Long-term safety and efficacy of ramelteon in Japanese patients with chronic insomnia.

Objective: To evaluate the safety of ramelteon, a highly selective MT₁/MT₂ melatonin receptor agonist, during 24 weeks' treatment of Japanese patients with chronic insomnia.

Methods: In a single-blind, flexible-titration, multicenter study incorporating placebo run-in and run-out periods, 190 adults with chronic insomnia received ramelteon 4 or 8 mg, titrated up to 16 mg if necessary, for 24 weeks. Primary endpoints included adverse events, residual effects, rebound insomnia, withdrawal symptoms, and dependence. Secondary endpoints included subjective sleep latency and total sleep time.

Results: Drug-related adverse events occurred in 11.6% of patients. No clinically important changes occurred in biochemical, hematological or endocrine parameters. There were no signs of next-day residual effect, rebound insomnia, withdrawal symptoms or dependence. Mean subjective sleep latency decreased significantly, and total sleep time increased significantly; both reached a plateau by week 20 and were sustained thereafter (P<0.0001).

Conclusions: Ramelteon was well tolerated in adult Japanese patients with chronic insomnia and did not cause deterioration of efficacy, residual effects, rebound insomnia, withdrawal symptoms, or dependence after 24 weeks' treatment.