Optimizing the Time and Dose of Melatonin as a Sleep‐Promoting Drug: A Systematic Review of Randomized Controlled Trials and Dose−Response Meta‐Analysis

作者：Francy Cruz‐Sanabria, Simone Bruno, Alessio Crippa, Paolo Frumento, Marco Scarselli, Debra J. Skene, Ugo Faraguna · 发表于：Journal of Pineal Research · 年份：2024 · DOI：10.1111/jpi.12985 · 被引用次数：57 · 研究领域：Sleep and related disorders、Sleep and Wakefulness Research、Circadian rhythm and melatonin

Previous studies have reported inconsistent results about exogenous melatonin's sleep-promoting effects. A possible explanation relies on the heterogeneity in administration schedule and dose, which might be accountable for differences in treatment efficacy. In this paper, we undertook a systematic review and meta-analysis of double-blind, randomized controlled trials performed on patients with insomnia and healthy volunteers, evaluating the effect of melatonin administration on sleep-related parameters. The standardized mean difference between treatment and placebo groups in terms of sleep onset latency and total sleep time were used as outcomes. Dose-response and meta-regression models were estimated to explore how time of administration, dose, and other treatment-related parameters might affect exogenous melatonin's efficacy. We included 26 randomized controlled trials published between 1987 and 2020, for a total of 1689 observations. Dose-response meta-analysis showed that melatonin gradually reduces sleep onset latency and increases total sleep time, peaking at 4 mg/day. Meta-regression models showed that insomnia status (β = 0.50, p < 0.001) and time between treatment administration and the sleep episode (β = -0.16, p = 0.023) were significant predictors of sleep onset latency, while the time of day (β = -0.086, p < 0.01) was the only significant predictor of total sleep time. Our results suggest that advancing the timing of administration (3 h before the desired bedtim...