Sleep-facilitating effect of exogenous melatonin in healthy young men and women is circadian-phase dependent

Study Objectives: To investigate the effects of a physiologic and a pharmacologic dose of exogenous melatonin on sleep latency and sleep efficiency in sleep episodes initiated across a full range of circadian phases. Design: Double-blind placebo-controlled parallel-group design in a 27-day forced desynchrony paradigm with a 20-hour scheduled sleep-wake cycle. Setting: Private suite of a general clinical research center, in the absence of time-of-day information. Subjects: Thirty-six healthy, 18- to 30-year-old, men (n = 21) and women (n = 15). Interventions: Oral melatonin (0.3 mg or 5.0 mg) or identical-appearing placebo was administered 30 minutes prior to each 6.67-hour sleep episode during forced desynchrony. Measurements and Results: Both doses of melatonin improved polysomnographically determined sleep efficiency from 77% in the placebo group to 83% for sleep episodes occurring during circadian phases when endogenous melatonin was absent. However, this remained below the average sleep efficiency of 88% observed during sleep episodes scheduled during the circadian night, when endogenous melatonin was present. Melatonin did not significantly affect sleep initiation or core body temperature. Melatonin appeared to maintain efficacy across the study and did not significantly affect percentages of slow-wave sleep or rapid eye movement sleep. Conclusions: Exogenous melatonin administration possesses circadian-phase-dependent hypnotic properties, allowing for improved consolidation of sleep that occurs out of phase with endogenous melatonin secretion during the circadian night. The results support the hypothesis that both exogenous and endogenous melatonin attenuate the wake-promoting drive from the circadian system.