Prolonged-release melatonin (PedPRM) is safe and effective for children with autism spectrum disorder (ASD) who experience refractory insomnia, according to results from a randomized, double-blind, placebo-controlled trial published in the Journal of the American Academy of Child & Adolescent Psychiatry.
A total of 125 participants between 2 and 17.5 years of age were enrolled in the study. Patients whose sleep failed to improve with the use of behavioral intervention alone were randomly assigned to once-daily treatment with PedPRM 2 mg, escalated to 5 mg (n=60), or placebo (n=65) for 13 weeks. The participants included children with physician-diagnosed ASD, according to International Classification of Disease-10th Revision criteria, with or without attention-deficit/hyperactivity disorder and neurogenetic disorders. All of the participants had sleep issues. Sleep measures included the validated caregivers’ Sleep and Nap Diary (SND) and Composite Sleep Disturbance Index (CSDI). The primary end point was SND-reported total sleep time (TST) following 13 weeks of treatment.
At baseline, mean TST was 457.2 minutes in the PedPRM arm vs 459.9 minutes in the placebo arm. At the end of their 13-week treatment, PedPRM-treated patients slept an average of 57.5 minutes longer at night, compared with 9.14 minutes longer sleep among those who received placebo (P =.034).
Sleep latency decreased by an average of 39.6 minutes with PedPRM treatment vs 12.5 minutes with placebo (P =.011) and was not associated with an earlier wake up time. The rate of attaining a clinically meaningful response in TST and/or sleep latency was significantly higher in the PedPRM group vs the placebo group (68.9% vs 39.3%, respectively; P =.001), which translates into a corresponding number needed to treat of 3.38. Overall sleep disturbance, per CSDI, tended to decrease with PedPRM therapy.
The investigators noted that the mini-tablet formulation used in the study was highly acceptable among the pediatric patient population, many of whom often experience considerable difficulties swallowing. No unanticipated safety issues were observed, although somnolence, headache, and fatigue were reported more often among PedPRM-treated patients.
Gringras P, Nir T, Breddy J, Frydman-Marom A, Findling RL. Efficacy and safety of pediatric prolonged-release melatonin for insomnia in children with autism spectrum disorder [published online September 19, 2017]. J Am Acad Child Adolesc Psychiatry. doi:10.1016/j.jaac.2017.09.414