Ramelteon: a novel hypnotic lacking abuse liability and sedative adverse effects.

Context: Ramelteon is a novel MT1 and MT2 melatonin receptor selective agonist recently approved for insomnia treatment. Most approved insomnia medications have potential for abuse and cause motor and cognitive impairment.

Objective: To evaluate the potential for abuse, subjective effects, and motor and cognitive-impairing effects of ramelteon compared with triazolam, a classic benzodiazepine sedative-hypnotic drug.

Design: In this double-blind crossover study, each participant received oral doses of ramelteon (16, 80, or 160 mg), triazolam (0.25, 0.5, or 0.75 mg), and placebo during approximately 18 days. All participants received each treatment on different days. Most outcome measures were assessed at 0.5 hours before drug administration and repeatedly up to 24 hours after drug administration.

Setting: Residential research facility.

Participants: Fourteen adults with histories of sedative abuse.

Main Outcome Measures: Subject-rated measures included items relevant to potential for abuse (eg, drug liking, street value, and pharmacological classification), as well as assessments of a broad range of stimulant and sedative subjective effects. Observer-rated measures included assessments of sedation and impairment. Motor and cognitive performance measures included psychomotor and memory tasks and a standing balance task.

Results: Compared with placebo, ramelteon (16, 80, and 160 mg) showed no significant effect on any of the subjective effect measures, including those related to potential for abuse. In the pharmacological classification, 79% (11/14) of subjects identified the highest dose of ramelteon as placebo. Similarly, compared with placebo, ramelteon had no effect at any dose on any observer-rated or motor and cognitive performance measure. In contrast, triazolam showed dose-related effects on a wide range of subject-rated, observer-rated, and motor and cognitive performance measures, consistent with its profile as a sedative drug with abuse liability.

Conclusion: Ramelteon demonstrated no significant effects indicative of potential for abuse or motor and cognitive impairment at up to 20 times the recommended therapeutic dose and may represent a useful alternative to existing insomnia medications.