Melatonin is the most common substance involved in overdoses and unsupervised medication ingestions among children aged 0-5 years presenting to emergency departments in the U.S. These cases increased nearly fivefold between 2009 and 2021. However, most children experience only minor side effects, whereas some cases have led to more severe adverse outcomes or death. Generally, melatonin is recommended after behavioral interventions for sleep disturbances among children with autism, at doses ranging from 1 to 10 mg. In typically developing children, melatonin should be used only for a short time and under medical supervision. However, concerns remain regarding hormonal effects and prolonged use, as well as long-term safety in early childhood. Hence, more research is needed to understand better the long-term efficacy and safety of melatonin in young children. These issues were comprehensively addressed in a recent systematic review published in JAMA Network Open.
This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and was registered with the International Prospective Register of Systematic Reviews (PROSPERO, CRD42025645422). A comprehensive literature search was conducted across nine databases, such as Ovid Medline, Web of Science, CINAHL, APA PsycInfo, Embase, Alt HealthWatch, Cochrane CENTRAL, International Clinical Trials Registry Platform, and ClinicalTrials.gov. The search covered studies from database inception through February 26, 2025, without restrictions on publication year. Both interventional and observational studies assessing melatonin use for sleep in young children were included. Study quality was examined through the Black and Downs Checklist.
A total of 19 studies met the inclusion criteria, including 12 observational studies, six completed clinical trials, and one clinical trial protocol. Â Approximately 245 young children with autism spectrum disorders were involved in six complete trials with a mean study duration of 12.7 weeks. No trials included typically developing children. Observational studies used poisoning and registry data from the U.S., Australia, and Europe, covering up to 21 years and largely involving general pediatric populations.
Eight observational studies reported that the long-term safety of melatonin was related to melatonin prescribing among young children. Prescribing rates increased over time in five studies with reported rises of up to 500%. Whereas, defined daily doses of 2 mg doubled in Sweden but remained stable in Norway. Across four studies, extended melatonin use persisted in approximately 40%-50% of children at 2-3 years of follow-up, although rates were as low as 10% in some populations. Children with autism spectrum disorder showed slightly higher long-term use (46.4%) compared to the entire population (40%) in Denmark-based studies. Â
Three studies reported sharp increases in melatonin-related poisoning or emergency department visits from 2018 to 2022, most commonly due to unsupervised ingestion, with 89-90% involving melatonin alone. Across six trials (245 participants) of children with autism, adverse events were mostly mild or absent. Behavioral outcomes showed reductions in sleep onset latency and increases in total sleep time of nearly one hour in several trials, although benefits diminished after discontinuation. Limited evidence suggested no clear long-term effects on growth or pubertal development. Study quality varied: trials were rated good, fair, or poor, limited by power and validity. Observational studies were mostly fair, with stronger external validity but weaker internal validity.
This review was limited by small pediatric sample sizes, limited assessment of long-term health outcomes, restricted generalizability, inadequate power and confounding control, and variable and relatively short trial durations.
In conclusion, this review demonstrates that rising melatonin use, prolonged exposure, and increasing adverse events are associated with young children. While melatonin may improve sleep outcomes in certain populations, both short- and long-term safety data remain limited. These findings underscore the need for cautious prescribing practices and further high-quality research to establish the long-term safety of melatonin use in early childhood.
Reference: Kracht CL, Bolamperti G, Breeden R, et al. Melatonin Use in Young Children: A Systematic Review. JAMA Netw Open. 2026;9(1):e2551958. doi:10.1001/jamanetworkopen.2025.51958
