P076 Safety of higher doses of melatonin in adults: A systematic review and meta-analysis

Abstract

Abstract Introduction Melatonin is commonly used for sleep and jetlag at low doses. There is less documentation on the safety of higher doses which are being increasingly used for a wide variety of conditions. This systematic review aimed to investigate the safety of higher doses of melatonin in adults. Methods We searched Medline, Scopus, Embase and PsycINFO databases from study inception until December 2019 with convenience searches until October 2020. The inclusion criteria were randomised controlled trials investigating high-dose melatonin (≥10mg) in human adults over 30 years of age. The outcomes examined were the number of adverse events (AEs), serious adverse events (SAEs) and withdrawals due to AEs. A meta-analysis was conducted on studies lasting 3 months or longer. Results 79 studies were identified with a total of 3861 participants. 29 studies (37%) made no mention of the presence or absence of AEs. Only 4 studies met the pre-specified low-risk of bias criteria for meta-analysis. In that small subset, melatonin did not cause a detectable increase in SAEs (Rate Ratio=0.88 [0.52, 1.50], p=0.64) or withdrawals due to AEs (0.93 [0.24, 3.56], p=0.92), but did appear to increase the risk of AEs such as drowsiness, headache, and dizziness (1.40, [1.15, 1.69], p<0.001). Discussion There has been limited AE reporting from high-dose melatonin studies. Based on this limited evidence, melatonin appears to have a good safety profile. Better safety reporting in future long-term trials is needed to confirm this as our confidence limits were very wide due to the paucity of suitable data.