Orexin receptor antagonism for treatment of insomnia: A randomized clinical trial of suvorexant

Objective: To assess the utility of orexin receptor antagonism as a novel approach to treating insomnia. Methods: We evaluated suvorexant, an orexin receptor antagonist, for treating patients with primary insomnia in a randomized, double-blind, placebo-controlled, 2-period (4 weeks per period) crossover polysomnography study. Patients received suvorexant (10 mg [n 5 62], 20 mg [n 5 61], 40 mg [n 5 59], or 80 mg [n 5 61]) in one period and placebo (n 5 249) in the other. Polysomnography was performed on night 1 and at the end of week 4 of each period. The coprimary efficacy end points were sleep efficiency on night 1 and end of week 4. Secondary end points were wake after sleep onset and latency to persistent sleep. Results: Suvorexant showed significant (p values ,0.01) dose-related improvements vs placebo on the coprimary end points of sleep efficiency at night 1 and end of week 4. Dose-related effects were also observed for sleep induction (latency to persistent sleep) and maintenance (wake after sleep onset). Suvorexant was generally well tolerated. Conclusions: The data suggest that orexin receptor antagonism offers a novel approach to treating insomnia. Classification of evidence: This study provides Class I evidence that suvorexant improves sleep efficiency over 4 weeks in nonelderly adult patients with primary insomnia.