Article

Effects of exogenous melatonin on sleep: A meta-analysis. Sleep Med Rev 9: 41-50

Department of Obstetrics and Gynecology, Hadassah Medical Center, Jerusalem, Israel.
Sleep Medicine Reviews (Impact Factor: 8.51). 03/2005; 9(1):41-50. DOI: 10.1016/j.smrv.2004.06.004
Source: PubMed

ABSTRACT

Exogenous melatonin reportedly induces drowsiness and sleep, and may ameliorate sleep disturbances, including the nocturnal awakenings associated with old age. However, existing studies on the soporific efficacy of melatonin have been highly heterogeneous in regard to inclusion and exclusion criteria, measures to evaluate insomnia, doses of the medication, and routes of administration. We reviewed and analyzed (by meta-analysis) available information on effects of exogenous melatonin on sleep. A MEDLINE search (1980 to December 2003) provided English-language articles, supplemented by personal files maintained by the authors. The analysis used information derived from 17 different studies (involving 284 subjects) that satisfied inclusion criteria. Sleep onset latency, total sleep duration, and sleep efficiency were selected as the outcome measures. The study effect size was taken to be the difference between the response on placebo and the mean response on melatonin for each outcome measured. Melatonin treatment significantly reduced sleep onset latency by 4.0 min (95% CI 2.5, 5.4); increased sleep efficiency by 2.2% (95% CI 0.2, 4.2), and increased total sleep duration by 12.8 min (95% CI 2.9, 22.8). Since 15 of the 17 studies enrolled healthy subjects or people with no relevant medical condition other than insomnia, the analysis was also done including only these 15 studies. The sleep onset results were changed to 3.9 min (95% CI (2.5, 5.4)); sleep efficiency increased to 3.1% (95% CI (0.7, 5.5)); sleep duration increased to 13.7 min (95% CI (3.1, 24.3)).

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    • "Pharmacological doses of exogenous melatonin have been proven to be effective in disorders of the circadian rhythm such as jetlag, shift work, delayed sleep phase syndrome, or irregular rhythm in blind people (Arendt et al., 1986; Arendt et al., 1988; Arendt and Skene, 2005; Dawson et al., 1995; Sack et al., 2000). More doubts exist on the soporific effect of melatonin (Brzezinski et al., 2005; Ferracioli-Oda et al., 2013). In diurnal vertebrates, the endogenous melatonin profile is strongly related to sleep (Shochat et al., 1997), and its prolonged-release formulation is approved for the treatment of old-age insomnia (Garfinkel et al., 1995; Lemoine et al., 2007; Wade et al., 2011). "
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    ABSTRACT: Melatonin is secreted systemically from the pineal gland maximally at night but is also produced locally in many tissues. Its chronobiological function is mainly exerted by pineal melatonin. It is a feedback regulator of the main circadian pacemaker in the hypothalamic suprachiasmatic nuclei and of many peripheral oscillators. Although exogenous melatonin is approved for circadian rhythm sleep disorders and old-age insomnia, research on endogenous melatonin in humans is hindered by the great interindividual variability of its amount and circadian rhythm. Single case studies on pinealectomized patients report on disrupted but also hypersomnic sleep. This is the first systematic prospective report on sleep with respect to pinealectomy due to pinealocytoma World Health Organization grade I without chemo- or radiotherapy. Before and after pinealectomy, 8 patients completed questionnaires on sleep quality and circadian rhythm (Pittsburgh Sleep Quality Index, Epworth Sleepiness Scale, and Morningness-Eveningness Questionnaire), 2 nights of polysomnography, salivary evening melatonin profiles, and qualitative assessment of 2 weeks of actigraphy and sleep logs. Six patients were assessed retrospectively up to 4 years after pinealectomy. Before pinealectomy, all but 1 patient showed an evening melatonin rise typical for indifferent chronotypes. After pinealectomy, evening saliva melatonin was markedly diminished, mostly below the detection limit of the assay (0.09 pg/mL). No systematic change in subjective sleep quality or standard measures of polysomnography was found. Mean pre- and postoperative sleep efficiency was 94% and 95%, and mean sleep-onset latency was 21 and 17 min, respectively. Sleep-wake rhythm during normal daily life did not change. Retrospective patients had a reduced sleep efficiency (90%) and more stage changes, although this was not significantly different from prospective patients. In conclusion, melatonin does seem to have a modulatory, not a regulatory, effect on standard measures of sleep. Study output is limited by small sample size and because only evening melatonin profiles were assessed.
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    • "There is little evidence to suggest that it has important effects in normal sleepers if given at habitual bedtime. The effects of melatonin on sleep have been extensively reviewed recently (Brzezinski et al., 2005; and see this issue). "
    Article: Melatonin
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    ABSTRACT: Melatonin (N-acetyl-5-methoxytryptamine) is synthesised largely in the pineal gland at night with a marked circadian rhythm, driven by a central 'clock' the suprachiasmatic nuclei of the hypothalamus. Light suppresses production and synchronises the rhythm to 24. h. Melatonin signals time of day and time of year to body physiology by its profile of secretion. This signal is used to time seasonal functions e.g. reproduction, coat growth, timing of puberty in photoperiodic species, via melatonin receptors on the pars tuberalis of the pituitary stalk. Endogenous melatonin reinforces the functioning of the human circadian system, notably sleep and the core body temperature rhythm. In large doses and in vitro it has anti-oxidant and neuroprotective properties. The melatonin rhythm is the best peripheral index of the timing of the human circadian 'clock.' Exogenous melatonin acts as a 'chronobiotic' and a soporific, acting, at least in part, via melatonin receptors in the SCN. Agonists and antagonists to melatonin receptors MT1 and MT2, have been developed. It has been most successful as a timed treatment for circadian rhythm related sleep disorders.
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    • "Moreover the optimal dose of MLT is not defined and is consensual (Gitto et al., 2011). After an oral administration of a fast-release dosage form, the peak concentration is reached on average within 60 min (Brezezinski et al., 2005) as MLT is hepatically metabolized, with 80–90% converted to 6-sulphatox- ymelatonin, an inactive compound excreted in the urine. Dietary supplements with prolonged MLT release are now available in the market. "

    Full-text · Article · Jul 2014 · International Journal of Pharmaceutics
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