Cannabidiol is equally effective at reducing seizures in children and adolescents with treatment-resistant Dravet syndrome at low and high doses.
An international study of 199 eligible paediatric patients, from 38 centres across the US, Spain, Poland, the Netherlands, Australia and Israel, compared seizure frequency during 14 weeks of cannabidiol treatment at two doses, of 10 mg/kg/d or 20 mg/kg/d, and placebo.
All patients maintained doses of their regular medications including valproate, clobazam and stiripentol.
The study, published in JAMA Neurology, found the percentage reduction in convulsive seizure frequency from baseline was 48.7% for the CBD10 group, 45.7% for the CBD20 group, and 26.9% for the placebo group.
“Similarly, the percentage reduction from baseline in convulsive seizure frequency during the 12-week maintenance period was 49.2% for the CBD10 group, 48.6% for the CBD20 group, and 28.6% for the placebo group,” the authors wrote.
The proportion of patients achieving at least a 50% reduction from baseline in convulsive seizure frequency during the treatment period was 43.9% for the CBD10 group and 49.3% for the CBD20 group, compared to 26.2% for the placebo group.
The proportion of patients achieving at least a 75% reduction from baseline in convulsive seizure frequency was 30.3%, 17.9%, and 6.2% for the respective groups.
Caregivers of cannabidiol-treated patients were significantly more likely to report an improvement in overall condition than those of the control group.
And patients in the treatment groups were more likely to report feeling improved than those receiving placebo.
However serious adverse events were more common with the higher cannabidiol dose.
“As in prior studies, the 20-mg/kg/d cannabidiol dose and valproate were independent risk factors for elevated liver transaminase levels. Notably, only 6.8% of patients receiving valproate in the CBD10 group had transaminase elevations greater than 3 times the upper limit of the reference range compared with 27.7% of patients receiving valproate in the CBD20 group.”
The study authors, including Australian neurologist Professor Ingrid Scheffer, said the potential for drug-drug interactions between cannabidiol and other medications warranted careful monitoring of adverse events by a clinician.
The most common adverse events in any group were decreased appetite, diarrhoea, somnolence, pyrexia, and fatigue.
“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,” the study concluded.
“There was no appreciable difference in the efficacy between the 2 active treatment doses, but because individual responses vary, dose escalation to 20 mg/kg/d in patients requiring better seizure control may still be warranted if safety and tolerability allow.”