Elsevier

Sleep Medicine Reviews

Volume 34, August 2017, Pages 10-22
Sleep Medicine Reviews

Clinical Review
Evidence for the efficacy of melatonin in the treatment of primary adult sleep disorders

https://doi.org/10.1016/j.smrv.2016.06.005Get rights and content

Summary

Melatonin is a physiological hormone involved in sleep timing and is currently used exogenously in the treatment of primary and secondary sleep disorders with empirical evidence of efficacy, but very little evidence from randomised, controlled studies. The aim of this meta-analysis was to assess the evidence base for the therapeutic effects of exogenous melatonin in treating primary sleep disorders.

An electronic literature review search of MEDLINE (1950-present) Embase (1980- present), PsycINFO (1987- present), and Scopus (1990- present), along with a hand-searching of key journals was performed in July 2013 and then again in May 2015. This identified all studies that compared the effect of exogenous melatonin and placebo in patients with primary insomnia, delayed sleep phase syndrome, non 24-h sleep wake syndrome in people who are blind, and rapid eye movement-behaviour disorder. Meta-analyses were performed to determine the magnitude of effect in studies of melatonin in improving sleep.

A total of 5030 studies were identified; of these citations, 12 were included for review based on the inclusion criteria of being: double or single-blind, randomised and controlled. Results from the meta-analyses showed the most convincing evidence for exogenous melatonin use was in reducing sleep onset latency in primary insomnia (p = 0.002), delayed sleep phase syndrome (p < 0.0001), and regulating the sleep-wake patterns in blind patients compared with placebo.

These findings highlight the potential importance of melatonin in treating certain first degree sleep disorders. The development of large-scale, randomised, controlled trials is recommended to provide further evidence for therapeutic use of melatonin in a variety of sleep difficulties.

Section snippets

Melatonin use in sleep disorders

Clinically significant sleep disorders affect at least 10% of Western populations, and one third or more of the population suffers daily from a sleep disturbance or excessive daytime sleepiness [1]. Management of many of these sleep disorders often requires complex therapeutic regimens, involving both pharmacological and non-pharmacological interventions.

When considering pharmacological management of sleep disorders, drugs which have a short half-life are preferable to minimise ‘hangover’

Biology of melatonin

In humans, the primary physiological function of melatonin is to reinforce darkness-related behaviour, such as sleep propensity [15]. Inadequate sleep can not only lead to a reduction in daytime performance and excessive sleepiness, but chronic inadequate sleep may lead to immunosuppression and increased cancer-stimulatory cytokine production [16].

Endogenous melatonin synthesis is finely regulated by visual light cues received by the hypothalamic suprachiasmatic nucleus in the brain, the site

Method

A meta-analysis was performed including the published, peer-reviewed randomised controlled trials (RTC) on the use of exogenous melatonin to treat primary sleep disorders that we included in this review.

Search strategy

The databases used to search the literature for this review were MEDLINE (1950- present), Embase (1980- present), PsycINFO (1987- present), and Scopus (1990- present). These databases allowed for a wide range of clinical medical material to be covered over a broad base of global journals [35].

Results

A total of 5030 articles were identified in the initial database and hand search (3696 Embase, 790 MEDLINE, 496 PsycINFO, 48 Scopus) of journals. From this, 361 abstracts were assessed and 27 met inclusion criteria. Fifteen articles were then excluded for reasons described below, resulting in a final 12 which were included (Fig. 1). The studies included in analysis comprised a total of 1510 patients, all aged between 18 and 80 y with either primary insomnia, DSPS, blindness, or RBD. Each study

Discussion

This review has shown evidence that melatonin has a role in the treatment of some primary sleep disorders, namely primary insomnia, DSPS, non-24 h sleep-wake disorder and in people who are blind. There is some evidence that melatonin may be beneficial for those with RBD, but more research is required to draw this conclusion. Melatonin facilitates achieving better sleep for these patients by reducing the sleep-onset latency [52] or by regulating sleep-wake times to coincide with the natural

Conflicts of interest

The authors report no conflict of interest in the preparation of this work.

Acknowledgements

Sincere thanks to Lisa Wood and Tomas Ray for assistance with editing.

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