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

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.