Optimizing the Time and Dose of Melatonin as a Sleep-Promoting Drug: A Systematic Review of Randomized Controlled Trials and Dose-Response Meta-Analysis.
Level 1 - systematic review of randomized trials
Systematic review and dose-response meta-analysis of randomized controlled trials
PubMed 38888087 · doi:10.1111/jpi.12985
What was done
A systematic review and dose-response meta-analysis of 26 double-blind, randomized controlled trials (published between 1987 and 2020, totaling 1,689 observations) evaluated the effect of exogenous melatonin versus placebo in healthy volunteers and patients with insomnia. The outcomes were standardized mean differences in sleep onset latency and total sleep time. Dose-response and meta-regression models assessed how dosage, time of administration relative to sleep, and time of day affected efficacy.
What was found
Melatonin progressively reduced sleep onset latency and increased total sleep time, peaking at 4 mg/day. Meta-regression models revealed that insomnia status (beta = 0.50, p < 0.001) and the time interval between administration and the sleep episode (beta = -0.16, p = 0.023) were significant predictors of sleep onset latency. Time of day (beta = -0.086, p < 0.01) was the only significant predictor of total sleep time. Results indicated that taking 4 mg/day 3 hours before bedtime was more effective than the common regimen of 2 mg 30 minutes before bedtime.
Why it matters
This review provides quantitative evidence that optimizing both timing (3 hours before sleep) and dose (4 mg/day) improves melatonin efficacy compared to typical clinical practice schedules.
Limits
The abstract pools healthy participants and individuals with insomnia, reports statistical regression coefficients rather than absolute minute changes in sleep metrics, and does not report data on adverse effects or formulation differences (such as immediate-release versus prolonged-release).