Efficacy and safety of 6-month nightly ramelteon administration in adults with chronic primary insomnia.

STUDY OBJECTIVES: Long-duration (> or = 6 months) polysomnographic studies of insomnia medications are lacking. This study evaluated the long-term efficacy of ramelteon, a selective MT1/MT2 melatonin-receptor agonist used for insomnia treatment.

DESIGN: Six-month, randomized, double-blind, placebo-controlled study.

SETTING: Forty-six investigative sites in the United States, Europe, Russia, and Australia.

PARTICIPANTS: Four hundred fifty-one adults (age > or = 18 years) with chronic primary insomnia.

INTERVENTIONS: Ramelteon, 8 mg, or placebo 30 minutes before bedtime nightly for 6 months.

MEASUREMENTS: Sleep was evaluated by polysomnography and morning questionnaires on the first 2 nights of Week 1; the last 2 nights of Months 1, 3, 5, and 6; and Nights 1 and 2 of the placebo run-out. Next-morning residual effects as well as adverse effects and vital signs were recorded at each visit. Rebound insomnia and withdrawal effects were evaluated during placebo run-out.

RESULTS: Over the 6 months of treatment, ramelteon consistently reduced latency to persistent sleep compared with baseline and with placebo; significant decreases were observed at Week 1 and Months 1, 3, 5, and 6 (P < 0.05). Ramelteon significantly reduced subjective sleep latency relative to placebo at Week 1, Month 1, and Month 5 (P < 0.05), with reductions nearing statistical significance at Months 3 and 6 (P < or = 0.08). No significant next-morning residual effects were detected during ramelteon treatment. No withdrawal symptoms or rebound insomnia were detected after ramelteon discontinuation. Most adverse events were mild or moderate in severity.

CONCLUSIONS: In adults with chronic insomnia, long-term ramelteon treatment consistently reduced sleep onset, with no next-morning residual effects or rebound insomnia or withdrawal symptoms upon discontinuation.