The effects of ramelteon on respiration during sleep in subjects with moderate to severe chronic obstructive pulmonary disease

Sleep Breath. 2009 Mar;13(1):79-84. doi: 10.1007/s11325-008-0196-4. Epub 2008 Jun 27.


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.

Materials and 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.

Conclusion: 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Comorbidity
  • Cross-Over Studies
  • Double-Blind Method
  • Female
  • Humans
  • Indenes / pharmacology
  • Indenes / therapeutic use*
  • Male
  • Oximetry
  • Polysomnography
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / epidemiology
  • Receptors, Melatonin / drug effects
  • Severity of Illness Index
  • Sleep Apnea Syndromes / drug therapy
  • Sleep Apnea, Obstructive / diagnosis
  • Sleep Apnea, Obstructive / drug therapy*
  • Sleep Apnea, Obstructive / epidemiology
  • Sleep Initiation and Maintenance Disorders / diagnosis
  • Sleep Initiation and Maintenance Disorders / epidemiology
  • Sleep Stages
  • Young Adult


  • Indenes
  • Receptors, Melatonin
  • ramelteon