Trial of cannabidiol for drug-resistant seizures in the dravet syndrome

Orrin Devinsky*, J. Helen Cross, Linda Laux, Eric Marsh, Ian Miller, Rima Nabbout, Ingrid E. Scheffer, Elizabeth A. Thiele, Stephen Wright

*Corresponding author for this work

Research output: Contribution to journalArticle

463 Scopus citations

Abstract

BACKGROUND The Dravet syndrome is a complex childhood epilepsy disorder that is associated with drug-resistant seizures and a high mortality rate. We studied cannabidiol for the treatment of drug-resistant seizures in the Dravet syndrome. METHODS In this double-blind, placebo-controlled trial, we randomly assigned 120 children and young adults with the Dravet syndrome and drug-resistant seizures to receive either cannabidiol oral solution at a dose of 20 mg per kilogram of body weight per day or placebo, in addition to standard antiepileptic treatment. The primary end point was the change in convulsive-seizure frequency over a 14-week treatment period, as compared with a 4-week baseline period. RESULTS The median frequency of convulsive seizures per month decreased from 12.4 to 5.9 with cannabidiol, as compared with a decrease from 14.9 to 14.1 with placebo (adjusted median difference between the cannabidiol group and the placebo group in change in seizure frequency, -22.8 percentage points; 95% confidence interval [CI], -41.1 to -5.4; P = 0.01). The percentage of patients who had at least a 50% reduction in convulsiveseizure frequency was 43% with cannabidiol and 27% with placebo (odds ratio, 2.00; 95% CI, 0.93 to 4.30; P = 0.08). The patient's overall condition improved by at least one category on the seven-category Caregiver Global Impression of Change scale in 62% of the cannabidiol group as compared with 34% of the placebo group (P = 0.02). The frequency of total seizures of all types was significantly reduced with cannabidiol (P = 0.03), but there was no significant reduction in nonconvulsive seizures. The percentage of patients who became seizure-free was 5% with cannabidiol and 0% with placebo (P = 0.08). Adverse events that occurred more frequently in the cannabidiol group than in the placebo group included diarrhea, vomiting, fatigue, pyrexia, somnolence, and abnormal results on liver-function tests. There were more withdrawals from the trial in the cannabidiol group. CONCLUSIONS Among patients with the Dravet syndrome, cannabidiol resulted in a greater reduction in convulsive-seizure frequency than placebo and was associated with higher rates of adverse events. (Funded by GW Pharmaceuticals; ClinicalTrials.gov number, NCT02091375.).

Original languageEnglish (US)
Pages (from-to)2011-2020
Number of pages10
JournalNew England Journal of Medicine
Volume376
Issue number21
DOIs
StatePublished - May 25 2017

ASJC Scopus subject areas

  • Medicine(all)

Fingerprint Dive into the research topics of 'Trial of cannabidiol for drug-resistant seizures in the dravet syndrome'. Together they form a unique fingerprint.

  • Cite this

    Devinsky, O., Cross, J. H., Laux, L., Marsh, E., Miller, I., Nabbout, R., Scheffer, I. E., Thiele, E. A., & Wright, S. (2017). Trial of cannabidiol for drug-resistant seizures in the dravet syndrome. New England Journal of Medicine, 376(21), 2011-2020. https://doi.org/10.1056/NEJMoa1611618