Melatonin in children

Short answer

The evidence for melatonin in children largely concerns insomnia in children with neurodevelopmental disorders (such as autism spectrum disorder and ADHD) in whom behavioral measures have not worked; one meta-analysis reported an increase of about 48 minutes in total sleep time and a shortening of about 29 minutes in sleep onset. Long-term safety, particularly pubertal development, is not well documented, and use is a physician decision. ^{[2] [5]}

In which situations has melatonin been studied in children?

The strongest data for melatonin in children come from insomnia in children with neurodevelopmental disorders. The systematic review by Abdelgadir and colleagues covered 13 randomized trials (682 children) comparing melatonin with placebo or another intervention in children under 18 with neurodevelopmental disorders. In the meta-analysis of nine studies (541 children), total sleep time increased by 48.26 minutes compared with placebo (95% CI 36.78–59.73); in 11 studies (581 children), sleep onset time shortened by 28.97 minutes; there was no difference in the frequency of night waking. No serious melatonin-related side effects were reported; the authors state that the quality of the evidence is limited because of heterogeneity and inconsistency between studies. ^[2]

According to the recommendations of an expert conference held in Rome in 2014 (Bruni et al.), the best evidence is for difficulty falling asleep and delayed sleep phase; melatonin reduces sleep onset time and increases total sleep time, but does not reduce night awakenings. The same review states that many children with developmental disorders such as autism, ADHD and intellectual disability may benefit from melatonin for their sleep problems, and notes that there is no evidence that the prolonged-release form is superior to the immediate-release form. ^[3]

What are the details of the randomized trial?

The double-blind, placebo-controlled study by Gringras and colleagues covered 125 children aged 2–17.5 years whose sleep did not improve despite behavioral measures (96.8% autism spectrum disorder, 3.2% Smith-Magenis syndrome); pediatric prolonged-release melatonin minitablets (increased from 2 mg to 5 mg) or placebo were given for 13 weeks. According to the parent diary, the primary endpoint total sleep time increased by a mean of 57.5 minutes in the melatonin group and 9.14 minutes in the placebo group (adjusted difference 32.43 minutes; p = 0.034); sleep onset time shortened by 39.6 minutes with melatonin and 12.5 minutes with placebo (adjusted difference 25.30 minutes; p = 0.011). The clinically meaningful response rate was 68.9% versus 39.3% (NNT 3.38). Somnolence was reported more often in the melatonin group. ^[1]

On its summary page, the EMA describes the same study as 125 patients, 121 with autism and four with Smith-Magenis syndrome, and states that all patients had previously tried measures such as a regular sleep routine; it reports that at 13 weeks those taking melatonin slept a mean of 51 minutes longer per night and those taking placebo 19 minutes longer, and that those taking melatonin fell asleep about 38 minutes earlier and those taking placebo 13 minutes earlier. The two sources report the figures differently; both are given as cited. ^[4]

Two of the five authors reported an affiliation with the pharmaceutical company that developed the product; the PubMed abstract contains no separate funding statement. ^[1]

Behavioral measures first?

For the pediatric product in Europe, the EMA summary states that the medicine is used when other measures such as a regular sleep routine have not worked; the indication is children and adolescents aged 2–18 years with autism spectrum disorder and/or neurogenetic disorders and children and adolescents aged 6–17 years with ADHD; it states that treatment should be reviewed by the physician at least every 6 months and continued only if there is benefit; the medicine is dispensed by prescription only. ^[4] The Gringras study also covered children whose sleep did not improve despite behavioral measures. ^[1] These two documents show that melatonin was studied and approved for situations that do not respond to behavioral measures.

Safety in children: what is known?

Long-term open-label follow-up: Maras and colleagues followed 95 children who had completed the 13-week double-blind study for a further 39 weeks (with 2, 5 or 10 mg daily). After 52 weeks of continuous treatment compared with baseline, sleep in the melatonin group lengthened by 62.08 minutes and sleep onset shortened by 48.6 minutes; in 55/72 of completers (76%), total sleep time, sleep onset time or both improved by at least 1 hour. The most common treatment-related side effects were fatigue (5.3%) and mood swings (3.2%). The study is open-label and uncontrolled; the placebo comparison covers only the first 13 weeks. Three of the nine authors of this follow-up study also have an affiliation with the company that developed the product. ^[6]

