Ramelteon, which acts by enhancing melatonin pathway effects, does not appear to have potential for either abuse or motor or cognitive impairment when used for sleep disturbance, according to an article in the October issue of the Archives of General Psychiatry.

Matthew W. Johnson, PhD, and colleagues at The Johns Hopkins School of Medicine, Baltimore, evaluated the potential for abuse and cognitive effects of ramelteon compared with placebo and triazolam in 14 adults with histories of abusing sedatives. During approximately 18 days, participants stayed at a residential research unit and received one of the following doses each day in random order: 16, 80 or 160 mg ramelteon (the recommended treatment dosage is 8 mg), 0.25, 0.5 or 0.75 mg triazolam, and placebo.

The patients (1 woman, 13 men; average age, 28 years) were assessed thirty minutes before taking each drug and repeatedly for the next 24 hours. They answered questions about how much they liked each drug, how strong the drug was and how alert or sleepy they felt, and also underwent cognitive and motor function tests. Trained research staff members also rated the participants' behavior, including how sedated and impaired they seemed and how much they slept.

None of the three doses of ramelteon showed any differences from placebo in effects reported by the participants, measured by performance tests or recorded by research observers.

"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," the authors wrote.

When asked the next day about the drug they had taken the night before, 11 of 14 participants (79 percent) classified the highest dose of ramelteon as placebo compared with 2 (14 percent) who categorized the highest dose of triazolam as placebo and 12 (86 percent) who classified placebo as placebo.

The findings, along with previous clinical trials indicating ramelteon's effectiveness, suggest that it "may fill an unmet need in the treatment of insomnia," the authors wrote. "Although further clinical trials are warranted, ramelteon may be particularly useful for the treatment of insomnia in individuals with histories of substance abuse, in older subjects (who are especially susceptible to the impairing effects of benzodiazepine receptor agonists), and in persons requiring minimal interference with arousal response (e.g., on-call workers and patients with chronic obstructive pulmonary disease).

“Furthermore, ramelteon may be a safe first-line medication even in individuals not reporting substance abuse, given that some individuals may not admit to such misuse."

The authors urge research on new drugs that might also act through a melatonin agonist effect.