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The effects of low-dose 0.5-mg melatonin on the free-running circadian rhythms of blind subjects

Hack, L.M., Lockley, S.W., Arendt, J. and Skene, D.J. (2003) The effects of low-dose 0.5-mg melatonin on the free-running circadian rhythms of blind subjects Journal of Biological Rhythms, 18 (5). pp. 420-429.

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Abstract

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 [�] 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.

Item Type: Article
Authors :
NameEmailORCID
Hack, L.M.
Lockley, S.W.s.lockley@surrey.ac.uk
Arendt, J.
Skene, D.J.
Date : 2003
DOI : 10.1177/0748730403256796
Uncontrolled Keywords : Blindness, Circadian rhythms, Cortisol, Melatonin, Napping, Sleep, 6 hydroxymelatonin o sulfate, hydrocortisone, melatonin, adult, aged, article, blindness, circadian rhythm, clinical article, controlled study, correlation analysis, drug effect, hormonal regulation, human, hydrocortisone urine level, male, radioimmunoassay, regulatory mechanism, sleep waking cycle, time series analysis, Adult, Aged, Blindness, Circadian Rhythm, Female, Humans, Hydrocortisone, Male, Melatonin, Middle Aged, Placebos, Sleep
Depositing User : Clive Harris
Date Deposited : 17 Jun 2020 02:01
Last Modified : 17 Jun 2020 02:01
URI: http://epubs.surrey.ac.uk/id/eprint/857950

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