Critical view (2015): Kennaway emphasizes that, although melatonin was being prescribed to children increasingly often, at that time it was not licensed for use in children anywhere in the world, had not passed the formal safety testing expected for a new drug (particularly long-term safety in children), had marked effects on the reproductive system in rodents, sheep and primates, and could interact with some drugs commonly used in children. This assessment dates from 2015; the EMA subsequently approved a pediatric product (section above). ^[5]

Seizures: the two documents differ. The Rome conference recommendations state that animal studies and limited human data suggest melatonin does not worsen seizures and may even reduce them; the Turkish SmPC, on the other hand, states that melatonin may increase seizure frequency in people who have seizures and may trigger the development of seizures in children and adolescents with multiple neurological deficits. The two should be read side by side; in a child with a seizure history, the decision rests with the physician. ^{[3] [9]}

Metabolism: The Rome recommendations state that reduced CYP1A2 activity (genetic or due to a concomitant drug) may slow melatonin metabolism and lead to loss of effect, and that reducing the dose may correct this. ^[3]

What is known about pubertal development?

This question is a theoretical concern and the data are limited. The SmPC of a melatonin tablet licensed in Türkiye states that the safety profile in children and adolescents, particularly with long-term use, has not been fully established and that long-term use may adversely affect blood glucose control, pubertal development and sexual maturation. ^[9]

Direct human data are limited. Zwart and colleagues administered an online survey to young adults who had started melatonin in prepubertal childhood because of chronic difficulty falling asleep; the response rate was 47.8%. Those still using melatonin at the time of the survey were 27.3% (mean treatment duration 10.8 years); the overall mean treatment duration was 7.1 years. Sleep quality did not differ from control groups and side effects were few; however, perceived pubertal timing suggested a tendency toward delay in former and current melatonin users. The authors state that the study has low power because of its small sample size, that sleep timing was based on self-report and that the control groups were mostly students. ^[7]

That is, the observation gave a signal that “puberty may be delayed” but is not a design that can show causality and does not prove the opposite either. This result can be considered neither reassuring nor alarming; the uncertainty should be left as it is.

Accidental ingestion in children

In the analysis by Lelak and colleagues, 260,435 isolated melatonin exposures in people aged 19 and under were reported to US poison control centers between 2012 and 2021; the annual number increased by 530%. Of the exposures, 83.8% were in children aged 5 and under and 94.3% were unintentional. Of 27,795 cases managed at a health care facility, 4,097 (14.7%) were hospitalized; 287 were admitted to intensive care; five children required mechanical ventilation and two deaths were reported (the relation of the deaths to melatonin was classified as “unknown” in the system). Most children had no effect (30.1%) or a minor effect (67.8%). ^[8]

The MMWR erratum of July 8, 2022 corrected the proportion without symptoms and some rows in the table; the numbers in the corrected table are used here. Because melatonin is regulated as a supplement in the US, these data cannot be applied directly to the context of licensed medicines in Türkiye; they show the risk of accidental ingestion for any medicine kept where children can reach it. ^[8]

What is the status of melatonin for children in Türkiye?

• As a supplement: Melatonin was not found suitable for use in food supplements in the Ministry of Agriculture and Forestry list; according to the TİTCK (Turkish Medicines and Medical Devices Agency) letter dated September 2, 2025, products containing melatonin are evaluated as human medicinal products and, from June 9, 2025, no food supplement containing melatonin may be sold; according to the provincial health directorate that forwarded the letter, products containing melatonin may be sold only with TİTCK authorization/license and from pharmacies and pharmaceutical warehouses. ^[10]
• Licensed product examined: The approved indication in the SmPC (Turkish KÜB) of the 3 mg tablet licensed in Türkiye is short-term jet lag in adults; the document states that safety and efficacy for jet lag have not been established in children and adolescents under 18 and that, because of insufficient data, it should not be used at ages 0–18. ^[9]

This guide does not assess whether other licensed products with pediatric indications exist in Türkiye and does not describe ways of obtaining melatonin for a child. For a child’s sleep problem, the decision is made on the physician’s assessment.

Detailed guideMelatonin: overview, status in Türkiye and evidence summary→ Detailed guideMelatonin benefits: which claims are supported?→ Detailed guideMelatonin harms and side effects→ Detailed guideWhen is melatonin taken?→

This guide does not recommend personal doses; study doses only describe study conditions.