Philadelphia – according to research presented at the annual meeting of the American Academy of Neurology. The two dosages in the study appear to have comparable efficacy.
“It’s exciting to be able to offer another alternative for children with this debilitating form of epilepsy and their families,” said, director of the epilepsy and neurophysiology program at Nicklaus Children’s Hospital in Miami, in a . “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 CBD is a major victory.”
Dravet syndrome is a rare developmental and epileptic encephalopathy. Onset occurs during infancy, and the syndrome is associated with drug-resistant seizures. Dr. Miller and colleagues designed a trial to evaluate the efficacy of two dosages of CBD as adjunctive anticonvulsant therapy in patients with Dravet syndrome and drug-resistant seizures.
The study population included 199 patients whose seizures were recorded for 4 weeks at baseline. The investigators randomized participants in approximately equal groups to receive placebo or highly purified CBD (the formulation approved under the name Epidiolex) at 20 mg/kg per day or 10 mg/kg per day. The study’s primary outcome was the change from baseline in frequency of convulsive seizures over 14 weeks of treatment.
Participants’ mean age was 9 years. Patients were taking a median of three concomitant antiepileptic drugs and had discontinued a median of four such drugs previously.
The reduction in the frequency of convulsive seizures was 46% for the high dose of CBD, 49% for the low dose of CBD, and 27% for placebo. The proportion of participants with a 50% or greater reduction in seizures was 49% in the high-dose group, 44% in the low-dose group, and 26% among controls. In addition, the reduction in the rate of total seizures was 47% for the high-dose group, 56% for the low-dose group, and 30% among controls.
The rate of adverse events was similar in all groups (90% for the high-dose group, 88% for the low-dose group, and 89% for controls). The five most common adverse events were diarrhea, somnolence, pyrexia, fatigue, and decreased appetite. The rate of serious adverse events was 25% for the high-dose group, 20% for the low-dose group, and 15% for controls. Discontinuations because of adverse events were limited to the high-dose group (7%). The rate of transaminases that exceeded three times the upper limit of normal was 19% in the high-dose group and 5% in the low-dose group. All of these elevations resolved. No patients died.
“Based on these results, dose increases above 10 mg/kg per day should be carefully considered based on the effectiveness and safety for each individual,” said Dr. Miller.
GW Research, the developer of cannabidiol, supported the study. GW operates through its affiliate Greenwich Biosciences in the United States. Dr. Miller has received compensation and research support from several companies, including GW Pharma.
SOURCE: Miller I et al. AAN 2019, .