Cannabidiol Reduces Seizure Frequency in Refractory Dravet Syndrome
Results of the phase 3, placebo-controlled trial support previous findings from an expanded-access program.
HOUSTON – Adjunctive treatment with cannabidiol reduces convulsive seizure frequency in patients with Dravet syndrome, according to results from a phase 3 study presented at the 2016 American Epilepsy Society Annual Meeting.
While efficacy has previously been demonstrated in this population in data reported from an expanded-access program, this is the first placebo-controlled trial examining the efficacy and safety of cannabidiol in refractory Dravet syndrome.
A team of researchers led by Professor Helen Cross, MD, PhD, of the Institute for Child Health at University College London, United Kingdom, conducted a randomized, double-blind, placebo-controlled, multicenter trial involving 120 patients from the United States and Europe. Mean age was 10 years, and 29% of the participants were 6 years and younger. Sixty-one patients were randomly assigned to receive cannabidiol, and 59 patients received placebo. Prior to the trial, patients had received a median of 4 antiepileptic drugs (AEDs) and were currently taking a median of 3 AEDs. Patients were treated over 14 weeks, including a 2-week dose-escalation period during which patients were titrated up to 20 mg/kg/d of cannabidiol delivered in 2 doses.
Over the course of the study, patients who received cannabidiol experienced a 39% median reduction in seizure frequency vs a 13% reduction in the placebo group (P= .0123). This result was evident throughout the 14-week treatment period and 12-week maintenance period. Three patients experienced complete freedom from seizures during the treatment period.
Adverse events occurred in 93.4% of patients who received cannabidiol (74.6% in placebo); however, 84% were deemed to be mild or moderate in nature. The most common adverse events included somnolence, diarrhea, reduction in appetite, fatigue, fever, vomiting, lethargy, upper respiratory tract infection, and convulsion. Serious adverse events occurred in 16.4% of patients who received cannabidiol compared with 5.1% of patients who received placebo. Approximately 8% of patients receiving cannabidiol were considered to have experienced serious treatment-related adverse events; however, the investigators attributed most of the events to drug-drug interactions. No deaths were reported.
The results of this study are in line with previous data from an expanded-access program and provide class 1 evidence for the efficacy and tolerability of cannabidiol as an adjunctive treatment in individuals with refractory Dravet syndrome.
Disclosure: This study was supported by GW Pharmaceuticals, the manufacturer of Epidiolex, a 98% pure formulation of cannabidiol.
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Cross JH, Devinsky O, Laux L, et al. Cannabidiol (CBD) reduces convulsive seizure frequency in Dravet syndrome: Results of a multi-centered, randomized, controlled study (GWPCARE1). Presented at: 2016 American Epilepsy Society Annual Meeting; December 2-6, 2016; Houston, TX. Abstract 2.362.