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 = 62], 20 mg [n = 61], 40 mg [n = 59], or 80 mg [n = 61]) in one period and placebo (n = 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.