Cannabidiol daily doses of 10 or 20 mg/kg can be a safe and effective adjunct treatment to reduce seizure in patients with highly resistant Dravet syndrome, according to study results published in JAMA Neurology.
Previous studies have supported the safety and efficacy of cannabidiol at a daily dose of 20 mg/kg as an add-on antiepileptic treatment in patients with Dravet syndrome. The goal of the current study was to assess the efficacy and safety of 2 daily doses of cannabidiol, 10 mg/kg or 20 mg/kg, in children with Dravet syndrome.
The double-blind, placebo-controlled, randomized clinical trial included children aged 2 to 18 years from 38 centers in the United States, Spain, Poland, the Netherlands, Australia, and Israel with a confirmed diagnosis of Dravet syndrome and at least 4 convulsive seizures during a 4-week baseline period while receiving antiepileptic therapy.
The patients were randomly assigned to receive cannabidiol oral solution at a daily dose of 10 (CBD10) or 20 (CBD20) mg/kg, or matched placebo in 2 equally divided doses for 14 weeks. The primary outcome was the change in the frequency of convulsive seizure frequency from baseline.
A total of 198 patients (mean age, 9.3 years; 52.5% girls) were enrolled in the study; of these, 65 received placebo, 66 received CBD10, and 67 received CBD20. A total of 190 patients completed the treatment period, and 186 (97.9%) entered the open-label extension trial.
Convulsive seizure frequency compared with baseline was reduced by 48.7% in the CBD10 group and by 45.7% in the CBD20 group compared with 26.9% in the placebo group. The percentage reduction from placebo was 29.8% (95% CI, 8.4%-46.2%; P =.01) for the CBD10 group and 25.7% (95%CI, 2.9%-43.2%; P =.03) for the CBD20 group.
The most common adverse events occurring in ≥10% of patients in any group included decreased appetite, diarrhea, somnolence, pyrexia, and fatigue. Serious adverse events occurred in 40 patients (10 in the placebo group, 13 in the CBD10 group, and 17 in the CBD20 group). Elevated liver transaminase levels occurred more frequently in the CBD20 (n=13) than the CBD10 (n=3) group, with all affected patients receiving concomitant valproate sodium.
The study had several limitations, according to the researchers, including the short-term follow-up period, limited option to assess the effects of specific drug combinations as cannabidiol was added to various antiepileptic regimens, and lack of data on the safety and efficacy of cannabidiol in daily doses <10 mg/kg.
“Our key finding is the significant and clinically meaningful reduction of seizures with an acceptable safety profile for both cannabidiol doses in patients with highly treatment-resistant Dravet syndrome,” concluded the researchers.
Disclosure: This clinical trial was supported by GW Research, Ltd. Please see the original reference for a full list of authors’ disclosures
Miller I, Scheffer IE, Gunning B, et al. Dose-ranging effect of adjunctive oral cannabidiol vs placebo on convulsive seizure frequency in Dravet syndrome: a randomized clinical trial [published online March 2, 2020]. JAMA Neurol. doi:10.1001/jamaneurol.2020.0073