Martin B. Scharf

Subjective hypnotic efficacy of trazodone and zolpidem in DSMIII–R primary insomnia

Trazodone is an antidepressant which is used at low doses as a hypnotic. The hypnotic efficacy of trazodone in non‐depressed insomniacs is unknown, especially in comparison to hypnotic medications such as zolpidem. Following a placebo screening week, DSM‐IIIR defined primary insomniacs were randomized into a parallel‐group, double‐blind, 14‐day comparison of trazodone 50 mg, zolpidem 10 mg and placebo. Patients completed daily morning questionnaires and weekly office visits. Self‐reported sleep latencies were compared by the Cox proportional hazards regression technique; self‐reported sleep duration by ANOVA. During treatment Week 1, both drugs produced significantly shorter self‐reported sleep latencies and longer self‐reported sleep durations than placebo. Self‐reported sleep latency was significantly shorter with zolpidem than with trazodone. During Week 2, only the zolpidem group maintained a significantly shorter sleep latency than the placebo group, and self‐reported sleep duration did not vary significantly among groups. The incidence of adverse events was low in all groups. Both trazodone and zolpidem improved self‐reported sleep latency and duration of non‐depressed, primary insomniacs; zolpidem was somewhat more efficacious at the doses studied.

A polysomnography study of eszopiclone in elderly patients with insomnia

ABSTRACT Objective: To evaluate the safety and efficacy of eszopiclone 2 mg in elderly patients (aged 64-86 years) with chronic insomnia. Methods: This was a randomized, double-blind, placebo-controlled 2‐week study. Patients meeting DSM-IV criteria for primary insomnia and screening polysomnography criteria (wakefulness after sleep onset [WASO] ≥ 20 min and latency to persistent sleep ≥ 20 min) were randomized to 2 weeks of nightly treatment with eszopiclone 2 mg (n = 136) or placebo (n = 128). Efficacy was assessed using polysomnography (Nights 1, 2, 13, and 14) and patient reports (Nights 1–14); safety was assessed using adverse events, clinical labs, physical examination, and vital signs. The mean of all efficacy results during the double-blind period was used for the efficacy analysis. Results: Results indicated that eszopiclone was associated with significantly shorter sleep onset, less WASO, higher sleep efficiency, more total sleep time, and greater patient-reported quality and depth of sleep scores than placebo ( p < 0.05 for all) with a trend in patient-reported morning sleepiness ( p = 0.07). Other measures of daytime functioning (ability to function, daytime alertness, and sense of well-being) were not significantly different between the two treatment groups. Among patients who napped, eszopiclone patients reported fewer naps ( p = 0.03) and less cumulative naptime (median: 98 min placebo, 70 min eszopiclone, p = 0.07). Unpleasant taste, dry mouth, somnolence, and dizziness were higher in the eszopiclone group (12.5%, 8.8%, 6.6%, and 6.6%, respectively) than in the placebo group (0%, 1.6%, 5.5%, and 1.6%, respectively). Conclusion: In this study, eszopiclone was well tolerated and produced significant improvements in both polysomnographic and patient-reported measures of sleep maintenance, sleep induction, and sleep duration in elderly patients with chronic primary insomnia.

Efficacy and Tolerability of 14-Day Administration of Zaleplon 5mg and 10mg for the Treatment of Primary Insomnia

AbstractObjective: The efficacy and tolerability of zaleplon 5mg and 10mg, a selective benzodiazepine subtype A receptor agonist, was evaluated during 14-day administration in a double-blind, placebo-controlled design, with triazolam included as an active comparator. Patients and Methods: Polysomnographic data, subjective reports, performance measures, and clinical assessments were made for 132 primary insomniacs, aged 18 to 60 years, during three baseline, 14 drug, and two discontinuation nights. Results: Polysomnographic data indicated that both doses of zaleplon shortened latency to persistent sleep relative to placebo, during early drug administration. By the end of the administration period the difference was no longer statistically significant, principally due to improvement in the placebo group. No effect on total sleep time or measures of awakenings was seen with either zaleplon dose. Triazolam increased total sleep time and reduced latency to persistent sleep compared with placebo on early drug nights, but not at the end of the 2-week administration. In general, subjective data were consistent with polysomnography findings. Clinical evaluations indicated that zaleplon was well tolerated and without residual effects or discontinuation effects. Adverse effects were infrequent, mild and no more common with zaleplon than with placebo. Conclusion: At the doses evaluated, zaleplon appeared to have hypnotic properties consistent with its pharmacokinetic profile, and a low likelihood of undesired effects.

Comparison of the Residual Effects and Efficacy of Short Term Zolpidem, Flurazepam and Placebo in Patients with Chronic Insomnia

SummaryThis multicentre, double-blind, randomised, placebo-controlled, parallel-group study compared the next-day residual effects, hypnotic efficacy and sleep staging effects of zolpidem 10 and 20mg with those of placebo in patients with chronic insomnia. Flurazepam 30mg was used as a positive control for residual effects. Patients completed written and computerised performance tests [Digital Symbol Substitution Test (DSST) was the primary outcome measure], and their sleep was evaluated polysomnographically and subjectively. After treatment with zolpidem for 3 consecutive nights, the change from baseline in number of correct responses on the next-morning DSST or Symbol Copying Test (SCT) was not different to that recorded in placebo-treated patients. Next-day performance was impaired every day after treatment with flurazepam. As measured by objective and subjective criteria, both zolpidem and flurazepam were effective hypnotics. Sleep stages were affected more by flurazepam than by zolpidem. The incidence of treatment-emergent adverse events was approximately the same for zolpidem 10mg, flurazepam and placebo. The 20mg dose of zolpidem (twice the therapeutic dose) was associated with a higher incidence of adverse events. It was concluded that no next-day residual effects are associated with nightly intake (3 nights) of the recommended dose of zolpidem. At this dose, zolpidem was an effective and safe hypnotic.

