Neurology Today Conference Reporter: AAN Annual Meeting

Access daily, concise peer-reviewed reports from the AAN Annual Meeting selected by the Neurology Today editors.

Thursday, April 27, 2017

Cannabidiol Found to Reduce Seizure Frequency in Dravet Syndrome


BOSTON–A randomized, double-blind, placebo-controlled study found that pharmaceutically-produced cannabidiol (CBD) was effective for reducing seizure frequency and was generally well tolerated in children with Dravet syndrome, researchers reported here Tuesday at the AAN Annual Meeting.

The findings support making available an additional medication for very complex patients, J. Helen Cross, MD, the Prince of Wales's Chair of Childhood Epilepsy and head of the developmental neurosciences program at University College London Institute of Child Health, told the Neurology Today Conference Reporter. "Currently, we have very little in our armamentarium for this specific form of epilepsy. Our trial demonstrated that this form of pure, pharmaceutical cannabidiol shows above-and-beyond effectiveness."

For the study, researchers enrolled 120 children and adolescents — the average age was 10 — with Dravet syndrome, a rare genetic developmental epileptic encephalopathy associated with drug-resistant seizures. Participants had previously tried an average of four antiepileptic drugs (AEDs) and were currently taking at least three. Participants were randomized to receive an oral solution of CBD up to 20 mg/kg per day (n=61) or to receive placebo (n=59). The primary endpoints were a change in convulsive seizure frequency over the 14-week dose escalation and treatment period compared with a four-week baseline period, and at least a 50 percent reduction in seizure frequency.

Among the findings, seizure frequency decreased from an average of 12.4 to 5.9 seizures per month (a median reduction of 39 percent) in patients receiving CBD compared to 14.9 to 14.1 (a median reduction of 13 percent) in patients receiving placebo; this corresponded with a 23 percent between-group difference (CI: -41.4 to -5.4, p=0.012). Participants who received CBD were nearly twice as likely to have at least a 50 percent reduction in convulsive seizure frequency compared to patients who received placebo (42.6 percent vs 27.1 percent, respectively; OR=2.0, CI: 0.93 to 4.3, p=0.078). There was no between-group difference in non-convulsive seizures.

Serious adverse events, however, were reported more often in patients receiving CBD than patients receiving placebo (16.4 percent versus 5.1 percent, respectively). These included somnolence, fatigue, and elevated liver enzymes. In the CBD cohort, 8.2 percent of the adverse events were considered treatment-related, and these children discontinued treatment. However, the study authors concluded, CBD was "generally well tolerated."

Dr. Cross noted, however, that the relatively brief outcome period — 14 weeks — may limit the results. She added that planned future trials will examine longer outcome periods as well as the efficacy of CBD for other rare epilepsy syndromes, such as Lennox-Gastaut syndrome.​

Commenting on the study, Joseph I. Sirven, MD, FAAN, professor and chair of neurology at the Mayo Clinic in Scottsdale, AZ, said the study findings are important. "This study provides Class A, Level 1 evidence supporting the use of CBD for convulsive seizures in Dravet syndrome, which is a very difficult syndrome to manage. The results provide evidence of significant efficacy for convulsive seizures and add to the growing body of evidence that supports cannabidiol use for epilepsy."