49 - Efficacy

Efficacy

620 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 5 Melatonin in the treatment of insomnia in children and adolescents Insomnia is a common symptom in childhood. Underlying causes may be behavioural (inappropriate sleep associations or bedtime resistance), physiological (delayed sleep phase syndrome) or related to underlying mood disorders (anxiety, depression and bipolar disorder). All forms of insomnia are more common in children with learning difficulties, autism, ADHD and sensory impairments (particularly visual). Although behavioural interventions should be the primary intervention and have a robust ­evidence base, exogenous melatonin is now the first-­line medication prescribed for childhood insomnia (Figure 5.3).1 Melatonin is a hormone that is produced by the pineal gland in a circadian manner. The evening rise in melatonin, enabled by darkness, precedes the onset of natural sleep by about 2 hours.2 Melatonin is involved in the induction of sleep and in synchronisation of the circadian system. There is a wide variety of unlicensed fast-­release, slow-­release and liquid preparations of melatonin. Many products rely on food grade rather than pharmaceutical grade melatonin and some are expensive. In 2018 the European Medicines Agency and UK MHRA approved Slenyto, a paediatric-­appropriate prolonged-­release melatonin minitablet, for children with autism and insomnia. This approval was on the basis of a phase III multicentre randomised placebo-­controlled study of children with autism. Results of the study included clinically significant improvement in caregivers’ diary-­reported sleep latency, total sleep time and longest sleep period.3 Effects were maintained in the long ­term. The medication was well tolerated and no unexpected safety issues were reported. The study was the only ‘class 1’ rated study in the 2020 America Academy of Neurology practice guideline on the treatment for insomnia and disrupted sleep behaviour in ­children and adolescents with ASD.4 Secondary outcomes showed improvements in children’s social functioning and behaviour, and caregivers’ well-­being. A meta-­analysis of melatonin in ASD came to similar, positive conclusions.5 Two RCTs6,7 showed melatonin had comparable benefits when used to treat children with ADHD and insomnia. On this basis, the MHRA in the UK has approved various immediate-­release (tablet, e.g. Adaflex) and liquid (e.g. Colonis, Ceyesto) melatonin preparations for the management of sleep-­onset insomnia in children with ADHD. There is less evidence (and clinical consensus) for the use of melatonin in ­typically developing children, although a 2023 meta-­analysis provided a conditional recommendation ‘for use of melatonin in children and adolescents ­2–­20 years, who despite optimisation of sleep hygiene practices, continue to present with difficulties in daily functioning, due to chronic insomnia attributed to an underlying disorder’.8 Efficacy A meta-­analysis that included adult and paediatric studies of melatonin in primary sleep disorders demonstrated that melatonin modestly decreases sleep-­onset latency, increases total sleep time and improves overall sleep quality; effects that appear not to dissipate with continued melatonin use.9 A more recent (2022) analysis confirmed ­benefits only for sleep latency and sleep duration.10