Evaluation of the efficacy and safety of ramelteon in subjects with chronic insomnia.

Abstract

OBJECTIVE:

To evaluate efficacy and safety of ramelteon (MT1/MT2-receptor [corrected] agonist) in subjects with chronic primary insomnia.

METHODS:

Randomized, multicenter, double-blind, placebo-controlled trial of nightly ramelteon treatment (8 mg or 16 mg) in adults (N=405) with primary chronic insomnia (DSM-IV-TR). Latency to persistent sleep (LPS), TST, sleep efficiency, wake time after sleep onset, and number of awakenings were measured by polysomnography. Subject-reported measures were also assessed.

RESULTS:

LPS at Week 1 (primary measure) was significantly shorter with ramelteon 8 mg (32.2 min) or 16 mg (28.9 min) vs placebo (47.9 min; p <0.001). Significant improvements in LPS were maintained at Weeks 3 and 5. TST was significantly longer with both doses of ramelteon at Week 1 (p <0.001) vs placebo. Subject-reported sleep latency was significantly shorter with ramelteon 8 mg at Weeks 1, 3, and 5 (p <0.001) and ramelteon 16 mg at Weeks 1 and 3 (p < or =0.050) vs placebo. Wake time after sleep onset and number of awakenings were not significantly different with ramelteon 8 mg or 16 mg treatment vs placebo. Subjective TST was significantly longer with ramelteon 8 mg at Weeks 1, 3, and 5 (p < or =0.050) and ramelteon 16 mg at Week 1 (p = 0.003) vs placebo. Ramelteon had no clinically meaningful effect on sleep architecture, next-morning psychomotor tasks, alertness, or ability to concentrate. No withdrawal or rebound effects were observed.

CONCLUSIONS:

Ramelteon reduced LPS over 5 weeks of treatment in subjects with chronic insomnia, with no clinically meaningful sleep architecture alterations, next-morning residual pharmacologic effects, and no evidence of rebound insomnia or withdrawal. No numerical differences were observed between the 2 doses of ramelteon.

• Authors: Gary Zammit, Milton Erman, Sherry Wang-Weigand, Stephen Sainati, Jeffrey Zhang, Thomas Roth
• Journal: Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine (J Clin Sleep Med) Vol. 3 Issue 5 Pg. 495-504 (Aug 15 2007) ISSN: 1550-9389 [Print] United States
• PMID: 17803013 (Publication Type: Controlled Clinical Trial, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Hypnotics and Sedatives
• Indenes
• ramelteon

Topics

• Adult
• Chronic Disease
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Female
• Humans
• Hypnotics and Sedatives (adverse effects, therapeutic use)
• Indenes (administration & dosage, adverse effects)
• Male
• Middle Aged
• Polysomnography (methods)
• Sleep Initiation and Maintenance Disorders (drug therapy)
• Surveys and Questionnaires
• Treatment Outcome