Self-reported efficacy and tolerability of ramelteon 8 mg in older adults experiencing severe sleep-onset difficulty.

Background: Ramelteon is a selective MT(1)/MT(2) melatonin receptor agonist indicated for the treatment of insomnia characterized by difficulty with sleep onset.

Objective: The current analysis was conducted to determine the effectiveness of ramelteon 8 mg in reducing the time to fall asleep in older adults with severe baseline sleep-onset difficulties.

Methods: Patients with severe sleep-onset difficulty (defined as subjective sleep latency [sSL] > or =60 minutes) who had received ramelteon 8 mg or placebo were selected from a previously published multicenter outpatient trial of 829 older adults (aged > or =65 years) with primary, chronic insomnia (according to Diagnostic and Statistical Manual of Mental Disorders [Fourth Edition, Text Revision] criteria). Patients received single-blind placebo for 7 days (baseline) before receiving double-blind ramelteon 8 mg or placebo nightly for 5 weeks (35 nights). A 7-day, single-blind, placebo washout period followed. The primary end point was mean sSL for nights 1 through 7 (week 1). The mean changes in sSL from baseline at weeks 3 and 5 were evaluated to assess sustained efficacy. Adverse events (AEs) were collected in this analysis for both the ramelteon 8-mg and placebo groups.

Results: A total of 157 patients from the rameltcon 8-mg group (mean age, 72.7 years; 87 women, 70 men) and 170 patients from the placebo group (mean age, 72.3 years; 111 women, 59 men) met the entry criteria for this post hoc analysis. Ramelteon 8 mg significantly reduced sSL at week 1 compared with placebo (change from baseline, -23.2 vs -7.5 minutes; P = 0.002). This statistically significant improvement was sustained at week 3 (-33.7 vs -19.8 minutes; P = 0.005) and week 5 (-37.4 vs -17.1 minutes; P < 0.001). The incidence of AEs was low. The most commonly reported treatment-emergent AEs were dizziness (ramclteon, 8.9%; placebo, 7.1%), dysgeusia (ramelteon, 7.0%; placebo, 2.9%), myalgia (ramelteon, 6.4%; placebo, 3.5%), and headache (ramelteon, 5.1%; placebo, 5.9%).

Conclusions: In this subset analysis of older adults with severe baseline sleep-onset difficulties, ramelteon 8 mg significantly and persistently reduced subjective reports of time to sleep onset during 5 weeks of nightly treatment. Ramelteon appeared to be an effective and well-tolerated treatment for these older adults with primary, chronic insomnia.