title: A double-blind, randomized, placebo-controlled trial of adjunctive ramelteon for the treatment of insomnia and mood stability in patients with euthymic bipolar disorder.
abstract: BACKGROUND
  Abnormalities in circadian rhythms are prominent features of bipolar disorder. Disrupted circadian rhythms are associated with an increased risk of relapse in bipolar disorder. Normalizing the circadian rhythm pattern of bipolar patients may improve their sleep and lead to fewer mood exacerbations. This study evaluated adjunctive ramelteon for the treatment of insomnia and mood stability in euthymic bipolar patients.
  
  
  METHODS
  Participants with euthymic bipolar disorder and sleep disturbances were randomized to receive adjunctive ramelteon or placebo in addition to their regular psychiatric medications for up to 24 weeks or until they experienced a relapse (defined as a depressed or manic event).
  
  
  RESULTS
  83 participants were randomized to receive ramelteon (n=42) or placebo (n=41). Forty participants relapsed (48.2%). Cox regression analyses indicated that participants who received ramelteon (odds ratio 0.48, p=.024) were less likely to relapse. Kaplan Meier curves also indicated longer median survival times in the ramelteon group (Mdn=188 days) versus the placebo group (Mdn=84 days) X2(1)=5.33, p=.02. There were no serious adverse events in this study.
  
  
  CONCLUSIONS
  This was a small study with only 83 participants. The one-week window of confirmed stability is shorter than time intervals used in other studies.
  
  
  CONCLUSIONS
  The present study shows that ramelteon was effective in maintaining stability for individuals with bipolar disorder. Patients treated with ramelteon were approximately half as likely to relapse as patients treated with placebo throughout the 24-week treatment period.
authors.affiliation: Department of Psychiatry, Lehigh Valley Health Network, 1251 S. Cedar Crest Blvd., Suite 202A, Allentown, PA 18103, USA. Edward.norris@lvhn.org
authors.forename: Edward R
authors.initials: ER
authors.lastname: Norris
authors.lastname: Karen Burke
authors.forename: Julia R
authors.initials: JR
authors.lastname: Correll
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Zemanek
authors.forename: Joel
authors.initials: J
authors.lastname: Lerman
authors.forename: Ralph A
authors.initials: RA
authors.lastname: Primelo
authors.forename: Michael W
authors.initials: MW
authors.lastname: Kaufmann
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects; D018692:Antimanic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000494:pharmacology / Q000627:therapeutic use*; D007192:Indenes / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D055502:Secondary Prevention; D012890:Sleep / Q000187:drug effects; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D018692:Antimanic Agents; D006993:Hypnotics and Sedatives; D007192:Indenes; D010919:Placebos; C495910:ramelteon