CLINICAL REVIEWEffects of exogenous melatonin on sleep: a meta-analysis
Introduction
The extensive reporting about melatonin in lay publications has encouraged very many people to consume this hormone, sometimes on a daily basis, often with the goal of improving sleep quality.1 In humans, the circadian rhythm of melatonin release from the pineal gland is highly synchronized with the habitual hours of sleep, and the daily onset of melatonin secretion is well correlated with the onset of the steepest increase in nocturnal sleepiness (‘sleep gate’).2 Serum melatonin levels were reported to be significantly lower (and the time of peak melatonin values was delayed) in elderly subjects with insomnia, compared with age-matched subjects with no insomnia.3
There are also a number of reports that physiological doses of melatonin (i.e. doses which elevate plasma melatonin within its normal nocturnal range), or pharmacologic doses, induce drowsiness and sleep, and may ameliorate sleep disturbances.4., 5. Unfortunately, the studies described in existing publications on melatonin's efficacy have utilized different inclusion and exclusion criteria, different outcome measures to evaluate insomnia, different doses of the hormone, and different routes and timing of its administration. Adding to this complexity, there continues to be considerable controversy over the meaning of the discrepancies that sometimes exist between subjective and objective (polysomnographic) measures of good and bad sleep.6 In an attempt to respond to these problems we have therefore integrated information derived from 17 studies*3., 7., 8., 9., 10., *11., 12., *13., 14., *15., 16., *17., *18., 19., *20., *21., 22. which fulfill the criteria described below, using meta-analysis. To our knowledge, while several reviews have examined the effects of melatonin on sleep and insomnia, none has provided a quantitative meta-analysis of these effects, as presented below.
Section snippets
Material and methods
The meta-analysis is based on data reported in peer-reviewed scientific journals. Studies that included at least six adult subjects with no severe disabling systemic disease; were randomized and double blinded; involved placebo-controlled clinical trials; and used objective measures of sleep evaluation were eligible for inclusion in the meta-analysis. Both crossover and parallel group designs were included but case reports were excluded (Appendix A). We identified 17 studies (Table 1) which met
Results
Summary statistics and overall P-values for comparisons among treatment groups were abstracted from the source publications and are displayed graphically in Figure 1, Figure 2, Figure 3. These data are the source data for the conduct of the meta-analysis.
Discussion
This meta-analysis supports the hypotheses that melatonin decreases sleep onset latency, increases sleep efficiency, and increases total sleep duration. The pooled data were highly heterogeneous, possibly reflecting the fact that the melatonin preparations used in these individual studies varied in dose presented, and probably in quality, excipients, and purity as well. In addition, the study designs differed considerably from each other. Nevertheless, in spite of the heterogeneity of the data,
Acknowledgements
These studies were supported in part by NIH Grants 5M01 RR1066-25 to the MIT Clinical Research Center, The National Institutes of Health (MH-28783), and from the Center for Brain Sciences and Metabolism Charitable Trust and the Women' Health Center, Hadassah–Hebrew University Medical Center.
References (29)
- et al.
Delayed sleep phase syndrome response to melatonin
Lancet
(1991) - et al.
Improvement of sleep quality by melatonin
Lancet
(1995) - et al.
Effect of controlled-release melatonin on sleep quality, mood, and quality of life in subjects with seasonal or weather-associated changes in mood and behaviour
Eur Neuropsychopharm
(2003) Melatonin in humans
New Engl J Med
(1997)- et al.
Melatonin: the key to the gate of sleep
Ann Med
(1998) - et al.
Melatonin replacement therapy of elderly insomniacs
Sleep
(1995) - et al.
Melatonin—a sleep-promoting hormone
Sleep
(1997) - et al.
Melatonin for treatment of sleep and mood disorders
- et al.
Benzodiazepines and zolpidem for chronic insomnia: a meta-analysis of treatment efficacy
JAMA
(1997) - et al.
Low dose melatonin improves sleep in healthy middle-aged subjects
Psychopharm
(1996)
On the effects of melatonin on sleep and behaviour in man
Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance
Proc Natl Acad Sci
of sleep quality in elderly people by controlled-release melatonin
Lancet
Sleep-promoting and hypothermic effects of daytime melatonin administration in humans
Sleep
Cited by (416)
The Effect of Melatonin on Analgesia, Anxiety, and Intraocular Pressure (IOP) in Cataract Surgery Under Topical Anesthesia
2023, Journal of Perianesthesia NursingThe Utility of Melatonin for the Treatment of Sleep Disturbance After Traumatic Brain Injury: A Scoping Review
2023, Archives of Physical Medicine and RehabilitationTryptophan and melatonin as treatments
2023, Encyclopedia of Sleep and Circadian Rhythms: Volume 1-6, Second EditionThe role of pharmacological interventions for sleep deprivation and restriction
2023, Encyclopedia of Sleep and Circadian Rhythms: Volume 1-6, Second Edition
- 1
Tel.: +972-2-6777-111; fax: +972-2-643-3337.
- 2
Tel.: +1-617-253-0060; fax: +1-617-258-5026.
- 3
Tel.: +44-141-330-4744; fax: +44-141-330-5094.
- 4
Tel.: +1-617-638-4187; fax: +1-617-638-4676.