Long-Term Efficacy and Safety of Pediatric Prolonged-Release Melatonin for Insomnia in Children with Autism Spectrum Disorder

Oral Presentation
Saturday, May 12, 2018: 1:45 PM
Arcadis Zaal (de Doelen ICC Rotterdam)
A. Maras1, B. A. Malow2, T. Nir3, N. Zisapel3 and P. Gringras4, (1)Yulius Academy, Yulius Mental Health Organization, Barendrecht, Netherlands, (2)Sleep Disorders Division, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, (3)Neurim Pharmaceuticals, Tel Aviv, Israel, (4)Children's Sleep Medicine, Evelina London Children's Hospital, Guy's and St Thomas', London, United Kingdom
Background: A recent double-blind randomized placebo-controlled study demonstrated 3-months' efficacy and safety of novel pediatric-appropriate prolonged-release melatonin minitablets (PedPRM; 2/5 mg) vs. placebo in children and adolescents with Autism Spectrum (ASD) and Neurogenetic Disorders (NGD) suffering from insomnia.

Objectives: To investigate the long term maintenance of PedPRM efficacy, safety and dosing in patients receiving 1 year of study medication.

Methods: A prospective 9-months open-label follow up study of efficacy and safety of PedPRM in community dwelling patients with ADS/NGD. Sleep measures included the validated caregivers’ Sleep and Nap Diary (SND) and Composite Sleep Disturbance Index (CSDI).


95 patients aged 2-17.5 years [mean age 9 ± 4.24, 74.7% males] who completed the 3 months double-blind trial (51 from PedPRM arm and 44 from the placebo arm) received open-label PedPRM at final 2/5 mg dose with optional dose adjustment to 2-10 mg/day after 3 months. By the end of the follow up period, 41 of the PedPRM randomized group completed 1 year of PedPRM and 38 of the placebo randomized group completed 9 months of PedPRM. The improvements in total sleep time (TST), sleep latency (SL) and duration of uninterrupted sleep (longest sleep episode) seen in the double blind-phase were maintained throughout the follow up period with mean improvement of 44.35 minutes in TST(p=0.002), -41.36 minutes in SL (p<0.001) and 78.63 minutes in uninterrupted sleep (p<0.001) over baseline. In addition, CSDI measured sleep disturbance and parent satisfaction of their child's sleep patterns, were significantly improved (p<0.001 for both). There was no evidence of tolerance to PedPRM. Overall 75% of patients in the 9 months follow up had clinically relevant improvement in TST of 45 minutes or more, or reduction in sleep latency of 15 minutes or more, or both, compared to 69% by the end of the DB phase. Of the 71 completers who provided SND data, 53 (75%) achieved an overall improvement of one hour or more in TST, SL or both, over baseline. The average daily dose was 5.3 mg (range 2-10 mg). PedPRM was generally safe; daytime somnolence was more commonly reported treatment-related adverse event, with PedPRM than placebo.


PedPRM is an effective and safe treatment option for long term treatment of children with ASD suffering from insomnia.