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J Am Acad Child Adolesc Psychiatry. 2020 Jan 23. pii: S0890-8567(20)30034-4. doi: 10.1016/j.jaac.2019.12.007. [Epub ahead of print]

Sleep, Growth, and Puberty After Two Years of Prolonged-Release Melatonin in Children With Autism Spectrum Disorder.

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Sleep Division, Vanderbilt University Medical Center, Nashville, TN. Electronic address:
Kennedy Krieger Institute/ Johns Hopkins University, Baltimore, MD.
Strasbourg University Hospital, France, and CNRS UPR 3212, Institute of Cellular and Integrative Neurosciences, Strasbourg, France.
Yulius Academy, Yulius Mental Health Organization, Dordrecht, The Netherlands.
Pharmastat Consulting Ltd, Canterbury, UK.
Neurim Pharmaceuticals Ltd, Tel Aviv, Israel.
Children's Sleep Medicine, Evelina London Children's Hospital, Guy's and St Thomas', London, UK.



A recent 3-month double-blind placebo-controlled study demonstrated efficacy and safety of child-appropriate prolonged-release melatonin (PedPRM) for insomnia in children with autism spectrum disorder (ASD). Here, we report on the long-term effects of PedPRM treatment on sleep, growth, body mass index, and pubertal development.


Eighty children and adolescents (96% ASD) ages 2-17.5 years who completed the double-blind placebo-controlled trial were given 2, 5 or 10 mg PedPRM nightly up to 104 weeks, followed by a 2 week placebo period to assess withdrawal effects.


Improvements in child sleep disturbance, and caregivers' satisfaction of their child's sleep patterns, quality of sleep and quality of life were maintained throughout the 104- week treatment period (p < 0.001 vs. baseline for all). During the 2-week withdrawal placebo period, measures declined as compared to the treatment period but were still improved compared to baseline. PedPRM was generally safe; the most frequent treatment-related adverse events (AE) were fatigue (6.3%), somnolence (6.3%), and mood swings (4.2%). The changes in mean weight, height, body mass index (BMI) and pubertal status (Tanner staging done by a physician) were within normal ranges for age with no evidence of delay in BMI or pubertal development.


Nightly PedPRM at optimal dose (2, 5, or 10 mg nightly) is safe and effective for long-term treatment in children and adolescents with ASD and insomnia. There were no observed detrimental effects on children's growth and pubertal development and no withdrawal or safety issues related to the use or discontinuation of the drug.


autism; melatonin; sleep

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