The Scottish Medicines Consortium (SMC) has rejected the application to recommend prolonged-release melatonin (Slenyto®) as a treatment for insomnia in children with autism spectrum disorder and/or Smith-Magenis syndrome (SMS). The decision was based on uncertainty that this medicine would offer value for money to NHS Scotland. The wider implication is that the SMC are saying that prolonged-release melatonin should not normally be prescribed on the NHS in Scotland for the treatment of insomnia in children with Smith-Magenis syndrome and that other treatment options should be explored instead. Prescriptions can be specially requested by the healthcare professional on an individual basis. The Smith-Magenis Syndrome (SMS) Foundation UK will continue to support families and medical practitioners with over 20 years of scientific and clinical evidence to justify the use of modified-release melatonin for those with this rare genetic disorder.
The child with Smith-Magenis syndrome has a different sleeping pattern to the rest of their family and community. Whilst they do not themselves have a sleep problem, their sleep profile creates challenges for others and their own safety. Their activity whilst others are sleeping can increase the risk of serious incidents for both the child (including through self-injury) and their family. Night time wake periods also disrupt the sleep of other members of the household. Reducing the negative impact of night waking on family sleep may also increase caregivers’ capacity to most effectively support children with the syndrome which is eroded through chronic sleep disturbance.
Sleep problems are highly characteristic of people with SMS, more so than of other people with an intellectual disability including autism (where sleep problems are also elevated). Sleep is a significant problem for 88% (#1) people with the syndrome, and that this is likely to have a biological cause in most people; SMS is characterised with an inverted circadian rhythm as shown in the graph (#2), promoting daytime sleeping and night-time waking. Sleep disturbance is evident both in people with SMS caused by a deletion and people with SMS caused by the mutation of RAI1.
Severe night waking is experienced by 80.8% of those with SMS, with 73.1% having severe early morning waking. Settling for sleep is not a significant problem (#3).
With inverted melatonin release as the primary cause of sleep disorder in SMS, then treatment providing evening modified-release melatonin and/or suppressing its daytime release (e.g. using beta-blockers) might be expected to be effective (#4). As well as improving night-time sleeping, normalising the circadian rhythm provides more opportunities for the family to engage in daytime activities improving overall quality of life. Parents and carers would be less tired with improved work prospects.
The Smith-Magenis Syndrome (SMS) Foundation UK is naturally disappointed at the decision from the Scottish Medicines Consortium. We will continue to raise awareness of the syndrome and encourage the adoption of interventions determined by the SMS researchers and clinical practitioners. We also recognise the extra stress this decision places on parents and carers in seeking medicines that have been suggested by the experts in Smith-Magenis syndrome, and we will continue to support families with the information and guidance needed for positive outcomes.
Slenyto® has been recommended by National Institute of Health and Care Excellence (NICE) for use in England. The All Wales Medicine Strategy Group is to review the application for Wales in November 2019.
(#1) Gender, genotype, and phenotype differences in Smith–Magenis syndrome: a meta-analysis of 105 cases.
Edelman, E. A., Girirajan, S., Finucane, B., Patel, P. I., Lupski, J. R., Smith, A. C. M., & Elsea, S. H. (2007).
Clinical genetics, 71(6), 540-550.
(#2) Inversion of the circadian rhythm of melatonin in the Smith-Magenis syndrome.
De Leersnyder, H., de Blois, M. C., Claustrat, B., Romana, S., Albrecht, U., von Kleist-Retzow, J. C., … & Munnich, A. (2001).
The Journal of paediatrics, 139(1), 111-116.
(#3) A cross-syndrome cohort comparison of sleep disturbance in children with Smith-Magenis syndrome (SMS), Angelman syndrome (AS), autism spectrum disorder (ASD) and tuberous sclerosis complex (TSC).
Trickett et al (2018).
Journal of Neurodevelopmental Disorders (2018) 10:9.
(#4) Inverted rhythm of melatonin secretion in Smith-Magenis syndrome: from symptoms to treatment.
De Leersnyder, H.
Trends Endocrinol Metab. 2006 Sep;17(7):291-8. Epub 2006 Aug 4.