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

Abstract

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.

• Authors: W Joseph Herring, Ellen Snyder, Kerry Budd, Jill Hutzelmann, Duane Snavely, Kenneth Liu, Christopher Lines, Thomas Roth, David Michelson
• Journal: Neurology (Neurology) Vol. 79 Issue 23 Pg. 2265-74 (Dec 04 2012) ISSN: 1526-632X [Electronic] United States
• PMID: 23197752 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Azepines
• Hypnotics and Sedatives
• Orexin Receptors
• Receptors, G-Protein-Coupled
• Receptors, Neuropeptide
• Triazoles
• suvorexant

Topics

• Adolescent
• Adult
• Azepines (pharmacology, therapeutic use)
• Cross-Over Studies
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Humans
• Hypnotics and Sedatives (pharmacology, therapeutic use)
• Male
• Middle Aged
• Orexin Receptors
• Polysomnography
• Receptors, G-Protein-Coupled (antagonists & inhibitors)
• Receptors, Neuropeptide (antagonists & inhibitors)
• Sleep (drug effects, physiology)
• Sleep Initiation and Maintenance Disorders (drug therapy, physiopathology)
• Treatment Outcome
• Triazoles (pharmacology, therapeutic use)