Adverse events in long-term studies of exogenous melatonin

Exogenous melatonin is regulated as a drug in the UK and EU but is available as an over-the-counter dietary supplement in the US and Canada. In the last 15 years, melatonin use has increased rapidly in many countries, in particular, in children and adolescents who frequently have many years of continuous exposure. Despite this, the potential risks associated with extended use continue to be unclear, and there remains a lack of systematically assessed safety data from long-term prospective trials.

This review focuses on adverse event data reported in long-term (≥6 months) prospective trials of melatonin.

The Embase and Medline electronic databases were searched from inception to 12 September 2022 for long-term studies of melatonin, in which adverse events were systematically monitored and reported.

Although the reported frequency of possible adverse events associated with long-term melatonin use is low and few clinically significant adverse events have been reported, the scarcity of data from double-blind randomized placebo-controlled trials should caution against complacency. Ideally, analysis of data from large well-established research databases should be conducted to provide good quality evidence on which to base a more rigorous evaluation of the safety profile.