Cannabidiol shots safe but of no benefit in drug-resistant focal epilepsy

In the treatment of patients with drug-resistant focal epilepsy, transdermally administered cannabidiol is well tolerated but is not superior to placebo in terms of reducing seizure frequency, according to a study.

The study included 188 adult patients (mean age 39.2 years, 54.8 percent female) with drug-resistant focal epilepsy receiving a stable regimen of up to three antiseizure medications seen at 14 epilepsy trial centres across Australia and New Zealand. They were randomized to receive transdermal cannabidiol at 195 mg (n=63) or 390 mg (n=62) or placebo (n=63) twice daily for 12 weeks, after which they could enrol in an open-label extension study for up to 2 years.

Seizure frequency was self-reported using a daily diary. The primary efficacy endpoint was the least squares mean difference in the log-transformed total seizure frequency (reported using a daily diary) per 28-day period over the 12-week treatment period.

Results revealed no significant difference in seizure frequency at week 12 across the three treatment groups: placebo (mean, 2.49 seizures per 28 days), 195-mg cannabidiol (mean, 2.51 seizures per 28 days; least squares mean difference, 0.014, 95 percent confidence interval [CI], −0.175 to 0.203; p=0.89), and 390-mg cannabidiol (mean, 2.59 seizures per 28 days; least squares mean difference, 0.096, 95 percent CI, −0.093 to 0.285; p=0.32).

Six months into the open-label extension, 115 (60.8 percent) of the patients who remained in the study achieved at least a 50-percent reduction in seizure frequency.

Treatment-emergent adverse events (TEAEs) occurred in 63 patients (50.4 percent) in the combined cannabidiol groups and in 26 patients (41.3 percent) in the placebo group, with the rates similar in the cannabidiol groups. The most common TEAEs among cannabidiol-treated patients were headache, fatigue, nausea, dryness and pruritus in injection site, urinary tract infection, and anxiety, among others.

Fourteen out of 188 patients (7 percent) discontinued treatment, and 171 of them (98 percent) continued into the open-label extension.