A review published in the Cochrane database of systematic reviews revealed that carisbamate might be effective with good tolerability in people having drug‐resistant focal epilepsy. Chuansen Lu et al. undertook this study to investigate the tolerability and effectiveness of carisbamate (a drug that suppresses voltage-gated sodium channels) when utilized as an add-on treatment for epilepsy.

Databases such as MEDLINE and Cochrane Register of Studies (includes randomized or quasi-randomized controlled trials [RCTs] from Embase, ClinicalTrials.gov, World Health Organization-International Clinical Trials Registry Platform, PubMed, the Cochrane Central Register of Controlled Trials, and the specialized registers of Cochrane review groups including epilepsy) were searched.

The study authors also examined the ongoing trials registers and reference lists and contacted the authors of the incorporated trials. Double-blind RCTs with parallel-group or cross-over design and evaluating carisbamate versus placebo or another antiepileptic agent, as an add-on treatment for drug-resistant focal epilepsy were included.

Notably, 2 review authors independently chose the trials for inclusion, evaluated trial quality, and extracted the data. A 50% or higher decline in seizure frequency (responder rate) was the major endpoint while the quality of life, seizure freedom, adverse events, and therapy withdrawal (for any reason and due to adverse events) were the secondary endpoints.

Using Mantel-Haenszel statistical method, the data were evaluated according to the intention-to-treat population. The results were presented as risk ratios (RRs) with 95% confidence intervals. The study included 4 RCTs (comparing carisbamate with placebo for drug-resistant focal epilepsy) involving 2211 participants (age above 16 years) that were administered at least 1 other antiepileptic agent concomitantly. Considerable risk of bias was noted across the incorporated trials.

In this study, all 4 trials were at elevated risk of attrition bias due to incomplete reporting of attrition and the elevated treatment withdrawal rates noted, particularly with increased doses. Also, all 4 trials had an unclear risk of detection bias since they did not mention if the outcome assessors were blinded. According to the meta-analysis, carisbamate therapy elicited a higher responder rate in comparison with placebo (RR 1.36).

More number of people in the carsibamate group attained seizure freedom (RR 2.43); withdrew from therapy for any reason (RR 1.32); and withdrew from therapy due to adverse events (RR 1.80) when compared to the placebo group. But, the evidence for the 3 outcomes was very low-certainty. Regarding the percentage of people experiencing at least 1 noxious event, no difference was noted between the treatment groups (RR 1.10).

Compared to the placebo group, more number of people in the carisbamate group reported somnolence (RR 1.82) and dizziness (RR 2.06), but not nausea (RR 1.19), fatigue (RR 1.11), or headache (RR 1.13). The quality of life was not reported by any trial. Additional robust RCTs with a broader range of participants, more clear methodology, long-term follow-up, more clinical outcomes, and more seizure types are warranted.