Optimizing timing and dose of exogenous melatonin administration in neuropsychiatric pediatric populations: a meta-analysis on sleep outcomes

Melatonin is known to be effective in improving sleep in pediatric patients affected by neurological and psychiatric conditions. However, no guidelines exist advising the most effective treatment schedule. This systematic review and meta-analysis aimed to identify the dose, time of administration and treatment duration associated with the maximal treatment efficacy. The systematic search, conducted across multiple databases following PRISMA guidelines and including studies published up to April 30, 2024, yielded 21 studies. Mean differences in sleep-related variables between the treatment and the placebo group were considered as study outcomes. Dose-response curves and meta-regression models were fitted to test the effect of treatment-related parameters. Melatonin significantly reduced Sleep onset latency and increased Sleep efficiency and Total sleep time. Sleep onset latency reduction was associated with an advancement in the time between administration with respect to bedtime, while increased Sleep efficiency and Total sleep time with longer treatment durations. Melatonin reached the maximal efficacy between 2 and 4 mg/day. Our results suggest a dose and time of administration that may enhance melatonin's sleep promoting effects (2–4 mg, 3 h before bedtime) and, if replicated by large clinical trials, could guide clinical practice in managing sleep disturbances in children experiencing neuropsychiatric conditions.