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Influence of Subchronic Intake of Melatonin at Various Times of the Day on Fatigue and Hormonal Levels: A Placebo‐Controlled, Double‐Blind Trial

In a double‐blind study, melatonin (50 mg) or placebo was administered daily to 25 subjects at 9 am or 7 pm for 1 week. Self‐rated fatigue as evaluated by the Stanford Sleepiness Scale (SSS) was significantly increased during the 3 hours following melatonin intake in the morning, whereas, after administration in the evening, no difference between melatonin and placebo could be distinguished. Sleep onset latency slightly decreased in both melatonin groups without reaching statistical significance. No cumulative effects on sleep or behavior were observed. Twelve pituitary and peripheral hormones measured under baseline and partly (in the evening groups) under stimulated conditions before and after the trial did not change. The two most important conclusions are that: 1) the sedative potency of exogenous melatonin depends on the daily time of administration; and 2) the high pharmacological doses used for acute sedation do not seem to have cumulative effects after prolonged application.