A 2-night, 3-period, crossover study of ramelteon's efficacy and safety in older adults with chronic insomnia

ABSTRACT

Objective: To assess the efficacy and safety of ramelteon, a selective melatonin MT₁/MT₂-receptor agonist, for insomnia treatment in older adults.

Methods: In a randomized, 9‑week, 3‑period crossover trial conducted at 17 sleep centers, older adults (N = 100) with chronic primary insomnia (37 men, 63 women; mean age [range], 70.7 [65–83] years) were administered placebo, ramelteon 4 mg, and ramelteon 8 mg in three treatment phases for two consecutive nights. Each phase was separated by 5- to 12‑day washout periods. Sleep was monitored via polysomnography. Subjective sleep parameters, using a Postsleep Questionnaire, were recorded, and residual pharmacologic effects were assessed.

Results: Statistically significant reductions in latency to persistent sleep were observed with both ramelteon 4 mg and 8 mg compared to placebo (28.7 min vs. 38.4 min, p < 0.001; 30.8 min vs. 38.4 min, p = 0.005, respectively). Total sleep time (p = 0.036 and p = 0.007,respectively) and sleep efficiency (p = 0.037 and p = 0.007, respectively) were also significantly improved with ramelteon 4 mg and 8 mg compared to placebo. Statistically significant reductions in subjective sleep latency on a Postsleep Questionnaire were reported with ramelteon 4 mg versus placebo (p = 0.037), but not ramelteon 8 mg (p = 0.120); no significant differences on other subjective sleep assessments were reported. A lack of power limits interpretation of self-reported sleep parameters. Incidences of adverse events considered treatment related were placebo (7%), ramelteon 4 mg (11%), and ramelteon 8 mg (5%). No residual pharmacologic effects were observed via Digit Symbol Substitution Test, memory recall tests (immediate and delayed), visual analog scales (feelings and mood), and Postsleep Questionnaire (level of alertness and ability to concentrate).

Conclusions: In older adults with chronic primary insomnia, ramelteon produced significant reductions in latency to persistent sleep and increases in total sleep time and sleep efficacy, and showed no evidence of adverse next-day psychomotor or cognitive effects.

Key words: :

• Chronic insomnia
• Elderly
• Melatonin
• MT1/MT2-receptor agonists