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.

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.

• Authors: Meir Kryger, Thomas Roth, Sherry Wang-Weigand, Jeffrey Zhang
• Journal: Sleep & breathing = Schlaf & Atmung (Sleep Breath) Vol. 13 Issue 1 Pg. 79-84 (Mar 2009) ISSN: 1522-1709 [Electronic] Germany
• PMID: 18584227 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Indenes
• Receptors, Melatonin
• ramelteon

Topics

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