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UK/FLY/2023/2543

June 2023

ASD

Insomnia in Children with ASD:
Unlicensed/Off-label Pharmacotherapy

Current practices recommend parent-directed behavioural sleep interventions as first-line management for paediatric insomnia in ASD/NGD (Neurogenetic Disorders), with reportedly a 25% response rate.

Pharmacotherapy is often considered when the behavioural intervention fails.3 Until now, however, there were no medications with regulatory approval for the treatment of chronic insomnia in children and adolescents and this was particularly problematic for children with ASD. Consequently, physicians often prescribe drugs off-label. For example, Circadin® (2mg prolonged-release melatonin which is licensed for short-term treatment of primary insomnia in patients ≥55 years) is commonly used, albeit that to facilitate swallowing, the tablet is often sub-divided or crushed. In so doing, however, the intended release characteristics are destroyed, and the dose is effectively rendered immediate release.12

In a study of children who failed to improve on behavioural intervention alone, immediate release (IR) melatonin demonstrated beneficial effects on sleep latency (time to fall asleep) and, to a lesser extent, on total sleep time.

The authors concluded, however, that children gained little additional sleep when taking immediate release melatonin since although they fell asleep significantly faster, waking times were earlier (phase shifting). Child behaviour and family functioning outcomes did not significantly improve.16

Licensed and unlicensed liquid formulations of melatonin are also available; however, these are all immediate release, typically contain additives and preservatives, and require a willing patient for their effective administration. Moreover, unregulated melatonin preparations, or food supplements, are used despite concerns over their provenance, quality, potential safety hazards and lack of evidence for long-term efficacy and safety. Other medications are used outside of licence including antihistamines, alpha-adrenergic agonists (clonidine), antidepressants, and antipsychotics, for their sedative side effects, but in absence of proven safety or efficacy.6

References:

3. Gringras, P. et al. Efficacy and Safety of Pediatric Prolonged-Release Melatonin for Insomnia in Children with Autism Spectrum Disorder. J Am Acad Child Adolesc Psychiatry. 2017;56(11):948-957

6. Maras, A. et al. Long-Term Efficacy and Safety of Pediatric Prolonged-Release Melatonin for Insomnia in Children with Autism Spectrum Disorder. Jnl Child and Adolesc Psychpharmacol. 2018; doi 10.1089:1-12

12. Chua, HM. et al. Dissolution of Intact, Divided and Crushed Circadin Tablets: Prolonged vs. Immediate Release of Melatonin. Jnl Pharmaceutics. 2016;8(2):1-11

16. Gringras P, et al. Melatonin for sleep problems in children with neurodevelopmental disorders: randomised double masked placebo-controlled trial. BMJ. 2012;345:e6664