Main idea: Long-term melatonin treatment in combination with adequate sleep hygiene interventions may give clinical benefits to children with neurodevelopmental disorders and potentially elevates their well-being.
Clinical evidence on the long-term efficacy and safety of melatonin treatment for sleep problems in children with neurodevelopmental disorders (NDDs) who underwent adequate sleep hygiene interventions is required.
Methods: 26-week multi center collaborative uncontrolled open-label phase III clinical trial of melatonin granules in children 6 to 15 years of age who had NDDs and sleep problems was conducted.
Results: Between June 2016 and July 2018, 99 children (80 males and 19 females, 10.4 years in mean age) were enrolled at 17 medical institutions in Japan-74, 60, 22, 9, 6, and 1 of whom had autism spectrum disorder, attention-deficit/hyperactivity disorder, intellectual disabilities, motor disorders, specific learning disorder, and communication disorders, respectively, at baseline. Fifteen children received the maximum dose of 4 mg among the prespecified dose levels. SOL recorded with the electronic sleep diary shortened significantly in the medication phase I from baseline, and the SOL-shortening effect of melatonin persisted in the medication phase II and the follow-up phase. Temper upon wakening and sleepiness after awakening improved significantly in the medication phase I from baseline and persisted in the follow-up phase. The following subscales of the ABC-J improved significantly: stereotypic behavior in the medication phase I; and irritability, hyperactivity, and inappropriate speech in the medication phase II. Treatment-emergent adverse events did not occur 16 weeks after medication onset, and NDDs did not deteriorate in the follow-up phase.