Ramelteon Prior to a Short Evening Nap Impairs Neurobehavioral Performance for up to 12 Hours after Awakening

Abstract

Planned naps can improve performance when the habitual or nocturnal sleep schedule is disrupted. It may be difficult, however, to achieve sleep during a nap, particularly during the circadian peak in alertness in the early evening. Prior studies with the melatonin agonist, ramelteon, reported that this hypnotic does not impair neurobehavioral performance. We tested whether ramelteon could improve nap efficiency in the early evening and subsequent performance during a simulated 8-h night shift. 10 healthy volunteers aged 19-31 years participated in an inpatient randomized, double-blind, placebo-controlled crossover study. Ramelteon 8 mg or placebo was administered 30 min prior to a 2-h nap opportunity commencing 13 h after each individual's habitual morning wake time. Ramelteon did not significantly affect sleep efficiency during the nap prior to the night shift. Following the nap, ramelteon was associated with significantly worse neurobehavioral performance on assessments immediately following the nap and during the simulated night shift. Although ramelteon did not significantly affect sleep during the nap, it was associated with significant impairments in neurobehavioral performance for up to 12 h after administration. High homeostatic sleep pressure combined with the circadian performance nadir may increase the vulnerability to hypnotic-induced neurobehavioral impairments. The findings do not support the use of ramelteon prior to an evening prophylactic nap, as there may be residual effects that last for several hours. Furthermore, this study highlights the pitfalls of applying side-effect profiles obtained in one context to another.