Ramelteon 8 mg/d versus placebo in patients with chronic insomnia: post hoc analysis of a 5-week trial using 50% or greater reduction in latency to persistent sleep as a measure of treatment effect.

Abstract

BACKGROUND:

Ramelteon is a selective MT1/MT2 melatonin receptor agonist approved by the US Food and Drug Administration for insomnia treatment.

OBJECTIVE:

The aim of this post hoc analysis was to compare the efficacy and tolerability of ramelteon 8 mg/d versus placebo in adults with chronic insomnia.

METHODS:

This study analyzed data from a previously published 5-week, randomized, double-blind, placebo-controlled study. Patients aged 18 to 64 years with chronic insomnia were randomly assigned to receive ramelteon 8 or 16 mg/d or placebo QD for 5 weeks. Sleep parameters were evaluated using polysomnography at weeks 1, 3, 5, and 6 (placebo runout). In this post hoc analysis, patients who received ramelteon 8 mg (approved dose) or placebo in the original study were evaluated using a primary end point of a=50% reduction from baseline in latency to persistent sleep (LPS).

RESULTS:

A total of 270 adults (ramelteon 8 mg, 139 patients, mean age, 38.0 years; placebo, 131 patients, mean age, 39.7 years) met the criteria for inclusion in this analysis. One patient from the original study (ramelteon 8-mg/d group) was excluded from the post hoc analysis based on a lack of evaluable LPS data. Ramelteon was associated with significantly greater proportions of patients who achieved a > or = 50% reduction in LPS compared with placebo at weeks 1 (63.0% vs 39.7%; P < 0.001), 3 (63.0% vs 41.2%; P < 0.001), and 5 (65.9% vs 48.9%; P < 0.005). No rebound insomnia or withdrawal effects were observed. Headache (19.4% and 18.3%), fatigue (9.4% and 2.3%), and somnolence (7.9% and 1.5%) were the most common adverse events.

CONCLUSIONS:

In this post hoc analysis of data from patients with chronic insomnia, a significantly greater percentage experienced a > or = 50% reduction in LPS with ramelteon 8 mg/d versus placebo. This improvement was evident at week 1 and was sustained through 5 weeks of treatment. Ramelteon 8 mg was well tolerated in this study, with no evidence of withdrawal or rebound insomnia.

• Authors: Louis Mini, Sherry Wang-Weigand, Jeff Zhang
• Journal: Clinical therapeutics (Clin Ther) Vol. 30 Issue 7 Pg. 1316-23 (Jul 2008) ISSN: 0149-2918 [Print] United States
• PMID: 18691991 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Indenes
• Receptor, Melatonin, MT1
• Receptor, Melatonin, MT2
• ramelteon

Topics

• Adult
• Chronic Disease
• Female
• Humans
• Indenes (administration & dosage, adverse effects, therapeutic use)
• Male
• Randomized Controlled Trials as Topic
• Receptor, Melatonin, MT1 (agonists)
• Receptor, Melatonin, MT2 (agonists)
• Sleep (drug effects)
• Sleep Initiation and Maintenance Disorders (drug therapy, physiopathology)
• Substance Withdrawal Syndrome (etiology)
• Time Factors