Pediatric Prolonged-Release Melatonin for Sleep in Children with Autism Spectrum Disorder: Impact on Child Behavior and Caregiver’s Quality of Life

Abstract

A randomized, 13-weeks, placebo-controlled double-blind study in 125 subjects aged 2–17.5 years with Autism Spectrum Disorder or Smith-Magenis syndrome and insomnia demonstrated efficacy and safety of easily-swallowed prolonged-release melatonin mini-tablets (PedPRM; 2–5 mg) in improving sleep duration and onset. Treatment effects on child behavior and caregiver’s quality of life were evaluated. PedPRM treatment resulted in significant improvement in externalizing but not internalizing behavior (Strengths and Difficulties questionnaire; SDQ) compared to placebo (p = 0.021) with clinically-relevant improvements in 53.7% of PedPRM-treated versus 27.6% of placebo-treated subjects (p = 0.008). Caregivers’ quality of life also improved with PedPRM versus placebo (p = 0.010) and correlated with the change in total SDQ (p = 0.0005). PedPRM alleviates insomnia-related difficulties, particularly externalizing behavior in the children, subsequently improving caregivers’ quality of life.

Disturbances of Continuous Sleep and Circadian Rhythms Account for Behavioral Difficulties in Children with Autism Spectrum Disorder

“…This study thus corroborates the interest of the longest sleep episode as a marker of sleep quality related to daytime outcomes in children with ASD. In accordance with these results, a previous study found that a clinically meaningful improvement in the duration of the longest sleep episode, after a 13-week treatment of pediatric prolonged-release melatonin, led to a significant improvement in daytime behavioral problems in a population of 125 ASD children aged 2-17.5 years [46]. Additionally, this study found that the longest sleep episode was also associated with improvement in quality of life in parents.…”

Melatonin treatment of repetitive behavioral deficits in the Cntnap2 mouse model of autism spectrum disorder

“…Patients with repetitive behaviors, but not restrictive behaviors like the insistence on routine, experienced significant reported sleep problems even after controlling for anxiety ( Hundley et al, 2016 ). This suggests that melatonin may be better suited as an intervention for the subset of ASD patients with repetitive behaviors and sleep problems ( Schroder et al, 2019 ). Understandably, the work in patients is focused on treating the symptoms rather than understanding the underlying biology.…”

Perspective on Melatonin Use for Sleep Problems in Autism and Attention-Deficit Hyperactivity Disorder: A Systematic Review of Randomized Clinical Trials

“…Schroder et al found that ASD patients managed with prolonged release of melatonin showed improvement in externalizing behavior. This was measured by the strength and difficulty questionnaire (SDQ) with a treatment difference of -0.74 but was statistically not significant (P = 0.076) [25]. This study did find that melatonin at a higher dose above 10 mg is also not efficacious in improving sleep quality [25].…”

“…Five studies conducted in an outpatient setting evaluated the efficacy of melatonin on sleep patterns in ASD [21][22][23][24][25]. Double-blinded-RCT (DB-RCT) conducted by Maras et al included 95 pediatric patients with ASD and 51 patients received prolonged-release melatonin (2-10 mg/day) for 52 weeks and compared with placebo (N = 44).…”