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, 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 the Downs and Black checklist.
Nine studies measured melatonin or melatonin metabolites in ASD 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 ASD. Six studies reported improved daytime behavior with melatonin
use. Eighteen studies on melatonin treatment in ASD were identified; these studies
reported improvements in sleep duration, sleep onset latency, and night-time awakenings.
Five of these studies were randomized double-blind, placebo-controlled crossover studies;
two of the studies contained blended samples of children with ASD and other developmental
disorders, but only data for children with ASD 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 Δ 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 Δ 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 Δ-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 Δ-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 ASD 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.
© The Authors. Developmental Medicine & Child Neurology © 2011 Mac Keith Press.