomnia of those self-treating is less severe, it is still associated with some risks.

Pain Sensitivity and Recovery From Mild Chronic Sleep Loss

STUDY OBJECTIVES To determine whether an extended bedtime in sleepy and otherwise healthy volunteers would increase alertness and thereby also reduce pain sensitivity. SETTING Outpatient with sleep laboratory assessments. PARTICIPANTS AND INTERVENTIONS Healthy volunteers (n = 18), defined as having an average daily sleep latency on the Multiple Sleep Latency Test (MSLT) < 8 min, were randomized to 4 nights of extended bedtime (10 hr) (EXT) or 4 nights of their diary-reported habitual bedtimes (HAB). On day 1 and day 4 they received a standard MSLT (10:00, 12:00, 14:00, and 16:00 hr) and finger withdrawal latency pain testing to a radiant heat stimulus (10:30 and 14:30 hr). RESULTS During the four experimental nights the EXT group slept 1.8 hr per night more than the HAB group and average daily sleep latency on the MSLT increased in the EXT group, but not the HAB group. Similarly, finger withdrawal latency was increased (pain sensitivity was reduced) in the EXT group but not the HAB group. The nightly increase in sleep time during the four experimental nights was correlated with the improvement in MSLT, which in turn was correlated with reduced pain sensitivity. CONCLUSIONS These are the first data to show that an extended bedtime in mildly sleepy healthy adults, which resulted in increased sleep time and reduced sleepiness, reduces pain sensitivity.

Caffeine reversal of ethanol effects on the multiple sleep latency test, memory, and psychomotor performance.

Caffeine has been shown to reverse some of the performance-impairing effects of ethanol. However, it is not known whether this antagonistic effect of caffeine is mediated by a reduction in sleepiness. The present study assessed physiological alertness/sleepiness, memory, and psychomotor performance following the administration of placebo, ethanol, and caffeine+ethanol combinations. A total of 13 healthy individuals (21–35 years old) underwent four conditions presented in a Latin Square Design: placebo–placebo, ethanol (0.5 g/kg)–placebo, ethanol (0.5 g/kg)–caffeine 150 mg, and ethanol (0.5 g/kg)–caffeine 300-mg. The Multiple Sleep Latency Test (MSLT), psychomotor performance battery, memory test, and mood/sleepiness questionnaires were administered following each condition. The peak breadth ethanol concentration (BrEC) was 0.043±0.0197% and did not differ among the three caffeine treatments. As expected, ethanol reduced mean latency on the MSLT. The lowest caffeine dose reversed this effect and the highest dose increased mean latency (greater alertness) significantly beyond placebo levels. Ethanol also impaired psychomotor performance and memory. The 300-mg caffeine dose restored performance and memory measures to placebo levels. Although visual analog ratings of dizziness were increased by ethanol, they were not diminished by either caffeine dose. In conclusion, Low-dose caffeine prevented the sleepiness and performance impairment associated with a moderate dose of ethanol. Thus, caffeine, similar to other stimulants, can reverse the physiologically sedating effects of ethanol, although other negative effects remain.

MSLT in primary insomnia: Stability and relation to nocturnal sleep

STUDY OBJECTIVES To assess the stability of the multiple sleep latency test (MSLT) in primary insomnia and its relation to total sleep time. DESIGN Randomized, double-blind, placebo controlled, clinical trial. SETTING Outpatient with sleep laboratory assessments in months 1 and 8 of treatment. PARTICIPANTS Ninety-five primary insomniacs, 32-64 years old and 55 age- and sex-matched general population-based, representative controls. INTERVENTIONS After a screening nocturnal polysomnograms (NPSG) and MSLT the following day, participants with primary insomnia were randomized to take zolpidem 10 mg (n = 50) or placebo (n = 45) nightly for 12 months. During months 1 and 8, while taking their prescribed treatments, NPSGs and MSLTs the following day were conducted. A population-based sample served as controls and received a single NPSG followed by MSLT. RESULTS Mean daily sleep latency on the screening MSLT of insomniacs was normally distributed across the full range of MSLT scores and significantly higher than those of a population-based representative control sample (P < 0.006). The insomniacs with the highest screening MSLTs had the shortest screening total sleep times (P < 0.05). The MSLTs of insomniacs during treatment in study month 1 were correlated (r = 0.44, P < 0.001) with their month 8 MSLT. The mean MSLT score of the zolpidem group did not differ from that of the placebo group, and the stability within treatment groups also did not differ. CONCLUSIONS These data support the hypothesis that some insomniacs show a reliable disorder of hyperarousal with increased wake drive both at night and during the day.