title: 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.
  
  
  METHODS
  This study provides Class I evidence that suvorexant improves sleep efficiency over 4 weeks in nonelderly adult patients with primary insomnia.
authors.affiliation: Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA. william.herring@merck.com
authors.forename: W Joseph
authors.initials: WJ
authors.lastname: Herring
authors.forename: Ellen
authors.initials: E
authors.lastname: Snyder
authors.forename: Kerry
authors.initials: K
authors.lastname: Budd
authors.forename: Jill
authors.initials: J
authors.lastname: Hutzelmann
authors.forename: Duane
authors.initials: D
authors.lastname: Snavely
authors.forename: Kenneth
authors.initials: K
authors.lastname: Liu
authors.forename: Christopher
authors.initials: C
authors.lastname: Lines
authors.forename: Thomas
authors.initials: T
authors.lastname: Roth
authors.forename: David
authors.initials: D
authors.lastname: Michelson
mesh_terms: D000293:Adolescent; D000328:Adult; D001381:Azepines / Q000494:pharmacology / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D064446:Orexin Receptors; D017286:Polysomnography; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors*; D012890:Sleep / Q000187:drug effects* / Q000502:physiology; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D001381:Azepines; D006993:Hypnotics and Sedatives; D064446:Orexin Receptors; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; D014230:Triazoles; C551624:suvorexant