The efficacy of melatonin and melatonin agonists in insomnia – An umbrella review

Abstract We conducted an umbrella review to summarize all available systematic reviews and meta-analyses investigating the efficacy of melatonin and melatonin agonists in primary and comorbid insomnia disorders. Two independent reviewers conducted a search of Pubmed, EMBASE, Cochrane Database of Systematic Reviews, Google Scholar, PROSPERO and grey literature from inception to July 2018. Methodological quality was assessed using the revised Assessment of Multiple Systematic Reviews Instrument. Eighteen studies were found, with methodological quality ranging from Moderate to Critically Low. Of the twelve papers evaluating melatonin, there is statistically significant improvement in sleep latency and total sleep time, with a lack of consensus on whether these are clinically meaningful. Similar results are observed across the three reviews on ramelteon. The evidence for other melatonin agonists is sparse. We conclude that existing evidence is limited by disparate methodological quality of the papers, as well as a lack of consensus regarding the type, definition and interpretation of outcome measures in the evaluation of efficacy for insomnia.