title: Long-term safety and efficacy of ramelteon in Japanese patients with chronic insomnia.
abstract: OBJECTIVE
  To evaluate the safety of ramelteon, a highly selective MT₁/MT₂ melatonin receptor agonist, during 24 weeks' treatment of Japanese patients with chronic insomnia.
  
  
  METHODS
  In a single-blind, flexible-titration, multicenter study incorporating placebo run-in and run-out periods, 190 adults with chronic insomnia received ramelteon 4 or 8 mg, titrated up to 16 mg if necessary, for 24 weeks. Primary endpoints included adverse events, residual effects, rebound insomnia, withdrawal symptoms, and dependence. Secondary endpoints included subjective sleep latency and total sleep time.
  
  
  RESULTS
  Drug-related adverse events occurred in 11.6% of patients. No clinically important changes occurred in biochemical, hematological or endocrine parameters. There were no signs of next-day residual effect, rebound insomnia, withdrawal symptoms or dependence. Mean subjective sleep latency decreased significantly, and total sleep time increased significantly; both reached a plateau by week 20 and were sustained thereafter (P<0.0001).
  
  
  CONCLUSIONS
  Ramelteon was well tolerated in adult Japanese patients with chronic insomnia and did not cause deterioration of efficacy, residual effects, rebound insomnia, withdrawal symptoms, or dependence after 24 weeks' treatment.
authors.affiliation: Department of Neuropsychiatry, Nihon University School of Medicine, 30-1 Oyaguchi Kamimachi, Itabashi-ku, Tokyo 173-8610, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Uchiyama
authors.forename: Misako
authors.initials: M
authors.lastname: Hamamura
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Kuwano
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagata
authors.forename: Takamasa
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ogawa
authors.forename: Naohisa
authors.initials: N
authors.lastname: Uchimura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D004361:Drug Tolerance; D004703:Endocrine System / Q000187:drug effects; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000009:adverse effects; D007192:Indenes / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010919:Placebos; D044094:Receptors, Melatonin / Q000819:agonists*; D055502:Secondary Prevention; D016037:Single-Blind Method; D012890:Sleep / Q000187:drug effects*; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy*; D013997:Time Factors; D055815:Young Adult
chemical_list: D006993:Hypnotics and Sedatives; D007192:Indenes; D010919:Placebos; D044094:Receptors, Melatonin; C495910:ramelteon