Brief transmissions from the neural frontier.
This large multicenter real-world study of nearly 2,000 patients with drug-resistant focal epilepsy found cenobamate significantly more effective than brivaracetam, lacosamide, and perampanel for seizure reduction and freedom. Despite higher adverse effect rates, cenobamate showed superior treatment retention, providing practical guidance for ASM selection in refractory cases.
Irelli et al, JAMA Neurol 2026: Comparative Effectiveness of Brivaracetam, Cenobamate, Lacosamide, and Perampanel in Focal Epilepsy. Read the full paper.
Problem: Direct comparative effectiveness data among newer antiseizure medications in drug-resistant focal epilepsy has been limited. This is largely because prospective studies are hard to design and to conduct ethically. Withholding treatment in placebo-controlled trials can often times not be done ethically and for most patients eligible to enrol in such studies, seizures are relatively rare events, leading to a large sample sizes for sufficient statistical power.
Result: Cenobamate demonstrated superior efficacy across all measures (50% response rate, seizure freedom, notably also retention) compared to three other newer ASMs, despite causing more adverse effects.
Open Questions: Prospective head-to-head trials and longer-term safety data are still somewhat necessary to confirm these real-world effectiveness findings and better characterize cenobamate’s risk-benefit profile. For now, all we have to counsel patients is that there are some hints that cenobamate could be more effective in stopping seizures than other modern drugs, and the associated risks may be worth it.
Written on February 22nd , 2026 by Habakuk Hain