JAMA Neurol

Cenobamate shows strongest real world effectiveness in drug resistant focal epilepsy

February 16, 2026

In a pooled analysis of 1,949 adults with drug‑resistant focal epilepsy, cenobamate demonstrated markedly higher odds of achieving a ≥50% seizure reduction at 6 months than brivaracetam (odds ratio [OR], 0.18; 95% confidence interval [CI], 0.12–0.28), perampanel (OR 0.26; 95% CI, 0.16–0.42), and lacosamide (OR, 0.29; 95% CI, 0.17–0.49). Twelve‑month findings were consistent, with cenobamate also outperforming comparators on responder and seizure‑freedom outcomes. Cenobamate was associated with the highest adverse‑effect rate (57.8%), while lacosamide had the lowest (14.8%). Treatment retention at 12 months was higher with cenobamate compared with brivaracetam (OR, 0.43) and perampanel (OR, 0.56); there was no significant difference vs. lacosamide.

Clinical takeaway: When selecting adjunctive therapy for drug‑resistant focal epilepsy, cenobamate may offer superior seizure reduction, but clinicians should weigh its higher side‑effect burden against individual patient tolerability and treatment goals.

Source:

Cerulli Irelli E, et al; Comparative REal-World Evidence (CREW) Study Group. (2026, February 9). JAMA Neurol. Comparative Effectiveness of Brivaracetam, Cenobamate, Lacosamide, and Perampanel in Focal Epilepsy. https://pubmed.ncbi.nlm.nih.gov/41661607/