Gail Koshorek

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.

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.

Dose-related effects of estazolam on sleep of patients with insomnia.

The dose range of estazolam for hypnotic effects was studied in seven men and eight women (mean age 30.3 ± 8.6 years) who complained of insomnia and had polysomnographic evidence of disturbed sleep. Patients slept in the laboratory and were monitored using standard polysomnographic techniques. Four consecutive nights in the laboratory with placebo, which served as baseline and screening nights, were followed by five 2-night drug administration periods separated by 5-day drug washout periods spent at home. Each of the patients received a sequence of four doses (0.25, 0.5, 1.0, and 2.0 mg) of estazolam and placebo administered according to a Latin square design and in a double-blind manner. Estazolam significantly increased total sleep time and reduced time awake during sleep in a dose-dependent manner. Sleep latency parameters were reduced systematically with increasing doses of estazolam, but these effects on sleep latency were not statistically significant. Increasing doses of estazolam had systematic and statistically significant effects on sleep stages. Subjective estimations of sleep were consistent with the polysomnographic findings but were not statistically significant.

Hypnotic effects of low doses of quazepam in older insomniacs.

To evaluate the efficacy and safety of reduced doses of the benzodiazepine agonist quazepam in older insomniacs, 30 men and women > 60 years old with chronic insomnia were randomly assigned to receive 0, 7.5, or 15 mg quazepam. After two placebo nights, each subject received the appropriate dose for seven consecutive nights, which was followed by two placebo recovery nights. Both doses increased total sleep time relative to placebo during the early (nights 1 and 2) and late (nights 6 and 7) treatment phases. The low dose reduced sleep latency during the late phase, whereas the high dose reduced sleep latency in both early and late treatment phases. These observed hypnotic effects for both doses did not diminish over the seven nights of repeated administration. There also was a continued hypnotic effect during the two nights of placebo recovery for both doses. Analyses of plasma concentrations of quazepam and its metabolites suggested the continued drug effects on sleep during recovery are due to the metabolite desalkylflurazepam. In the safety evaluation done by means of adverse drug event assessments and postsleep questionnaires, the adverse events reported were minimal and not drug or dose related.

Self-reported levels of sleepiness among subjects with insomnia

Objectives: To determine the prevalence of sleepiness in a cohort of insomnia subjects. We evaluated if differential levels of subjective sleepiness predict systematic differences in the polysomnographic characteristics of these subjects.Background: Insomnia is prevalent among the adult population. While it has been speculated that sleepiness may be an important daytime consequence of insomnia, this has not been demonstrated.Methods: Sixty-two subjects with complaints of insomnia for at least 6 months were polysomnographically evaluated. Subjects were asked to self-report their level of sleepiness based on their experiences for the previous 7 days. Subjects were divided into three groups based on their level of sleepiness. Sleepiness was determined using the excessive daytime sleepiness scale of the Sleep/Wake Activity Inventory (SWAI-EDS).Results: Twenty-two percent of insomnia subjects were found to be sleepy on the EDS scale of the SWAI. The level of sleepiness was also found to predict difficulty initiating sleep both on the nocturnal scale of the SWAI, and on nocturnal polysomnography.Conclusions: This study established a base rate of sleepiness among a cohort of insomnia subjects. It also demonstrated a wide spectrum of sleepiness/alertness among subjects with insomnia. Differential levels of sleepiness were found to predict nocturnal sleep latencies.

Effects of zaleplon or triazolam with or without ethanol on human performance

Objectives and background: Given that non-selective gamma-aminobutyric acid (GABA) agonist hypnotics impair performance and potentiate the disruptive effects of ethanol, this study was done to determine the performance-impairing and ethanol-potentiating effects of zaleplon, a new selective GABA agonist hypnotic.Methods: Eighteen healthy men (12) and women (six), 31.5+/-5.6 years old, were studied. Each underwent six treatments of 2 days in duration, presented in a Latin square design with 2-12 recovery days between. The treatments were: placebo-placebo; placebo-ethanol; triazolam-placebo; triazolam-ethanol; zaleplon-placebo; and zaleplon-ethanol; with triazolam (0.25 mg) or placebo administered at 08:30 h, zaleplon (10 mg) or placebo at 09:00 h, and ethanol (0.75 g/kg) or placebo consumed from 09:30 h. Performance tests were completed each day at 10:30, 12:00 and 14:30 h.Results: Breath ethanol concentration (BrEC), tested 0.5, 2.0, 4.5 and 6 h post consumption, did not differ among treatments and peaked at 0.052%, declining to 0.037, 0.009 and 0.001%. Triazolam with and without ethanol impaired digit symbol substitution, symbol copying, simple and complex reaction times and divided attention performance relative to placebo-placebo treatment. It did so consistently at 10:30 and 12:00 h, and less consistently at 14:30 h. Zaleplon without ethanol impaired only digit symbol substitution and divided attention tracking, and only at 10:30 h. Zaleplon with ethanol impaired most measures at 10:30 and 12:00 h, but not at 14:30 h. Zaleplon without ethanol consistently differed from triazolam without ethanol in the extent of performance impairment. Zaleplon with ethanol began to differ from triazolam with ethanol in performance impairment on the 12:00 and 14:30 h test sessions. Ethanol itself impaired most measures at 10:30 h, fewer at 12:00 h and none at 14:30 h. All active drug treatments increased self-rated sleepiness compared with placebo-placebo. Triazolam without ethanol produced greater self-rated sleepiness than zaleplon without ethanol. The addition of ethanol to both drugs generally produced comparable levels of self-rated sleepiness.Conclusions: In an absolute sense, zaleplon produced less performance impairment and a shorter period of ethanol potentiation than triazolam.