Effects of ramelteon on patient-reported sleep latency in older adults with chronic insomnia

Background and purpose: To assess the efficacy and safety of ramelteon, a selective MT1/MT2 receptor agonist, for chronic insomnia treatment. Patients and methods: Randomized, double-blind, placebo-controlled 35-night outpatient trial with weekly clinic visits at multiple centers. Patients include older adults (>= 65 years; N= 829) with chronic insomnia. Placebo, ramelteon 4 mg, or ramelteon 8 mg were taken nightly for five weeks, and patient-reported sleep data were collected using sleep diaries. Primary efficacy was sleep latency at week 1. Sustained efficacy was examined at weeks 3 and 5. Rebound insomnia and withdrawal effects were evaluated during a 7-day placebo run-out. Results: Both doses of ramelteon produced statistically significant reductions in sleep latency vs. placebo at week 1 (ramelteon 4 mg: 70.2 vs. 78.5 min, P=.008; ramelteon 8 mg: 70.2 vs. 78.5 min, P=.008). Patients continued to report reduced sleep latency at week 3 with ramelteon 8 mg (60.3 vs. 69.3 min, P=.003), and at week 5 with ramelteon 4 mg (63.4 vs. 70.6 min, P=.028) and ramelteon 8 mg (57.7 vs. 70.6 min; P <.001). Statistically significant increases in total sleep time were observed with ramelteon 4 mg at week 1 (324.6 vs. 313.9 min, P =.004) and week 3 (336.0 vs. 324.3 min, P=.007) compared with placebo. There was no evidence of significant rebound insomnia or withdrawal effects following treatment discontinuation. The incidence of adverse events was similar among all treatment groups; most were mild or moderate. Conclusions: In older adults with chronic insomnia, ramelteon significantly reduced patient reports of sleep latency over five weeks of treatment with no significant rebound insomnia or withdrawal effects. (c) 2006 Elsevier B.V. All rights reserved.