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 shortor 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 Citation: Roehrs TA, Roth T. Gender differences in the efficacy and safety of chronic nightly zolpidem. J Clin Sleep Med 2016;12(3):319-325. I NTRO DUCTI O NGender-related pharmacokinetic differences in zolpidem plasma concentration have been reported, with plasma concentrations in women being higher and clearance slower than in men. Men metabolized the 10 mg standard formulation of zolpidem at approximately double the rate of women.1,2 The peak concentration of the sublingual formulation of zolpidem was 45% higher in women than men.3 Some studies have shown that these pharmacokinetic differences are associated with safety differences. At 5 h post daytime zolpidem administration and testing, poorer automobile driving was found 3 and in the morning 4 h after middle of the night zolpidem administration, poorer automobile driving was shown in women than men. 4 It should be noted that these pharmacokinetic studies were done in healthy volunteers and not patients with insomnia for whom this medication is indicated.Many insomnia patients use prescription hypnotics chronically, with over half taking hypnotics longer than 4 weeks, likely due to their chronic and frequent symptomatology. [5][6][7][8] Given this evidence of long-term hypnotic use in insomnia, it is also of interest to assess long-term gender differences in the efficacy and safety of zolpidem. Contro...

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