Sleep problems, generally defined as difficulty initiating and/or maintaining sleep, are one of the most common comorbid conditions experienced by individuals with autism spectrum disorder (ASD). Disrupted sleep worsens child's social interaction, day to day life, academic achievement, and correlates with increased maternal distress and parental sleep disruption.

Bedtime routines and sleep hygiene is the mainstay of sleep management. If that fails, it should be combined with pharmacologic intervention but little evidence-based data exist to support such approach. To date, there are no approved medications to treat insomnia in pediatric patients, including ASD. Sleep medications are prescribed off-label although none was proven effective and safe in this population, leaving many families desperate for a better solution.

The normal sleep–wake cycle is governed by the circadian clock residing in the hypothalamus. The clock is tuned by light and by its downstream signal of darkness hormone- melatonin. Mutations in genes involved in clock and melatonin pathways and low melatonin levels have been found in individuals with ASD, which may explain problems with sleep initiation and maintenance and/or early waking.

Whereas a placebo-controlled randomized clinical trial (RCT) indicated that normal-release melatonin improves only sleep latency in children with neurodevelopmental disorders including ASD, a recently completed long-term placebo-controlled RCT indicated that prolonged-release melatonin (PRM) minitablets effectively improved both sleep latency and total sleep time (TST) in children with ASD.

Behavioral treatment strategies along with PRM pharmacotherapy can help improve the quality of life of ASD children and decrease the family and parental distress.