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Melatonin in autism spectrum disorders: A systematic review and meta-analysis – Source: Developmental Medicine and Child Neurology, Apr 19, 2011

  [ 12 votes ]   [ Discuss This Article ]
By Daniel A Rossignol, Richard E Frye • • April 28, 2011

Aim: The aim of this study was to investigate melatonin-related findings in autism spectrum disorders (ASD), including autistic disorder, Asperger syndrome, Rett syndrome, and pervasive developmental disorders, not otherwise specified.

Comprehensive searches were conducted in the PubMed, Google Scholar,?Method CINAHL, EMBASE, Scopus, and ERIC databases from their inception to October 2010. Two reviewers independently assessed 35 studies that met the inclusion criteria. Of these, meta-analysis was performed on five randomized double-blind, placebo-controlled studies, and the quality of these trials was assessed using ?using the Downs and Black checklist.


• Nine studies measured melatonin or?melatonin metabolites in autism spectrum disorders, and all reported at least one abnormality, including:

- An abnormal melatonin circadian rhythm in four studies,

- Below average physiological levels of melatonin and/or melatonin derivates in seven studies,

- And a positive correlation between these levels and autistic behaviors in four studies.

• Five studies reported gene abnormalities that could contribute to decreased melatonin production or adversely affect melatonin receptor function in a small percentage of children with autism spectrum disorders.

• Six studies reported improved daytime behavior with melatonin use.

• Eighteen studies on melatonin treatment in autism spectrum disorders were identified; these studies reported improvements in sleep duration, sleep onset latency, and night-time awakenings.

Five of these studies [on melatonin treatment] were randomized double-blind, placebo-controlled crossover studies; two of the studies contained blended samples of children with autism spectrum disorders and other developmental disorders, but only data for children with autism spectrum disorders were used in the meta-analysis.

The meta-analysis found significant improvements with large effect sizes in:

Sleep duration (73 min compared with baseline, Hedge's g 1.97 [95% confidence interval {CI} CI 1.10-2.84], Glass's ? 1.54 [95% CI 0.64-2.44]; 44 min compared with placebo, Hedge's g 1.07 [95% CI 0.49-1.65], Glass's ? 0.93 [95% CI 0.33-1.53])

• And sleep onset latency (66 min compared with baseline, Hedge's g-2.42 [95% CI -1.67 to -3.17], Glass's ?-2.18 [95% CI -1.58 to -2.76]; 39 min compared with placebo, Hedge's g-2.46 [95% CI -1.96 to -2.98], Glass's ?-1.28 [95% CI -0.67 to -1.89])

• But not in night-time awakenings.

The effect size varied significantly across studies but funnel plots did not indicate publication bias.

The reported side effects of melatonin were minimal to none.

Some studies were affected by limitations, including small sample sizes and variability in the protocols that measured changes in sleep parameters. 


Melatonin administration in autism spectrum disorders is associated with improved sleep parameters, better daytime behavior, and minimal side effects.

Additional studies of melatonin would be helpful to confirm and expand on these findings.

Source: Developmental Medicine and Child Neurology, Apr 19, 2011. PMID: 21518346, by Rossignol DA, Frye RE. International Child Development Resource Center, Melbourne, Florida; Division of Child and Adolescent Neurology and Children's Learning Institute, Department of Pediatrics, University of Texas Health Science Center at Houston, Texas, USA. [Email:]

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