Cannabidiol may halve seizure risk in Dravet syndrome
A 10 or 20 mg/kg daily dose of cannabidiol could almost halve the risk of seizures in children with Dravet syndrome, according to the phase III GWPCARE2* study presented at the American Academy of Neurology annual meeting (AAN 2019).
“[Cannabidiol at doses of 10 or 20 mg/kg/day] significantly reduced seizure frequency versus placebo,” said study author Dr Ian Miller from the Nicklaus Children’s Hospital in Miami, Florida, US.
Participants in this multicentre, double-blind study were 199 children (mean age, 9 years) with Dravet syndrome who were receiving a median three antiepileptic drugs (reduced from a median of four drugs). They were randomized to receive highly-purified cannabidiol at doses of either 20 mg/kg/day (n=67) or 10 mg/kg/day (n=67), or placebo (n=65) for 14 weeks. To identify seizure frequency at baseline, the researchers recorded seizure incidence for 4 weeks prior to patients initiating treatment.
At week 14, children who received cannabidiol had a greater reduced risk of convulsive seizures compared with placebo recipients, regardless of cannabidiol dose (reduction of 46 percent and 49 percent for 20 and 10 mg/kg/day doses, respectively, vs 27 percent for placebo; p=0.0299 and p=0.0095 vs placebo, respectively). [AAN 2019, abstract 006]
Children on cannabidiol also experienced greater reductions in total seizures compared with placebo recipients (reductions of 47 percent and 56 percent for 20 and 10 mg/kg/day, respectively, vs 30 percent for placebo; p=0.0255 and p=0.0003, respectively).
More cannabidiol than placebo recipients experienced ≥50 percent reductions in seizure incidence (49 percent and 44 percent for 20 and 10 mg/kg/day, respectively, vs 26 percent for placebo; p=0.0069 and p=0.0332, respectively).
The adverse event (AE) rate was comparable among treatment arms at 90, 88, and 89 percent in the cannabidiol 20 mg/kg/day, 10 mg/kg/day, and placebo groups, respectively, while serious AEs occurred in 25, 20, and 15 percent of those respective groups. The most frequently reported AEs were reduced appetite, diarrhoea, somnolence, pyrexia, and fatigue. AE-related discontinuations occurred solely among patients who received cannabidiol 20 mg/kg/day (7 percent) and there were no deaths.
More patients taking the 20 mg/kg/day compared with the 10 mg/kg/day dose of cannabidiol experienced elevations in transaminase levels ≥3 times the upper limit of normal (19 percent vs 5 percent). None of the patients experienced elevated bilirubin levels.
“Based on these results, dose increases above 10 mg/kg/day should be carefully considered based on the effectiveness and safety for each individual,” said Miller.
“The children in this study had already tried an average of four epilepsy drugs with no success and at the time were taking an average of three additional drugs, so to have this measure of success with cannabidiol is a major victory,” he added. “It’s exciting to be able to offer another alternative for children with this debilitating form of epilepsy and their families,” he said.
In June 2018, the US Food and Drug Administration (FDA) approved cannabidiol for the treatment of seizures occurring due to Dravet syndrome in individuals aged ≥2 years, the first FDA drug approval for patients with this condition. [https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-comprised-active-ingredient-derived-marijuana-treat-rare-severe-forms]