The effects of low-dose 0.5-mg melatonin on the free-running circadian rhythms of blind subjects.
Exogenous melatonin (0.5-10 mg) has been shown to entrain the free-running circadian rhythms of some blind subjects. The aim of this study was to assess further the entraining effects of a daily dose of 0.5 mg melatonin on the cortisol rhythm and its acute effects on subjective sleep in blind subjects with free-running 6-sulphatoxymelatonin (aMT6s) rhythms (circadian period [tau] 24.23-24.95 h). Ten subjects (9 males) were studied, aged 32 to 65 years, with no conscious light perception (NPL). In a placebo-controlled, single-blind design, subjects received 0.5 mg melatonin or placebo p.o. daily at 2100 h (treatment duration 26-81 days depending on individuals' circadian period). Subjective sleep was assessed from daily sleep and nap diaries. Urinary cortisol and aMT6s were assessed for 24 to 48 h weekly and measured by radioimmunoassay. Seven subjects exhibited an entrained or shortened cortisol period during melatonin treatment. Of these, 4 subjects entrained with a period indistinguishable from 24 h, 2 subjects continued to free run for up to 25 days during melatonin treatment before their cortisol rhythm became entrained, and 1 subject appeared to exhibit a shortened cortisol period throughout melatonin treatment. The subjects who entrained within 7 days did so when melatonin treatment commenced in the phase advance portion of the melatonin PRC (CT6-18). When melatonin treatment ceased, cortisol and aMT6s rhythms free ran at a similar period to before treatment. Three subjects failed to entrain with initial melatonin treatment commencing in the phase delay portion of the PRC. During melatonin treatment, there was a significant increase in nighttime sleep duration and a reduction in the number and duration of daytime naps. The positive effect of melatonin on sleep may be partly due to its acute soporific properties. The findings demonstrate that a daily dose of 0.5 mg melatonin is effective at entraining the free-running circadian systems in most of the blind subjects studied, and that circadian time (CT) of administration of melatonin may be important in determining whether a subject entrains to melatonin treatment. Optimal treatment with melatonin for this non-24-h sleep disorder should correct the underlying circadian disorder (to entrain the sleep-wake cycle) in addition to improving sleep acutely.
Centre for Chronobiology, School of Biomedical and Life Sciences, University of Surrey, Guildford, GU2 7XH, UK.
Lisa M
LM
Hack
Steven W
SW
Lockley
Josephine
J
Arendt
Debra J
DJ
Skene
D000328:Adult; D000368:Aged; D001766:Blindness; D002940:Circadian Rhythm / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000652:urine; D008297:Male; D008550:Melatonin / Q000031:analogs & derivatives* / Q000494:pharmacology* / Q000652:urine; D008875:Middle Aged; D010919:Placebos; D012890:Sleep / Q000187:drug effects / Q000502:physiology
D010919:Placebos; C054513:6-sulfatoxymelatonin; D008550:Melatonin; D006854:Hydrocortisone