PMID- 34923676 OWN - NLM STAT- MEDLINE DCOM- 20220218 LR - 20220218 IS - 1600-079X (Electronic) IS - 0742-3098 (Linking) VI - 72 IP - 2 DP - 2022 Mar TI - Safety of higher doses of melatonin in adults: A systematic review and meta-analysis. PG - e12782 LID - 10.1111/jpi.12782 [doi] AB - Melatonin is commonly used for sleep and jetlag at low doses. However, there is less documentation on the safety of higher doses, which are being increasingly used for a wide variety of conditions, including more recently COVID-19 prevention and treatment. The aim of this review was to investigate the safety of higher doses of melatonin in adults. Medline, Scopus, Embase and PsycINFO databases from inception until December 2019 with convenience searches until October 2020. Randomised controlled trials investigating high-dose melatonin (>/=10 mg) in human adults over 30 years of age were included. Two investigators independently abstracted articles using PRISMA guidelines. Risk of bias was assessed by a committee of three investigators. 79 studies were identified with a total of 3861 participants. Studies included a large range of medical conditions. The meta-analysis was pooled data using a random effects model. The outcomes examined were the number of adverse events (AEs), serious adverse events (SAEs) and withdrawals due to AEs. A total of 29 studies (37%) made no mention of the presence or absence of AEs. Overall, only four 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 = .64) or withdrawals due to AEs (0.93 [0.24, 3.56], p = .92), but did appear to increase the risk of AEs such as drowsiness, headache and dizziness (1.40 [1.15, 1.69], p < .001). Overall, 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. CI - (c) 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. FAU - Menczel Schrire, Zoe AU - Menczel Schrire Z AUID- ORCID: 0000-0001-9903-0899 AD - Healthy Brain Ageing Program, Faculty of Science, School of Psychology, The University of Sydney, Sydney, New South Wales, Australia. AD - Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia. AD - Brain & Mind Centre, The University of Sydney, Sydney, New South Wales, Australia. AD - Woolcock Institute of Medical Research, Centre for Sleep and Chronobiology, University of Sydney, Sydney, New South Wales, Australia. FAU - Phillips, Craig L AU - Phillips CL AD - Woolcock Institute of Medical Research, Centre for Sleep and Chronobiology, University of Sydney, Sydney, New South Wales, Australia. AD - Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia. FAU - Chapman, Julia L AU - Chapman JL AD - Healthy Brain Ageing Program, Faculty of Science, School of Psychology, The University of Sydney, Sydney, New South Wales, Australia. AD - Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia. AD - Brain & Mind Centre, The University of Sydney, Sydney, New South Wales, Australia. AD - Woolcock Institute of Medical Research, Centre for Sleep and Chronobiology, University of Sydney, Sydney, New South Wales, Australia. FAU - Duffy, Shantel L AU - Duffy SL AD - Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia. AD - Brain & Mind Centre, The University of Sydney, Sydney, New South Wales, Australia. AD - Woolcock Institute of Medical Research, Centre for Sleep and Chronobiology, University of Sydney, Sydney, New South Wales, Australia. AD - Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia. FAU - Wong, Grace AU - Wong G AD - Woolcock Institute of Medical Research, Centre for Sleep and Chronobiology, University of Sydney, Sydney, New South Wales, Australia. FAU - D'Rozario, Angela L AU - D'Rozario AL AD - Healthy Brain Ageing Program, Faculty of Science, School of Psychology, The University of Sydney, Sydney, New South Wales, Australia. AD - Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia. AD - Brain & Mind Centre, The University of Sydney, Sydney, New South Wales, Australia. AD - Woolcock Institute of Medical Research, Centre for Sleep and Chronobiology, University of Sydney, Sydney, New South Wales, Australia. FAU - Comas, Maria AU - Comas M AD - Woolcock Institute of Medical Research, Centre for Sleep and Chronobiology, University of Sydney, Sydney, New South Wales, Australia. FAU - Raisin, Isabelle AU - Raisin I AD - University Library, The University of Sydney, Sydney, New South Wales, Australia. FAU - Saini, Bandana AU - Saini B AD - Woolcock Institute of Medical Research, Centre for Sleep and Chronobiology, University of Sydney, Sydney, New South Wales, Australia. AD - Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia. FAU - Gordon, Christopher J AU - Gordon CJ AD - Woolcock Institute of Medical Research, Centre for Sleep and Chronobiology, University of Sydney, Sydney, New South Wales, Australia. AD - Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia. FAU - McKinnon, Andrew C AU - McKinnon AC AD - Healthy Brain Ageing Program, Faculty of Science, School of Psychology, The University of Sydney, Sydney, New South Wales, Australia. AD - Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia. AD - Brain & Mind Centre, The University of Sydney, Sydney, New South Wales, Australia. FAU - Naismith, Sharon L AU - Naismith SL AD - Healthy Brain Ageing Program, Faculty of Science, School of Psychology, The University of Sydney, Sydney, New South Wales, Australia. AD - Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia. AD - Brain & Mind Centre, The University of Sydney, Sydney, New South Wales, Australia. FAU - Marshall, Nathaniel S AU - Marshall NS AD - Woolcock Institute of Medical Research, Centre for Sleep and Chronobiology, University of Sydney, Sydney, New South Wales, Australia. AD - Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia. FAU - Grunstein, Ronald R AU - Grunstein RR AD - Woolcock Institute of Medical Research, Centre for Sleep and Chronobiology, University of Sydney, Sydney, New South Wales, Australia. AD - Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales, Australia. AD - Royal Prince Alfred Hospital, Sydney, New South Wales, Australia. FAU - Hoyos, Camilla M AU - Hoyos CM AUID- ORCID: 0000-0002-6543-4016 AD - Healthy Brain Ageing Program, Faculty of Science, School of Psychology, The University of Sydney, Sydney, New South Wales, Australia. AD - Charles Perkins Centre, The University of Sydney, Sydney, New South Wales, Australia. AD - Brain & Mind Centre, The University of Sydney, Sydney, New South Wales, Australia. AD - Woolcock Institute of Medical Research, Centre for Sleep and Chronobiology, University of Sydney, Sydney, New South Wales, Australia. LA - eng GR - National Health and Medical Research Council/ GR - CogSleep CRE/ GR - University of Sydney/ PT - Journal Article PT - Meta-Analysis PT - Review PT - Systematic Review DEP - 20211230 PL - England TA - J Pineal Res JT - Journal of pineal research JID - 8504412 RN - JL5DK93RCL (Melatonin) SB - IM MH - Adult MH - *COVID-19 MH - Humans MH - *Melatonin/pharmacology MH - SARS-CoV-2 MH - Sleep OTO - NOTNLM OT - dementia OT - drug-related side effects and adverse reactions OT - melatonin OT - meta-analysis OT - preventative medicine OT - safety EDAT- 2021/12/20 06:00 MHDA- 2022/02/19 06:00 CRDT- 2021/12/19 21:12 PHST- 2021/12/14 00:00 [revised] PHST- 2021/11/05 00:00 [received] PHST- 2021/12/14 00:00 [accepted] PHST- 2021/12/20 06:00 [pubmed] PHST- 2022/02/19 06:00 [medline] PHST- 2021/12/19 21:12 [entrez] AID - 10.1111/jpi.12782 [doi] PST - ppublish SO - J Pineal Res. 2022 Mar;72(2):e12782. doi: 10.1111/jpi.12782. Epub 2021 Dec 30.