Epilepsy is a relatively common condition that is characterised by repeated unprovoked seizures. The condition affects the brain, causing bursts of electrical activity – known as seizures. While anyone may experience a single seizure, an epilepsy diagnosis may be made if clinicians believe that the patient is at an increased risk of experiencing further seizures. Epilepsy usually starts in children or people over the age of 60; however, it can develop at any age. It is estimated that around 65 million people are affected by epilepsy, globally.
Current Treatment Options for Epilepsy
Epilepsy can cause serious disruption and is often associated with reduced quality of life and significant social impacts, including educational attendance, stigmatisation, discrimination, and social isolation. A number of anti-seizure medications are now available; however, around a third of patients are still unable to achieve seizure control. Some patients’ epilepsy is non-responsive to conventional treatment (known as treatment-resistant epilepsy) and few patients are currently suitable for surgery – the most successful treatment option in these cases.
There is a clear need for the development of novel treatment options to reduce seizure frequency and severity in patients who may otherwise struggle to successfully control their seizures.
Medical Cannabis and Epilepsy
In November 2018, the UK officially rescheduled cannabis, allowing for its medicinal use in a number of conditions. One of the most prominent topics during the campaign that led to this landmark event was the potential of medical cannabis as a treatment for epilepsy. Treatment-Resistant Epilepsy is now one of only a handful of conditions for which the National Institute of Health and Care Excellence (NICE) recommends a trial of Epidyolex (a cannabidiol isolate oil) when other options have proven ineffective for children with Lennox-Gastaut and Dravet Syndromes.
In addition to Epidyolex there have been much speculation about the use of unlicensed medical cannabis products. However, there i a paucity of high-quality evidence of the safety and efficacy of these products. To help address this issue, Sapphire Medical Clinics established the UK Medical Cannabis Registry to record the outcome measures of patients receiving CBMPs for the treatment of various conditions, including treatment-resistant epilepsy.
Data Collection for the UK Medical Cannabis Registry
The UK Medical Cannabis Registry, which has been managed by Sapphire Medical Clinics since 2019, is the first UK patient registry to collect data regarding CBMP prescription formulations, patient demographics, patient-reported outcome measures (PROMs) and adverse events (AEs). The current analysis assessed data from paediatric (aged under 18) patients with TRE who have received a medical cannabis prescription.
Measuring Patient Outcomes
For each patient, seizure frequency was monitored and recorded on a number-per-month basis at 1 month, 3 months, and 6 months. Statistical significance in seizure frequency was determined by a p-value<0.050.
Adverse Events (AEs)
Adverse events were recorded following the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE). This method allows for comprehensive reporting and grading comparable to other studies. The severity of AEs is graded using unique clinical descriptions specific to each AE. Patients were prompted to report AEs during the completion of their PROMs; clinicians can also update any AEs reported during clinical consultations.
Results of the Analysis
A total of 35 paediatric patients were included in the final analysis. Twelve (34.3%) of the participating patients had a diagnosed epilepsy syndrome (Lennox-Gastaut syndrome [n=5]; Dravet syndrome [n=2]; all other syndromes n=1 and redacted to maintain anonymity), whilst 9 (25.7%) had a genetic cause for their epilepsy. The remaining aetiologies (n=14) were either idiopathic or not known. Patients had used a median of seven (3-15) anti-seizure medications between the initiation of medical cannabis treatment. They were currently using a medial of 2 (1-4) anti-seizure medications concurrently alongside CBMPs.
CBMPs prescribed
Participating patients received CBMPs, including oil-based isolated cannabinoids or broad-spectrum products including cannabinoids, terpenes, and flavonoids. Nineteen patients had received CBD isolate therapy, while 17 patients received broad-spectrum CBD or CBD and Δ9-THC combination therapies, respectively. At the time of data extraction, four patients were being treated actively with CBD isolate, while 14 and 17 patients were being treated with broad-spectrum or CBD and Δ9-THC combination therapies, respectively.
Changes in Seizure Frequency
A total of 23 patients experienced a change in seizure frequency.
Adverse Events (AEs)
A total of 26 adverse events were reported by 16 patients (45.7%) and the majority were mild (n=12; 34.2%) or moderate (n=10; 28.6%). Interestingly, there was no significant difference in the proportion of patients who experienced adverse events between those currently using CBD isolates, broad-spectrum CBD, and both CBD and Δ9-THC products
Conclusions
This case series analysed a small sample of paediatric patients who were prescribed CBMPs for treatment-resistant epilepsy after traditional anti-seizure medications had proven ineffective. The changes to seizure frequency observed in this study are similar to that reported in the existing literature. Despite the small sample size, the findings of this analysis provide valuable insights into medical cannabis and epilepsy to guide further research.
