A randomized, double-blind, placebo-controlled crossover study of the effect of exogenous melatonin on delayed sleep phase syndrome

Objective: The effects of exogenous melatonin on sleep, daytime sleepiness, fatigue, and alertness were investigated in 22 patients with delayed sleep phase syndrome whose nocturnal sleep was restricted to the interval from 2 4:00 to 08:00 hours. This study was a randomized, double-blind, placebo-con trolled crossover trial. Subjects received either placebo or melatonin (5 m g) daily for 4 weeks, underwent a 1-week washout period, and then were give n the other treatment for an additional 4 weeks. Patients could take the me latonin between 19:00 and 21:00 hours, which allowed them to select the tim e they felt to be most beneficial for the phase-setting effects of the medi cation, Methods: Two consecutive overnight polysomnographic recordings were performed on three occasions: at baseline (before treatment), after 4 week s of melatonin treatment, and after 4 weeks of placebo treatment. Results: In the 20 patients who completed the study, sleep onset latency was signifi cantly reduced while subjects were taking melatonin as compared with both p lacebo and baseline. There was no evidence that melatonin altered total sle ep time las compared with baseline total sleep time), but there was a signi ficant decrease in total sleep time while patients were taking placebo. Mel atonin did not result in altered scores on subjective measures of sleepines s, fatigue, and alertness, which were administered at different times of th e day. After an imposed conventional sleep period (from 24:00 to 08:00), su bjects taking melatonin reported being less sleepy and fatigued than they d id while taking placebo. Conclusions: Melatonin ameliorated some symptoms o f delayed sleep phase syndrome, as confirmed by both objective and subjecti ve measures. No adverse effects of melatonin were noted during the 4-week t reatment period.