Gender Differences in the Efficacy and Safety of Chronic Nightly Zolpidem

Abstract

Study objectives: Studies have shown pharmacokinetic differences for hypnotics in women compared to men, but few studies have assessed either short-or long-term differences in efficacy and safety.

Methods: To evaluate gender differences in the efficacy and safety of chronic nightly zolpidem (10 mg), we did a post hoc assessment of a large clinical trial. In the trial, participants with primary insomnia (n = 89), ages 23-70, meeting DSM-IV-TR criteria for primary insomnia were randomized, double blind, to nightly zolpidem, 10 mg (n = 47) or placebo (n = 42) 30 minutes before bedtime nightly for 12 months. Polysomnographic sleep on 2 nights in months 1 and 8 and likelihood of next-day sleepiness, rebound insomnia, and dose escalation were evaluated in months 1, 4, and 12.

Results: Relative to placebo, zolpidem significantly increased sleep efficiency and reduced sleep latency and wake after sleep onset assessed at months 1 and 8, with no differences in efficacy between women and men and no diminution of efficacy over months. On a next-day multiple sleep latency test (MSLT), no residual sedation was observed for either women or men. No rebound insomnia or dose escalation was seen with no gender differences in either.

Conclusions: In adults with primary insomnia, nightly zolpidem administration showed no gender differences in acute or chronic efficacy or in next-day sleepiness. Zolpidem remained efficacious and safe across 12 months. CLINCIAL TRIALS REGISTRATION: ClinicalTrials.gov Identifier: NCT01006525; Trial Name: Safety and Efficacy of Chronic Hypnotic Use; http://clinicaltrials.gov/ct2/show/NCT01006525.

Keywords: gender differences; primary insomnia; zolpidem.

Figure 1

(A) Total number of placebo capsules chosen by women and men in the placebo group in months 1, 4, and 12. Total possible choices each month 15 (3 on each of 5 nights). Number chosen increased in months 4 and 12 relative to month 1 (Group × Month interaction p < 0.05) in the placebo group with no gender difference. (B) Total number of placebo and zolpidem capsules chosen by men and women in the zolpidem group in months 1, 4, and 12. After choosing placebo or zolpidem on a given night a total of 3 capsules could be taken on each of 5 nights. No significant month or gender differences were found in the zolpidem group. Pbo, placebo; Zol, zolpidem.