Safety of higher doses of melatonin in adults: A systematic review and meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 34923676 · doi:10.1111/jpi.12782
What was done
Authors systematically reviewed randomized controlled trials investigating high-dose melatonin (≥10 mg) in adults over 30 years across multiple databases through October 2020. Risk of bias was evaluated, and outcomes—adverse events (AEs), serious adverse events (SAEs), and AE-related withdrawals—were pooled using random-effects meta-analyses.
What was found
A total of 79 trials (3,861 participants) were identified, but 29 studies (37%) failed to mention whether adverse events occurred. Only 4 trials met criteria for low risk of bias and were included in the meta-analysis. In these 4 studies, melatonin showed no statistically significant difference compared to controls for SAEs (Rate Ratio = 0.88, 95% CI [0.52, 1.50], p = .64) or withdrawals due to AEs (Rate Ratio = 0.93, 95% CI [0.24, 3.56], p = .92). However, melatonin significantly increased overall AEs, primarily drowsiness, headache, and dizziness (Rate Ratio = 1.40, 95% CI [1.15, 1.69], p < .001).
Why it matters
High-dose melatonin appears to have an acceptable safety profile without an observed rise in serious adverse events, though patients should be counseled on common mild effects like sedation and dizziness.
Limits
The meta-analysis was constrained to only 4 low-risk-of-bias studies, leading to very wide confidence intervals. Over a third of published high-dose melatonin trials omitted safety and AE data entirely, and the review was limited to adults over 30 years old.
Cited by
- contradicts Vivid or bizarre dreams are the primary side effect associated with high doses or overdosing of melatonin.