Cannabidiol decreases frequency of drop seizures in Lennox-Gastaut syndrome

By Naveed Saleh, MD, MS, for MDLinx
Published June 26, 2018

Key Takeaways

The addition of cannabidiol to antiepileptic treatment regimens in children and adults with Lennox-Gastaut syndrome decreased the number of drop seizures they experienced, according to a recent article in the New England Journal of Medicine.

“Cannabidiol has been used for treatment-resistant seizures in patients with severe early-onset epilepsy,” wrote primary author, Orrin Devinsky, MD, New York University Langone Comprehensive Epilepsy Center, New York, NY. “We investigated the efficacy and safety of cannabidiol added to a regimen of conventional antiepileptic medication to treat drop seizures in patients with the Lennox-Gastaut syndrome, a severe developmental epileptic encephalopathy.”

Drop seizures result from an increase or decrease in motor tone and can cause severe injury. Currently, six drugs are approved to treat seizures in patients with Lennox-Gastaut syndrome. Even with treatment, however, most patients continue to experience disabling seizures.

Researchers have shown that cannabidiol decreases the frequency of seizures in animal models with epilepsy. Furthermore, a randomized, controlled trial indicated that cannabidiol decreased the number of seizures in children and young adults with another type of developmental epileptic encephalopathy, Draver syndrome.

Dr. Devinsky and colleagues recruited 225 patients from 30 health centers in this phase 3, multicenter, randomized, double-blind, placebo-controlled trial. The participants were aged between 2 and 55 years, had an electroencephalogram pathognomonic for Lennox-Gastaut syndrome, and experienced at least two types of generalized seizures such as drop seizures for at least 6 months.

Patients in this trial were mostly white and 30% were aged 18 years and older. They were taking a median of three drugs at the time the trial started, with 49% taking clobazam. In all groups, the median number of drop seizures during the 28-day baseline period was 85.

The researchers randomized 76 subjects to a 20-mg cannabidiol group (20 mg/kg/d), 73 subjects to a 10-mg cannabidiol group (10 mg/kg/d), and 76 to a placebo group. The cannabidiol and placebo were prescribed twice daily and taken by mouth. 

The trial lasted for 24 weeks, which included escalation, maintenance, and tapering periods, followed by a 4-week follow-up for safety after discontinuation. Patients or their caregivers recorded the number and type of seizures occurring each day (including drop seizures); use of cannabidiol or placebo; use of other medications; and any adverse events. The patients met with clinicians at 2, 4, 8, and 14 weeks after randomization.

The primary outcome for this study was the percent change from baseline in the number of drop seizures during the duration of treatment.

From baseline, the 20-mg cannabidiol group experienced 41.9% fewer seizures (P=0.005), the 10-mg cannabidiol group 37.2% fewer seizures (P=0.002), and the placebo group 17.2% fewer seizures. Estimated median difference in seizure reduction between the 20-mg and the placebo group was 21.6 percentage points (95% CI: 6.7-34.8; P=0.005), and between the 10-mg and placebo group, 19.2 percentage points (95% CI: 7.7-31.2; P=0.002).

Researchers observed at least a 50% reduction from baseline in drop-seizure frequency in 39% of patients in the 20-mg cannabidiol group, 36% in the 10-mg group, and 14% in the placebo group.

“Significant results in favor of cannabidiol were also seen in secondary outcome measures of at least a 50% reduction in the frequency of drop seizures, the reduction in the frequency of all seizures, and improvement in overall condition,” wrote the researchers.

Encouragingly, patients in the experimental group who were taking clobazam more commonly needed lower doses of this antiepileptic medication than patients in the placebo group. Moreover, of the 212 patients who finished the trial, 210 (99%) went on to enroll in the open-label extension trial.

The most frequent adverse events were somnolence, decreased appetite, and diarrhea, which mostly occurred in the 20-mg cannabidiol group. Overall, six patients dropped out of the 20-mg cannabidiol group and one patient dropped out of the 10-mg cannabidiol group secondary to adverse events. Notably, 14 patients (9%) demonstrated elevated liver enzymes in the experimental groups.

“Among children and adults with the Lennox-Gastaut syndrome, the addition of cannabidiol at a dose of 10 mg or 20 mg per kilogram per day to a conventional antiepileptic regimen resulted in greater reductions in the frequency of drop seizures than placebo,” concluded the researchers.

This study was supported by GW Pharmaceuticals.

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