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From the Department of Psychiatry, University of Toronto, and Sleep Research Laboratory, University Health Network, Toronto Western Hospital (L.K., G. B., R.J., C.M.S.); Toronto Western Research Institute, University of Toronto (L.K., C.M.S.); and Ajax-Pickering General Hospital (K.B.), Pickering, Ontario, Canada.
Dr. Leonid Kayumov, Department of Psychiatry, University of Toronto and University Health Network, Toronto Western Hospital, MP 10-320, 399 Bathurst St., Toronto, ON, M5T 2S8, Canada. Email: lkayumov{at}playfair.utoronto.ca
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 24:00 to 08:00 hours. This study was a randomized, double-blind, placebo-controlled crossover trial. Subjects received either placebo or melatonin (5 mg) daily for 4 weeks, underwent a 1-week washout period, and then were given the other treatment for an additional 4 weeks. Patients could take the melatonin between 19:00 and 21:00 hours, which allowed them to select the time they felt to be most beneficial for the phase-setting effects of the medication.
METHODS: Two consecutive overnight polysomnographic recordings were performed on three occasions: at baseline (before treatment), after 4 weeks of melatonin treatment, and after 4 weeks of placebo treatment.
RESULTS: In the 20 patients who completed the study, sleep onset latency was significantly reduced while subjects were taking melatonin as compared with both placebo and baseline. There was no evidence that melatonin altered total sleep time (as compared with baseline total sleep time), but there was a significant decrease in total sleep time while patients were taking placebo. Melatonin did not result in altered scores on subjective measures of sleepiness, fatigue, and alertness, which were administered at different times of the day. After an imposed conventional sleep period (from 24:00 to 08:00), subjects taking melatonin reported being less sleepy and fatigued than they did while taking placebo.
CONCLUSIONS: Melatonin ameliorated some symptoms of delayed sleep phase syndrome, as confirmed by both objective and subjective measures. No adverse effects of melatonin were noted during the 4-week treatment period.
Key Words: melatonin • delayed sleep phase syndrome • sleep • circadian rhythms.
Abbreviations: aMT6s = sulfatoxymelatonin; CES-D = Center for Epidemiologic Studies Depression Scale; DSPS = delayed sleep phase syndrome; HAM-D = Hamilton Depression Scale; REM = rapid eye movement; SOL = sleep onset latency; SSS = Stanford Sleepiness Scale; TST = total sleep time; WASO = wakefulness after sleep onset.
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