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BOSTON – Adjunctive treatment with cannabidiol reduced the frequency of drop seizures in patients with treatment-refractory Lennox-Gastaut syndrome, according to results from 2 phase 3 studies reported at the 2017 American Academy of Neurology (AAN) Annual Meeting, April 22-28 in Boston.
The studies, GWPCARE3 and GWPCARE4, both multicenter, randomized, double-blind, placebo-controlled trials, evaluated the safety and efficacy of cannabidiol in patients with Lennox-Gastaut syndrome who were taking other antiepileptic drugs (AEDs).
In the GWPCARE3 study,1 Anup Patel, MD, of Nationwide Children’s Hospital in Columbus, Ohio, and colleagues conducted a dose-ranging trial in 225 patients aged 2 to 55 years with a confirmed diagnosis of Lennox-Gastaut syndrome with at least 8 drop seizures over a 4-week period at baseline and confirmed failure of at least 1 AED.
Patients (median age=16 years; median monthly drop seizure frequency=85) were randomly assigned to receive either cannabidiol 20 mg/kg (n=76), 10 mg/kg (n=73), or placebo (n=76). Patients were taking a median of 3 concomitant AEDs during the trial. Ultimately 13 patients (9 cannabidiol 20 mg/kg, 2 cannabidiol 10 mg/kg, 2 placebo) withdrew early from the study.
Patients who received cannabidiol 20 mg/kg or 10 mg/kg had a significantly greater reduction in frequency of drop seizures compared with placebo (42% and 37% vs 17%; P =.0047 and P =.0016). Adverse events occurred in 94% of patients who received cannabidiol 20 mg/kg, 84% in the 10-mg/kg group, and 72% in the placebo group; the most common adverse events were somnolence and decreased appetite. Serious adverse events were reported in 5 and 2 patients in the 20-mg/kg and 10-mg/kg cannabidiol groups, respectively. Notably, some instances of elevated liver enzymes were documented.
The GWPCARE4 trial,2 led by Jacqueline French, MD, of New York University School of Medicine, included 171 patients aged 2 to 55 years with a confirmed diagnosis of Lennox-Gastaut syndrome with at least 2 drop seizures per week and confirmed failure of at least 1 AED. Patients were randomly assigned to receive either 20 mg/kg/d of cannabidiol (n=86) or placebo (n=85) for 14 weeks, 2 of which were for titration. Ultimately, 14 patients assigned to a treatment arm and 1 patients assigned to placebo withdrew early.
During the trial, patients were taking a median of 3 concomitant AEDs. Compared with placebo, those who received cannabidiol experienced a 44% median reduction in monthly drop seizure frequency (44% vs 22%; P =.0135), which was established during the first 4 weeks of the maintenance period.
Adverse events occurred in 86% of patients who received cannabidiol compared with 69% of those who received placebo; the most common were diarrhea, somnolence, pyrexia, decreased appetite, and vomiting. Serious adverse events were reported in 9 patients who received cannabidiol and 1 patient who received placebo. One death occurred in the treatment group, though this was not attributed to treatment.
Overall, both trials demonstrate that cannabidiol may be a safe and effective treatment for patients with Lennox-Gastaut syndrome who experience frequent drop seizures.
Disclosure: Both clinical trials were supported by GW Research, Ltd.
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- Patel A, Devinsky O, Cross JH, et al. Cannabidiol (CBD) significantly reduces drop seizure frequency in Lennox-Gastaut syndrome (LGS): results of a dose-ranging, multi-center, randomized, double-blind, placebo-controlled trial (GWPCARE3). Presented at: 2017 American Academy of Neurology Annual Meeting. April 22-28, 2017; Boston, MA.
- French J, Thiele E, Mazurkiewicz-Beldzinska M, et al. Cannabidiol (CBD) significantly reduces drop seizure frequency in Lennox‑Gastaut syndrome (LGS): results of a multi-center, randomized, double‑blind, placebo controlled trial (GWPCARE4). Presented at: 2017 American Academy of Neurology Annual Meeting. April 22-28, 2017; Boston, MA.