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Abstract
Melatonin is an endogenous neurohormone produced predominantly in the pineal gland.
Recent studies have implicated abnormalities in melatonin physiology and the circadian
rhythm in individuals with autism spectrum disorders (ASD). These physiological abnormalities
include lower nighttime melatonin or melatonin metabolite concentrations in ASD compared
to controls. These abnormalities in melatonin concentrations may be directly attributed
to variations in melatonin pathway physiology as both functional and genetic variations
in this pathway have been reported in children with ASD. Four studies have observed
a correlation between abnormal melatonin concentrations and the severity of autistic
behaviors. Twenty clinical studies have reported improvements in sleep parameters
with exogenous melatonin supplementation in ASD, including longer sleep duration,
less nighttime awakenings and quicker sleep onset. A recent meta-analysis of five
randomized, double-blind, placebo-controlled crossover trials examining exogenous
melatonin supplementation in ASD reported significant improvements with large effect
sizes in total sleep duration and sleep onset latency compared to both baseline and
placebo. Six studies reported that the nighttime administration of exogenous melatonin
was associated with better daytime behaviors. Four studies reported improvements with
exogenous melatonin supplementation when other sleep medications had previously failed.
Adverse effects of melatonin were minimal to none in the twenty treatment studies.
These studies indicate that the administration of exogenous melatonin for abnormal
sleep parameters in ASD is evidence-based. Further studies examining optimal effective
dosing and timing of dosing are warranted.