Outcome evaluation of long-term nasal continuous positive airway pressure therapy in obstructive sleep apnea.

A study was conducted at the Tri-State Sleep Disorders Center of Cincinnati, Ohio, to evaluate both quantitative and qualitative daily function and productivity outcomes of treating obstructive sleep apnea (OSA) with nasal continuous positive airway pressure (NCPAP). This was a prospective outcome study conducted in 316 patients with diagnosed and treated OSA. There were 234 men and 82 women, mean age, 48.79 +/- 0.67 years; weight averaged 250.39 +/- 3.55 pounds; mean pretreatment respiratory disturbance index was 42.9 +/- 1.7 episodes per hour and 2.8 +/- 0.2 episodes per hour with NCPAP treatment. Patients were surveyed by questionnaire, administered on polysomnographic confirmation of OSA and after 6 months of nightly treatment with NCPAP as to their perceptions of their level of daytime functioning and quality of life over the previous 6 months. Main outcome measures included number of incidents of excessive daytime sleepiness; number of headaches on awakening; number of automobile accidents and near-miss automobile accidents; number of days absent from work; number of physician visits; and a series of subjective scales, measuring job productivity, quality of life, general physical and mental condition, short-term memory, and changes in blood pressure. Significant decreases were found in the number of incidents of excessive daytime sleepiness, headaches on awakening, physician visits, days absent from work, and automobile accidents or near misses with NCPAP therapy. Patients also reported subjective increases in productivity, quality of life, physical and mental condition, and short-term memory and reduction in both diastolic and systolic blood pressure. Effective treatment of OSA results in improvement both in preexisting symptoms and in quality of life. Improvement in many of the major problems experienced by patients seeking treatment has important implications for preventive medicine as well as health care cost containment.

EVALUATION OF SLEEP ARCHITECTURE AND CYCLIC ALTERNATING PATTERN RATES IN DEPRESSED INSOMNIAC PATIENTS TREATED WITH NEFAZODONE HYDROCHLORIDE

The standard methods of scoring sleep patterns do not ensure an accurate clinical impression of sleep quality. This is important especially in depressed insomniacs because persistent poor sleep increases the likelihood of recurrent depressive episodes. Changes in cyclic alternating patterns (CAP) in sleep have been shown to reflect corresponding changes in sleep quality. We evaluated the effects of nefazodone on CAP and standard sleep architecture in depressed insomniacs. The study was a single-center, single-blind, 6-week treatment of nefazodone hydrochloride followed by placebo withdrawal in 16 subjects meeting the DSM-IV criteria for depression who had a score of at least 18 on the 17-item Hamilton Depression Rating Scale, with insomnia-related items 4, 5, and 6 having a total score of 3 or greater. A mean daily dose of 339.1 +/- 141.7 mg at endpoint of nefazodone significantly reduced Hamilton Depression Scores from 21.7 +/- 3.0 on baseline to 5.8 +/- 5.3 (P <.05) by the end of the study. Polysomnography showed an improvement in sleep latency and sleep efficiency (P <.05), but no alterations in rapid-eye-movement or slow-wave sleep. Subjective estimates of sleep quality improved throughout the study, but CAP rates did not show a significant improvement. The disparity between CAP rates and sleep quality in depressed insomniacs is discussed.

Safety of long-term zolpidem treatment in patients with insomnia

Abstract Because a substantial number of patients with insomnia take hypnotics for extended periods, maintenance of effectiveness and the effects of withdrawal following long-term use are critical issues. In this multicenter, single-blind study, patients between 18 and 60 years of age (mean, 42 years) received placebo for 4 to 7 nights, followed by 12 weeks of nightly treatment with zolpidem 15 mg, followed by placebo for 1 withdrawal week. If adverse events occurred, the study design allowed for a dose reduction to 10 mg. Efficacy was evaluated subjectively using the Clinical Global Impression scale at the end of the placebo run-in period and at the end of weeks 2, 4, 8, and 12 and placebo week 13. In addition, patients completed self-reports, describing their sleep before each visit. Of the 229 patients who received zolpidem, 155 patients completed all 12 weeks of treatment. Thirty-three patients had their dose decreased from 15 mg to 10 mg at some time during the study. Adverse effects led to withdrawal in only 8% of the patients initially enrolled. The incidence of side effects was considerably higher with the 15-mg dose compared with the 10-mg dose. Despite the prolonged use of higher than currently recommended doses of zolpidem, no evidence of rebound insomnia was reported. In addition, there was no evidence of drug tolerance throughout the 12 weeks of drug administration. In agreement with recommendations of numerous previous studies, the 10-mg dose was found to be safe during the 12-week treatment period.

Comparative effects of prazosin and hydrochlorothiazide on sexual function in hypertensive men

Evidence suggests that there may be differences in the incidence of drug-induced sexual dysfunction among the antihypertensive agents. This study assessed objective and subjective aspects of sexual dysfunction in hypertensive male patients in relation to two antihypertensive agents--prazosin and hydrochlorothiazide. A total of 12 hypertensive patients were evaluated in a crossover study utilizing a sleep laboratory to obtain polysomnographic evaluations of sleep patterns along with changes in nocturnal penile tumescence and buckling pressure. Objectively, no significant changes were observed between the two antihypertensive agents in relation to rapid eye movement-related sleep architecture, serum testosterone levels, or penile blood flow. Decrements in buckling pressure and subjective aspects of sexual dysfunction were greater during hydrochlorothiazide treatment than during prazosin treatment. Both drugs were effective in controlling blood pressure.