The effect of zolpidem on CPAP acclimatization in patients with OSA: a crossover, randomized, double-blinded, placebo-controlled trial

Abstract

STUDY OBJECTIVES: To evaluate the short-term effect of zolpidem on continuous positive airway pressure (CPAP) acclimatization in patients with obstructive sleep apnea compared with placebo. METHODS: This randomized, double-blind, placebo-controlled crossover trial enrolled CPAP-naive patients with obstructive sleep apnea who had an indication for CPAP therapy. Participants were randomly assigned to receive either zolpidem 10 mg or an identical placebo capsule, administered 30 minutes before bedtime for 1 week. In the second week, they crossed over to the alternate treatment. A 24-hour washout period separated the 2 treatment phases. RESULTS: Twenty-eight participants (mean age, 54.5 ± 13.7 years; 57.1% male) completed the study. The mean CPAP usage per night did not differ significantly between zolpidem and placebo (mean difference, 0.18; 95% confidence interval, -0.39 to 0.75). The percentage of nights with CPAP use ≥ 4 hours also showed no significant difference (mean difference, 2.60; 95% confidence interval, -5.65 to 10.87). Treatment sequence did not affect CPAP adherence (P = .87). Subgroup analyses by sex, disease severity, and arousal index revealed no significant impact of zolpidem on adherence. No serious adverse events were reported, and the most common minor adverse event was dizziness (7.14%). CONCLUSIONS: Short-term zolpidem use did not improve CPAP adherence during the acclimatization period. These findings underscore the importance of employing multiple acclimatization strategies rather than relying on routine zolpidem use. Larger-scale studies with extended follow-up are warranted to confirm these results. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Zolpidem on CPAP Acclimatization in OSA; URL: https://clinicaltrials.gov/study/NCT06084130; Identifier: NCT06084130. CITATION: Pisalnoradej P, Banhiran W, Kasemsuk N. The effect of zolpidem on CPAP acclimatization in patients with OSA: a crossover, randomized, double-blinded, placebo-controlled trial. J Clin Sleep Med. 2025;21(11):1831-1837.