title: The effects of ramelteon on respiration during sleep in subjects with moderate to severe chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Individuals with moderate to severe chronic obstructive pulmonary disease (COPD) have poor sleep quality. This study evaluated the effects of ramelteon, an MT(1)/MT(2) melatonin receptor agonist indicated for insomnia treatment on respiration in this population.
  
  
  METHODS
  This double-blind, crossover study enrolled 25 subjects (>or=40 years) with moderate to severe COPD (FEV(1)/FVC <70% and FEV(1) between 50 and 80% of predicted value [moderate], or FEV(1)/FVC <70% and FEV(1) <50% of predicted value [severe]). Subjects received ramelteon 8 mg or placebo for one night 30 min before polysomnographic monitoring, including measurement of oxygen saturation (SaO(2)) and respiratory effort and flow. Subjects crossed to alternate treatment after a 5- to 10-day washout. The primary endpoint was mean SaO(2) for the entire night.
  
  
  RESULTS
  No significant difference in SaO(2) for the entire night was observed with ramelteon vs placebo (92.2% vs 92.5%, P = 0.576). Mean SaO(2) was similar between ramelteon and placebo for each hour of the night, each sleep stage, the number of minutes that SaO(2) was <80% and <90%, and mean apnea-hypopnea index. There was a significant difference in total sleep time (389.0 vs 348.4 min, P = 0.019) and sleep efficiency (81.0 vs 72.6%, P = 0.019), and latency to persistent sleep was shorter (23.1 vs 56.9 min, P = 0.051), with ramelteon vs placebo. All adverse events were mild to moderate; none led to study discontinuation.
  
  
  CONCLUSIONS
  Ramelteon did not produce respiratory depressant effects as measured by oxygenation or abnormal breathing events in subjects with moderate to severe COPD. Ramelteon was well tolerated in this population.
authors.affiliation: Sleep Research and Education, Gaylord Hospital, Wallingford, CT 06492, USA. krygerresearch@hotmail.com
authors.forename: Meir
authors.initials: M
authors.lastname: Kryger
authors.forename: Thomas
authors.initials: T
authors.lastname: Roth
authors.forename: Sherry
authors.initials: S
authors.lastname: Wang-Weigand
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D015897:Comorbidity; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007192:Indenes / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D010092:Oximetry; D017286:Polysomnography; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000453:epidemiology; D044094:Receptors, Melatonin / Q000187:drug effects; D012720:Severity of Illness Index; D012891:Sleep Apnea Syndromes / Q000188:drug therapy; D020181:Sleep Apnea, Obstructive / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D007319:Sleep Initiation and Maintenance Disorders / Q000175:diagnosis / Q000453:epidemiology; D012894:Sleep Stages; D055815:Young Adult
chemical_list: D007192:Indenes; D044094:Receptors, Melatonin; C495910:ramelteon