Pediatric Prolonged-Release Melatonin for Sleep in Children with Autism Spectrum Disorder: Impact on Child Behavior and Caregiver's Quality of Life

J Autism Dev Disord. 2019 Aug;49(8):3218-3230. doi: 10.1007/s10803-019-04046-5.


A randomized, 13-weeks, placebo-controlled double-blind study in 125 subjects aged 2-17.5 years with Autism Spectrum Disorder or Smith-Magenis syndrome and insomnia demonstrated efficacy and safety of easily-swallowed prolonged-release melatonin mini-tablets (PedPRM; 2-5 mg) in improving sleep duration and onset. Treatment effects on child behavior and caregiver's quality of life were evaluated. PedPRM treatment resulted in significant improvement in externalizing but not internalizing behavior (Strengths and Difficulties questionnaire; SDQ) compared to placebo (p = 0.021) with clinically-relevant improvements in 53.7% of PedPRM-treated versus 27.6% of placebo-treated subjects (p = 0.008). Caregivers' quality of life also improved with PedPRM versus placebo (p = 0.010) and correlated with the change in total SDQ (p = 0.0005). PedPRM alleviates insomnia-related difficulties, particularly externalizing behavior in the children, subsequently improving caregivers' quality of life.

Keywords: Autism; Behavior; Children (pediatric); Prolonged-release melatonin; Sleep.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Autism Spectrum Disorder / drug therapy*
  • Caregivers*
  • Central Nervous System Depressants / administration & dosage
  • Central Nervous System Depressants / pharmacology
  • Central Nervous System Depressants / therapeutic use*
  • Child
  • Child Behavior / drug effects*
  • Child, Preschool
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Melatonin / administration & dosage
  • Melatonin / pharmacology
  • Melatonin / therapeutic use*
  • Quality of Life*
  • Sleep / drug effects*


  • Central Nervous System Depressants
  • Melatonin