SCN1A Variant and Cannabidiol Use

Dear Dr. Murphy

An anonymous survey was carried out amongst carers of patients with Dravet syndrome attending the neurology department in Temple Street Children’s University Hospital, Dublin. This survey was approved by the Ethics and Research committee (REC Number 17.004).

Dravet syndrome is a complex childhood epilepsy disorder usually associated with drug-resistant seizures and a high mortality rate, caused by variants in the sodium channel gene SCN1A1. Its incidence is reported as 1/15,700 – 1/40,000 births, accounting for only 1.4% of children with epilepsy2. Patients present in the first year of life with fever-associated generalized or focal seizures2. Other non-epileptic features include learning disability, ataxia, crouched gait and increased risk of sudden unexpected death in epilepsy (SUDEP)2. Many patients with Dravet syndrome have multi-drug resistant epilepsy and there has been growing interest in the use of cannabidiol in children with this disorder. Unfortunately there are few rigorous studies on cannabidiol use in paediatric epilepsy and in Dravet Syndrome, in particular. A recent study showed that cannabidiol reduces the frequency of convulsive seizures but was associated with adverse side effects including somnolence and impaired liver function tests1.Cannabidiol is not yet legalized in Ireland, but over-the-counter preparations containing cannabidiol or derivatives are available; usage was disclosed by some carers at clinic review.

The aim of this survey was to develop a better understanding of the use of cannabidiol among children with Dravet syndrome and the associated side effects of this drug.

One hundred percent of carers of children with Dravet syndrome (n=7) replied to the anonymous postal survey. All carers were open to the introduction of cannabidiol as a treatment for their child’s epilepsy. All responders were aware of the use of cannabidiol as a treatment of seizures, mostly through social media and media reports on children prescribed cannabidiol from centres in the United States. The majority of the cohort of carers was aware that cannabidiol is currently illegal in Ireland but available without prescription in forms such as Charlotte’s Web or CBD oil in hemp shops. All responders had considered using cannabidiol for treatment of their child’s epilepsy. However, nearly half of carers said they would be reluctant to start this treatment without recommendation and monitoring from their neurologist.

Interestingly, 14% of carers of children with Dravet syndrome had given cannabidiol to their child in an attempt to reduce seizure burden. We are unable to clarify the content of the preparations used.

The positive effects experienced included improved seizure control, better mood and behavior and increased alertness; no adverse side effects were reported. Notably, there was little awareness of the risks of combining clobazam with cannabidiol, which can result in respiratory depression3. The overall response from carers indicates that there is a real interest in the use of cannabidiol in the management of Dravet syndrome. Carers want clarity on the safety of cannabidiol for seizure control, and if appropriate, legalisation of this product for their children, under the support and guidance of their neurology consultant.

Yours sincerely,

C Reynolds, R Finnegan, E Forman, MD King.
Department of Neurology and Neurophysiology, Temple St Children’s University Hospital, Dublin 1

Rebecca Finnegan, Department of Neurology and Neurophysiology, Temple St Children’s University Hospital, Dublin 1
Email: [email protected]

1. Devinsky O, Cross H, Laux L, Marsh E, Miller E, Miller I, Nabbout R, Scheffer I, Thiele E, Wright S. Trial of cannabidiol for drug-resistant seizures in the Dravet syndrome. NEJM. 2017; 376:2011-2020
2. Gataullina S, Dulac O. From genotype to phenotype in Dravet disease. Seizure: Eur J Epilepsy. 2016
3. Vezyroglou K. Efficacy and safety of cannabidiol as add-on therapy in drug-resistant epilepsy, a single center experience. European Journal of Paediatric Neurology. 2017.