Abstract
IMPORTANCE: Melatonin is the leading cause of unsupervised medication exposure and overdose in emergency departments for young children (aged 0-6 years). Existing literature has documented the benefits of melatonin in older children (aged 7-18 years) with neurologic conditions but has yet to examine young children. OBJECTIVE: To examine the long-term outcomes (safety and effectiveness) associated with melatonin use in young children. EVIDENCE REVIEW: Nine databases, including Ovid MEDLINE, Embase, and Web of Science; 2 clinical trial registries; existing subject matter systematic reviews; and forward and backward citation of included articles were reviewed from inception to February 26, 2025, to identify observational and interventional studies that investigated the safety and effectiveness of exogenous melatonin on sleep in young children. Methodological quality was assessed using the Downs and Black Checklist. FINDINGS: Nineteen articles representing 12 observational studies, 6 experimental studies (hereafter, trials), and 1 protocol published between 2000 and 2025 were included. The observational studies reported on 9 years (range, 3-21 years) of data from Nordic or Australian registries or poisoning data from the US and Portugal. The trials included 167 young children with neurologic conditions and lasted a mean of 12.7 weeks (range, 2 weeks to 2 years). For safety, observational studies documented rises in prescribing practices, extended use, and overdoses, especially in the past decade. For effectiveness, trials provided evidence for improved sleep onset in young children with neurologic conditions (eg, autism spectrum disorder), with few adverse events. However, data regarding long-term outcomes for other behaviors and health outcomes were absent, and efficacy data were not available for children with typical development. The methodological quality of included studies was poor for 3 studies, fair for 9, and good for 6. CONCLUSIONS AND RELEVANCE: These findings suggest a global rise in prescriptions without efficacy data on use in children with typical development, underscoring the need to identify strategies to prevent and reduce melatonin use in young children, as well as to improve adherence by pediatricians to evidence-based practice standards.