Melatonin Treatment for Pediatric Patients with Insomnia: Is There a Place for It?

Abstract

Sleep is a vital physiological function that is impaired in ranges from 10% in the typically developing pediatric population to over 80% in populations of children with neurodevelopmental disorders and/or psychiatric comorbidities. Pediatric insomnia disorder is an increasing public health concern given its negative impact on synaptic plasticity involved in learning and memory consolidation but also on mood regulation, hormonal development and growth, and its significant impact on quality of life of the child, the adolescent and the family. While first-line treatment of pediatric insomnia should include parental education on sleep as well as sleep hygiene measures and behavioural treatment approaches, pharmacological interventions may be necessary if these strategies fail. Melatonin treatment has been increasingly used off-label in pediatric insomnia, given its benign safety profile. This article aims to identify the possible role of melatonin treatment for pediatric insomnia, considering its physiological role in sleep regulation and the differential effects of immediate release (IR) versus prolonged release (PR) melatonin. For the physician dealing with pediatric insomnia, it is particularly important to be able to distinguish treatment rationales implying different dosages and times of treatment intake. Finally, we discuss the benefit–risk ratio for melatonin treatment in different pediatric populations, ranging from the general pediatric population to children with different types of neurodevelopmental disorders, such as autism spectrum disorder or ADHD.

Management of sleep disorders in autism spectrum disorder with co-occurring attention-deficit hyperactivity disorder: update for clinicians

“…Further influence results from disturbed signalling of intracellular melatonin receptor type 1A, inflammation of the central and peripheral immune systems, and immune signalling dysregulation. 54,55 Melatonin pathway dysregulation is likely to be the mechanism driving melatonin variations. 56…”

“…A paucity of high-quality evidence demonstrating the effectiveness of non-pharmacological interventions for ASD/ADHD/sleep disruption populations is concerning, with small percentages of ASD children with behavioural insomnia reported to respond to combined behaviour therapy and sleep hygiene. 37,54 However, significant efficacy has been demonstrated for Sleeping Sound with ADHD (SSADHD), a brief behavioural sleep intervention for individuals with ASD/ADHD. 78…”

“…Further influence results from disturbed signalling of intracellular melatonin receptor type 1A, inflammation of the central and peripheral immune systems, and immune signalling dysregulation. 54,55 Melatonin pathway dysregulation is likely to be the mechanism driving melatonin variations. 56 Based on modelling from diffusion magnetic resonance imaging, similar white matter tract deviations have been reported to be shared by ASD and ADHD patients, with inter-individual variability relative to the norm in a degree of deviation.…”

“…Approaches to distinguish between sleep disruptions in clinical practice, and treatment rationales guiding differing dosages and times of administration, follow. 37,54 This allows for accurate case formulation of predisposing, precipitating, perpetuating, and positive or preventive factors, and appropriate psychosocial treatment with or without pharmacological interventions, 67 including collaboration with sleep specialists when needed. 23 A meta-synthesis of multiple therapeutic interventions concluded that compared with other interventions for ameliorating multiple ASD/sleep disruption domains of sleep problems, melatonin, behavioural interventions and education/parent education appear to be the most effective.…”

“…No adverse effects or differences between the groups were noted. 54 A large multicentre collaborative phase III study with adequate sleep hygiene interventions demonstrated highly significant improvement in SOL (as documented using an electronic sleep diary), irritability, inappropriate speech, hyperactivity and stereotypical behaviour. No treatment-emergent adverse effects occurred.…”