In a study of 14 adults with histories of sedative abuse, the newly approved sleep medication ramelteon does not appear to have effects that indicate potential for abuse or motor or cognitive impairment, according to a report in the October issue of Archives of General Psychiatry, one of the JAMA/Archives journals.

About 10 to 15 percent of adults regularly experience chronic insomnia, difficulty sleeping that causes distress or impaired daytime functioning, according to background information in the article. Some of the medications most commonly used to treat the condition (known as benzodiazepine receptor agonists) have a number of problematic side effects.

These include a risk for abuse, especially by those with histories of substance abuse; difficulties with cognition (thinking, learning and memory), including a type of amnesia that blocks the formation of new memories; and motor impairments that may make driving dangerous and contribute to falls among older adults. In addition, those who use benzodiazepine receptor agonists long-term may experience withdrawal symptoms - including anxiety, irritability and even seizures - if they stop taking the drugs. Ramelteon, a drug recently approved for treatment of insomnia, works through a different pathway in the brain involving melatonin receptors and therefore may be less likely to cause such effects.

Matthew W. Johnson, Ph.D., and colleagues at The Johns Hopkins School of Medicine, Baltimore, evaluated the potential for abuse and cognitive effects of ramelteon compared with placebo and with triazolam, a benzodiazepine, among 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 of drugs each day in random order: 16, 80 or 160 milligrams of ramelteon (the recommended treatment dosage is 8 milligrams); .25, .5 or .75 milligrams of triazolam; and placebo. The patients, including one woman and 13 men with an average age of 28, 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 write. When asked the next day about the drug they had taken the day before, 11 of the 14 participants (79 percent) classified the highest dose of ramelteon as a placebo, compared with two (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 write. “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.” Future research on sleep medications should explore the effectiveness of other drugs that work on the same pathway as ramelteon, they conclude.

(Arch Gen Psychiatry. 2006;63:1149-1157. Available pre-embargo to the media at http://www.jamamedia.org.)