Long-Term Efficacy and Safety of Pediatric Prolonged-Release Melatonin for Insomnia in Children with Autism Spectrum Disorder.
Level 3 - non-randomized controlled study
Prospective open-label extension study without a concurrent control group following a randomized trial
PubMed 30132686 · doi:10.1089/cap.2018.0020
What was done
A prospective, open-label follow-up evaluated the long-term efficacy and safety of pediatric prolonged-release melatonin (PedPRM, 2, 5, or 10 mg nightly) for 39 weeks in 95 children and adolescents (mean age 9 years, range 2–17.5) with autism spectrum disorder or neurogenetic disorders who completed an initial 13-week double-blind randomized controlled trial (51 initially randomized to PedPRM, 44 to placebo). Outcomes assessed via caregiver-reported sleep diaries, the Composite Sleep Disturbance Index (CSDI), Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale, and WHO-5 Well-Being Index.
What was found
After 52 weeks of continuous treatment in the group initially randomized to PedPRM, participants slept a mean of 62.08 minutes longer (p = 0.007), fell asleep 48.6 minutes faster (p < 0.001), gained 89.1 minutes in uninterrupted sleep episodes (p = 0.001), had 0.41 fewer nightly awakenings (p = 0.001), and had better sleep quality (p < 0.001) compared with baseline. Among all 72 completers at the end of the 39-week extension, 76% (55/72) achieved an overall improvement of ≥1 hour in total sleep time, sleep latency, or both. Caregiver sleep quality (PSQI, p < 0.001) and well-being (WHO-5, p = 0.001) significantly improved. Most frequent treatment-related adverse events were fatigue (5.3%) and mood swings (3.2%).
Why it matters
These findings show that prolonged-release melatonin maintains sleep benefits and tolerability for up to one year in pediatric patients with ASD and neurogenetic conditions, while also improving caregiver well-being.
Limits
The extension phase was entirely open-label with no placebo control group. All primary sleep measures relied on subjective caregiver-reported diaries and questionnaires rather than objective measurements such as actigraphy or polysomnography. There was notable attrition, with 72 of 95 enrolled patients completing the 39-week follow-up.
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- supports Clinical studies show melatonin at doses of 5 mg to 7 mg is effective for improving sleep in children with autism spectrum disorder.