Efficacy and clinical safety of ramelteon: an evidence-based review

Ramelteon is a novel hypnotic compound that is FDA-approved for the treatment of sleep-onset difficulty. It is a melatonin 1/2 receptor agonist with rapid absorption, extensive first-pass metabolism and an elimination half-life of just over 1h. Clinical efficacy data indicate moderate efficacy in reduction of sleep latency in adults of all ages with chronic insomnia, with estimated effect sizes roughly comparable to other standard hypnotic agents. Objective studies show minimal increases in total sleep time and no significant impact on wake after sleep-onset or sleep-stage distribution. Subjective reports demonstrate comparable, if slightly smaller, improvements. The recommended dosage is 8mg but studies suggest a flat response across dosage ranges from 4 to 32mg. Safety data indicate no evidence of clinically significant next-day performance effects and a reasonably low side effect profile. Animal studies, and a single human study suggest low abuse potential. Single-blind run-out from clinical trials have demonstrated no evidence of rebound insomnia.