title: Evaluation of the efficacy and safety of ramelteon in subjects with chronic insomnia.
abstract: OBJECTIVE
  To evaluate efficacy and safety of ramelteon (MT1/MT2-receptor [corrected] agonist) in subjects with chronic primary insomnia.
  
  
  METHODS
  Randomized, multicenter, double-blind, placebo-controlled trial of nightly ramelteon treatment (8 mg or 16 mg) in adults (N=405) with primary chronic insomnia (DSM-IV-TR). Latency to persistent sleep (LPS), TST, sleep efficiency, wake time after sleep onset, and number of awakenings were measured by polysomnography. Subject-reported measures were also assessed.
  
  
  RESULTS
  LPS at Week 1 (primary measure) was significantly shorter with ramelteon 8 mg (32.2 min) or 16 mg (28.9 min) vs placebo (47.9 min; p <0.001). Significant improvements in LPS were maintained at Weeks 3 and 5. TST was significantly longer with both doses of ramelteon at Week 1 (p <0.001) vs placebo. Subject-reported sleep latency was significantly shorter with ramelteon 8 mg at Weeks 1, 3, and 5 (p <0.001) and ramelteon 16 mg at Weeks 1 and 3 (p < or =0.050) vs placebo. Wake time after sleep onset and number of awakenings were not significantly different with ramelteon 8 mg or 16 mg treatment vs placebo. Subjective TST was significantly longer with ramelteon 8 mg at Weeks 1, 3, and 5 (p < or =0.050) and ramelteon 16 mg at Week 1 (p = 0.003) vs placebo. Ramelteon had no clinically meaningful effect on sleep architecture, next-morning psychomotor tasks, alertness, or ability to concentrate. No withdrawal or rebound effects were observed.
  
  
  CONCLUSIONS
  Ramelteon reduced LPS over 5 weeks of treatment in subjects with chronic insomnia, with no clinically meaningful sleep architecture alterations, next-morning residual pharmacologic effects, and no evidence of rebound insomnia or withdrawal. No numerical differences were observed between the 2 doses of ramelteon.
authors.affiliation: Clinilabs Sleep Disorders Institute, New York, NY 10025, USA. gzammit@clinilabs.com
authors.forename: Gary
authors.initials: G
authors.lastname: Zammit
authors.forename: Milton
authors.initials: M
authors.lastname: Erman
authors.forename: Sherry
authors.initials: S
authors.lastname: Wang-Weigand
authors.forename: Stephen
authors.initials: S
authors.lastname: Sainati
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Zhang
authors.forename: Thomas
authors.initials: T
authors.lastname: Roth
mesh_terms: D000328:Adult; D002908:Chronic Disease; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000009:adverse effects* / Q000627:therapeutic use*; D007192:Indenes / Q000008:administration & dosage* / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D017286:Polysomnography / Q000379:methods; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy*; D011795:Surveys and Questionnaires; D016896:Treatment Outcome