title: Preventive effects of ramelteon on delirium: a randomized placebo-controlled trial.
abstract: OBJECTIVE
  No highly effective interventions to prevent delirium have been identified.
  
  
  OBJECTIVE
  To examine whether ramelteon, a melatonin agonist, is effective for the prevention of delirium.
  
  
  METHODS
  A multicenter, rater-blinded, randomized placebo-controlled trial was performed in intensive care units and regular acute wards of 4 university hospitals and 1 general hospital. Eligible patients were 65 to 89 years old, newly admitted due to serious medical problems, and able to take medicine orally. Patients were excluded from the study if they had an expected stay or life expectancy of less than 48 hours.
  
  
  METHODS
  Sixty-seven patients were randomly assigned using the sealed envelope method to receive ramelteon (8 mg/d; 33 patients) or placebo (34 patients) every night for 7 days.
  
  
  METHODS
  Incidence of delirium, as defined by the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition).
  
  
  RESULTS
  Ramelteon was associated with a lower risk of delirium (3% vs 32%; P = .003), with a relative risk of 0.09 (95% CI, 0.01-0.69). Even after risk factors were controlled for, ramelteon was still associated with a lower incidence of delirium (P = .01; odds ratio, 0.07 [95% CI, 0.008-0.54]). The Kaplan-Meier estimates of time to development of delirium were 6.94 (95% CI, 6.82-7.06) days for ramelteon and 5.74 (5.05-6.42) days for placebo. Comparison by log-rank test showed that the frequency of delirium was significantly lower in patients taking ramelteon than in those taking placebo (χ(2) = 9.83; P = .002).
  
  
  CONCLUSIONS
  Ramelteon administered nightly to elderly patients admitted for acute care may provide protection against delirium. This finding supports a possible pathogenic role of melatonin neurotransmission in delirium.
  
  
  BACKGROUND
  University Hospital Medical Information Network Clinical Trials Registry Identifier: UMIN000005591.
authors.affiliation: Department of Psychiatry, Juntendo University Nerima Hospital, Tokyo, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Hatta
authors.affiliation: Department of Psychiatry, Nippon Medical School Musashikosugi Hospital, Kawasaki, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kishi
authors.affiliation: Department of Psychiatry, Hiroshima City Hospital, Hiroshima, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Wada
authors.affiliation: Department of Psychiatry, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Takeuchi
authors.affiliation: Psychiatric Center Yokohama City University Medical Center, Yokohama, Japan.
authors.forename: Toshinari
authors.initials: T
authors.lastname: Odawara
authors.affiliation: Department of Psychiatry, Juntendo University Nerima Hospital, Tokyo, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Usui
authors.affiliation: Department of Environmental and Preventive Medicine, Kanazawa University Graduate School of Medical Science, Kanazawa, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakamura
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000523:psychology; D003693:Delirium / Q000175:diagnosis / Q000517:prevention & control* / Q000523:psychology; D005260:Female; D006769:Hospitals, General; D006785:Hospitals, University; D006801:Humans; D007192:Indenes / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D012306:Risk; D016037:Single-Blind Method
chemical_list: D007192:Indenes; C495910:ramelteon