Effects of ramelteon 8 mg on objective sleep latency in adults with chronic insomnia on nights 1 and 2: pooled analysis

Objective: Ramelteon is an MT1/MT2 melatonin receptor agonist indicated for the treatment of insomnia characterized by difficulty with sleep onset. In previous clinical studies, ramelteon reduced latency to persistent sleep (LPS) in subjects with chronic insomnia. The goal of the current analysis was to determine the average reduction in LPS and overall adverse event profile for subjects taking ramelteon 8 mg.Research design and methods: This pooled analysis examined four randomized, double-blind, placebo-controlled clinical trials of ramelteon in subjects with chronic insomnia. The analysis included adults (age 18–83 years) with chronic insomnia who took ramelteon 8 mg or placebo. The primary endpoint of each trial was mean LPS, measured by polysomnography (PSG) on nights 1 and 2. Adverse events were collected for all subjects for the duration of each trial.Results: Efficacy data were available for 566 subjects who took ramelteon 8 mg (mean age 46.7 years) and 556 subjects who took placebo (mean age 47.8 years). Mean LPS at baseline was 66.6 min for the placebo group and 66.9 min for the ramelteon group. At nights 1 and 2, mean LPS for the ramelteon 8 mg group (30.2 min) was significantly less than the mean LPS for the placebo group (43.3 min). The least squares mean difference from placebo was –13.1 min (p < 0.001). Headache (8.9% ramelteon 8 mg, 8.8% placebo) and somnolence (3.5% ramelteon 8 mg, 0.7% placebo) were the most common adverse events.Conclusions: Ramelteon 8 mg, on average, reduced LPS by approximately 13 min more than placebo on nights 1 and 2 of treatment in adults with chronic insomnia. Ramelteon was well tolerated with a low incidence of adverse events. This mean reduction in LPS versus placebo is similar to what has been reported for other classes of insomnia medications. However, these results reflect nights 1 and 2 of treatment and may not be representative of longer treatments.