A quarterly publication of the Autism Research Institute

The Autism Research Review International is quarterly publication of the Autism Research Institute

Spring, 2021 | Number 2, Volume 35

Time-release melatonin effective in improving sleep in children with ASD, does not alter puberty

A new study, in addition to adding to evidence that time-release melatonin may improve sleep in individuals with autism, indicates that administering the hormone does not have any adverse effect on development during puberty. 

An earlier double-blind, placebo-controlled study by Paul Gringras and colleagues (see ARRI 2018, Volume 2) involved 119 children between 2 and 17 years of age. The children’s parents first received instruction on behavioral interventions to improve their children’s sleep. Children who did not respond to these interventions then received prolonged-release melatonin, in doses beginning at 2 mg per day and increasing to 5 mg if needed, for 13 weeks. At the end of the study, the researchers reported, 68.9% of children taking melatonin slept better, compared to only 39.3% of children taking the placebo. 

In the new study by Gringras and colleagues (including lead author Beth Malow), 80 children from the original study continued to take time-release melatonin for an additional 91 weeks, for a total of two years. Dosages were increased as needed, up to 10 mg. 

The researchers report, “Improvements in child sleep disturbance and caregiver satisfaction with child sleep patterns, quality of sleep, and quality of life were maintained throughout the 104-week treatment period.” Moreover, while concerns have been raised about the possible effects of supplemental melatonin on puberty (because melatonin levels typically drop during puberty), the researchers say, “Changes in mean weight, height, body mass index, and pubertal status… were within normal ranges for age with no evidence of delay in body mass index or pubertal development.” Adverse effects, including sleepiness, fatigue, and mood swings, were few and generally mild, and no withdrawal symptoms were seen during a two-week washout period. 

The researchers conclude, “Nightly doses [of time-release melatonin] at optimal dose (2, 5, or 10 mg nightly) is safe and effective for long-term treatment in children and adolescents with autism spectrum disorder and insomnia.” They caution, however, that unlike their original study, this study was open-label, with no children receiving a placebo.

Malow and colleagues say they detected no effects on puberty in children taking extended-release melatonin for two years.


“Sleep, growth, and puberty after 2 years of prolonged-release melatonin in children with autism spectrum disorder,” Beth A. Malow, Robert L. Findling, Carmen M. Schroder, Athanasios Maras, John Breddy, Tali Nir, Nava Zisapel, and Paul Gringras, Journal of the American Academy of Child & Adolescent Psychiatry, Vol. 60, No. 2, February 2021, 252-261. Address: Beth Malow, Sleep Division, Department of Neurology, Vanderbilt University Medical Center, 1161 21st Avenue South, Room A-0116, Nashville, TN 37232, [email protected].