Eslicarbazepine acetate was effective when used as an add-on treatment for patients with drug-resistant focal epilepsy, according to authors of a Cochrane review published in Cochrane Database Systematic Reviews.
While most patients with epilepsy have a good prognosis, up to 30% of patients with epileptic seizures have drug-resistant epilepsy, which can adversely impact their psychosocial, psychiatric, and medical status. Eslicarbazepine acetate, an antiepileptic drug that blocks voltage-gated sodium channels, has been suggested to reduce seizure frequency in these patients.
The objective of the current updated version of a Cochrane Review originally published in 2011 was to determine the efficacy and tolerability of eslicarbazepine acetate when used in combination with other medications for patients with drug-resistant focal epilepsy.
The updated review included studies published from the date of the previous search (November 2011) to 6 December 2016. It aimed to include randomized controlled trials (RCTs), double-blind trials, placebo-controlled trials, and parallel-group or crossover studies of patients with drug-resistant focal epilepsy, defined as continued seizures despite treatment with 1 or more antiepileptic drugs.
The primary outcomes were a 50% or greater reduction in seizure frequency and the proportion of patients with complete cessation of seizures from the time of randomization to the trial conclusion. Secondary outcomes included treatment withdrawal, adverse effects, and drug interactions.
The review included 5 RCTs with 1799 participants aged 16 to 77 years. Of these 5 studies, 4 were included in the previous version of this review and 1 study was added to the analysis. The included studies had treatment periods ranging from 12 to 14 weeks.
An intention-to-treat analysis, pooling all doses of eslicarbazepine acetate, showed that patients treated with eslicarbazepine acetate were significantly more likely to achieve 50% or greater reduction in seizure frequency (relative risk [RR], 1.71; 95% CI, 1.42-2.05). The treatment efficacy was higher with increasing doses, ranging from 22% in patients who received eslicarbazepine acetate at 400 mg/day (RR, 1.22; 95% CI, 0.80-1.85) to 66% in the group that received 800 mg/day (RR, 1.66; 95% CI, 1.34-2.07) to 92% in those treated with a daily dose of 1200 mg (RR, 1.92; 95% CI, 1.56-2.37).
The data also showed that treatment with eslicarbazepine acetate was significantly associated with freedom from seizure (RR, 2.90; 95% CI, 1.49-5.68). While eslicarbazepine acetate at a daily dose of 400 mg was not significantly associated with freedom from seizure, both the 800-mg dose (RR, 3.42; 95% CI, 1.38-8.46) and 1200-mg dose (RR, 3.46; 95% CI, 1.40-8.54) were associated with a seizure-free state.
Compared with placebo, patients treated with eslicarbazepine acetate appeared to be more likely to discontinue treatment due to adverse effects, (overall RR across any dose, 2.66; 95% CI, 1.42-4.96.
Dizziness (RR, 2.81; 99% CI, 1.86-4.27), nausea (RR, 2.61; 99% CI, 1.36-5.01), vomiting (RR, 3.30; 99% CI, 1.34-8.13), somnolence (RR, 1.71; 99% CI, 1.11-2.63), and diplopia (RR, 4.14; 99% CI, 1.74-9.84) were significantly more likely to occur in the group treated with eslicarbazepine acetate, especially at higher doses.
While there were no major potential biases in the review process, the researchers cited the lack of children in the currently evaluated studies as an important limitation.
“Moderate quality evidence provided by this review demonstrates that both ESL [eslicarbazepine acetate] 800 mg and 1200 mg taken once daily can significantly reduce seizure frequency in adults with treatment resistant focal epilepsy, in the short term,” the researchers concluded.
Chang XC, Yuan H, Wang Y, Xu HQ, Hong WK, Zheng RY. Eslicarbazepine acetate add-on therapy for drug-resistant focal epilepsy. Cochrane Database Syst Rev. Published online June 22, 2021. doi:10.1002/14651858.CD008907.pub4