Optimizing the Time and Dose of Melatonin as a Sleep-Promoting Drug: A Systematic Review of Randomized Controlled Trials and Dose-Response Meta-Analysis.
Study Goal
The researchers aimed to evaluate the effects of exogenous melatonin on sleep-related parameters, focusing on optimal administration schedules and doses.
Results Summary
Melatonin reduced sleep onset latency and increased total sleep time, peaking at 4 mg/day. Optimal efficacy was achieved with administration 3 hours before bedtime.
Population
Patients with insomnia and healthy volunteers
Effective Dosage
Up to 4 mg/day
Duration
Not specified
Interactions
None mentioned
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
melatonin administration | decrease | sleep onset latency | patients with insomnia and healthy volunteers | - | gradually reduces | #1 |
melatonin administration | increase | total sleep time | patients with insomnia and healthy volunteers | - | increases | #2 |
melatonin administration | increase | sleep onset latency and total sleep time | - | 4 mg/day | peaking at | #3 |
melatonin administration | neutral | sleep onset latency | - | β = 0.50, p < 0.001 | significant predictors of | #4 |
melatonin administration | neutral | sleep onset latency | - | β = -0.16, p = 0.023 | significant predictors of | #5 |
melatonin administration | neutral | total sleep time | - | β = -0.086, p < 0.01 | significant predictor of | #6 |
advancing the timing of administration (3 h before the desired bedtime) and increasing the administered dose (4 mg/day) | increase | exogenous melatonin in promoting sleep | - | - | might optimize the efficacy of | #7 |
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 bedtime) and increasing the administered dose (4 mg/day), as compared to the exogenous melatonin schedule most used in clinical practice (2 mg 30 min before the desired bedtime), might optimize the efficacy of exogenous melatonin in promoting sleep.