Devinsky O, Cross H, Laux L, et al.
New England Journal of Medicine 2017;376(21):2011-2020.
The Dravet syndrome is a rare genetic form of epilepsy. These patients often have many daily seizures and can be difficult to control with drug therapy. Prior to this study, 4 small trials using cannabidiol as an adjunct seizure treatment have been completed with mixed results. Prior preclinical research indicated cannabidiol exhibited some anti-seizure activity. Cannabidiol lacks activity at the cannabinoid receptors, thereby avoiding some of the psychoactivity common with THC.
This randomized, double-blind, placebo-controlled trial included 120 patients aged 2-18 years with an established diagnosis of Dravet syndrome, stable therapy, and uncontrolled seizures. Cannabidiol was dosed 5, 10, or 20 milligrams per kilogram of body weight per day divided twice daily.
The primary end point was seizure frequency percentage change over the 14-week treatment period. Secondary end points were measured using a variety of surveys to assess improvement, duration of seizures, sleep disruption, and behavior. In addition, safety was monitored by adverse event reporting and objective laboratory and physical exam findings.
A total of 12 patients, 9 in the cannabidiol group and 3 in the placebo group, withdrew prior to completion of the trial. In the cannabidiol group, seizure frequency decreased from a median of 12.4 to 5.9 seizures per month. In the placebo group, seizure frequency decreased from a median of 14.9 to 14.1 seizures per month. The difference in favor of cannabidiol was seen within the first month of treatment.
Common adverse events in the cannabidiol group were vomiting, fatigue, pyrexia, upper respiratory tract infections, decreased appetite, convulsion, lethargy, somnolence, and diarrhea. Adverse events were commonly reported within the first 2 weeks of therapy during dose titration. Other noted adverse effects in conjunction with other medications included somnolence, being more common while taking clobazam (a benzodiazepine). Elevated liver aminotransferase enzymes were more commonly seen with patients also taking valproate derivatives. However, 9 of the 12 patients continued the medications and the levels returned to normal.
Overall, this study does show improvement in seizure activity when cannabidiol is added to other therapies in children with Dravet syndrome. Side effects can be intolerable as evidenced by the incidence of side effects and frequency of patients withdrawing from the trial. Since Dravet syndrome can be very difficult to treat and contributes to high mortality rate in these children, the addition of cannabidiol may prove to helpful in certain cases. The risks and benefits need to be weighed carefully. In addition, the findings of this study cannot be transferred to include treatment of other seizure disorders at this time.