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