Safety of higher doses of melatonin in adults: A systematic review and meta-analysis.
Study Goal
The researchers aimed to investigate the safety of higher doses of melatonin (≥10 mg) in adults, particularly focusing on adverse events, serious adverse events, and withdrawals due to adverse events.
Results Summary
The meta-analysis found no detectable increase in serious adverse events or withdrawals due to adverse events with high-dose melatonin, but it did show an increased risk of minor adverse effects like drowsiness, headache, and dizziness. Overall, melatonin appeared to have a good safety profile, though limited reporting and wide confidence intervals suggest the need for better long-term safety data.
Population
Human adults over 30 years of age with various medical conditions.
Effective Dosage
≥10 mg (high-dose melatonin)
Duration
Not specified in the abstract
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
high-dose melatonin (≥10 mg) | no change | serious adverse events (SAEs) | human adults over 30 years of age | Rate Ratio = 0.88 [0.52, 1.50], p = .64 | did not cause a detectable increase | #1 |
high-dose melatonin (≥10 mg) | no change | withdrawals due to AEs | human adults over 30 years of age | 0.93 [0.24, 3.56], p = .92 | did not cause a detectable increase | #2 |
high-dose melatonin (≥10 mg) | increase | AEs such as drowsiness, headache and dizziness | human adults over 30 years of age | 1.40 [1.15, 1.69], p < .001 | did appear to increase the risk | #3 |
melatonin | neutral | a good safety profile | human adults over 30 years of age | - | appears to have | #4 |
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.