Thiele EA, et al. - Physicians sought to evaluate the efficacy and safety of cannabidiol as an add-on anticonvulsant therapy in patients with seizures associated with Lennox-Gastaut syndrome. For the treatment of patients with drop seizures associated with Lennox-Gastaut syndrome, add-on cannabidiol was found to be efficacious and generally well tolerated.

Methods

• The physicians performed this randomised, double-blind, placebo-controlled trial at 24 clinical sites in the USA, the Netherlands, and Poland.
• They examined the efficacy of cannabidiol as add-on therapy for drop seizures in patients with treatment-resistant Lennox-Gastaut syndrome.
• For this study, eligible patients (aged 2-55 years) had Lennox-Gastaut syndrome, including a history of slow (<3 Hz) spike-and-wave patterns on electroencephalogram, evidence of more than one type of generalised seizure for at least 6 months, at least 2 drop seizures per week during the 4-week baseline period, and had not responded to treatment with at least 2 antiepileptic drugs.
• They randomly assigned patients (1:1) using an interactive voice response system, stratified by age group, to receive 20 mg/kg oral cannabidiol daily or matched placebo for 14 weeks.
• All patients, caregivers, investigators, and individuals assessing data were masked to group assignment.
• Percentage change from baseline in monthly frequency of drop seizures during the treatment period was the primary endpoint, which was examined in all patients who received at least 1 dose of study drug and had post-baseline efficacy data.
• They included all randomly assigned patients in the safety analyses.

Results

• The physicians randomly assigned 171 patients to receive cannabidiol (n=86) or placebo (n=85) between April 28, 2015, and Oct 15, 2015.
• In the cannabidiol group, 14 patients and in the placebo group, 1 patient discontinued study treatment.
• All randomly assigned patients received at least 1 dose of study treatment and had post-baseline efficacy data.
• The median percentage reduction in monthly drop seizure frequency from baseline in the cannibidiol group was 43·9% (IQR -69·6 to -1·9) and 21·8% (IQR -45·7 to 1·7) in the placebo group.
• During the 14-week treatment period, the estimated median difference between the treatment groups was -17·21 (95% CI -30·32 to -4·09; p=0·0135).
• Adverse events (most were mild or moderate) occurred in 74 (86%) of 86 patients in the cannabidiol group and 59 (69%) of 85 patients in the placebo group.
• Diarrhoea, somnolence, pyrexia, decreased appetite, and vomiting were the most common adverse events.
• Due to adverse events, 12 (14%) patients in the cannabidiol group and 1 (1%) patient in the placebo group withdrew from the study.
• In the cannabidiol group, 1 death (1%) was reported, but this was considered unrelated to treatment.