Positioning Cenobamate in the Treatment Algorithm of Focal Epilepsy: Seizure Control and Benefits Beyond Seizures

This work integrates the opinion on the current use of cenobamate (CNB) of an expert panel structured across seven thematic domains: efficacy, patient profiles, titration and dosing, pharmacokinetic interactions, safety, parallel effects, and therapeutic positioning. According to personal experience and scientific evidence, experts unanimously regarded CNB as likely more efficacious than other newer-generation antiseizure medications (ASMs), particularly based on the long-term sustained seizure-freedom rates, despite the absence of comparative head-to-head studies. Priority candidates are patients with focal epilepsy failing two or more ASMs, including older patients, with a clear inclination toward earlier introduction. Initial response is expected at 100-200 mg/day, although maintenance is typically 200 mg/day or higher, alongside reduction of concomitant ASMs particularly sodium channel blockers and benzodiazepines. The most relevant drug-drug interaction is with clobazam, which may have a synergistic efficacy effect and in parallel increases plasma concentrations of clobazam, thereby inducing adverse events. The most frequent adverse events (somnolence, dizziness, fatigue) are dose-dependent and are reduced by anticipatory reduction of concomitant medication. Beyond seizure reduction, an early intervention with CNB may modify the prognosis of epilepsy, reducing the long-term mortality risk, cognitive impairment, or psychiatric disorders. The panel converged on a priority to position CNB as a third-line treatment in the focal epilepsy treatment algorithm owing to its high efficacy, which will probably lead to modification of the long-term global outcomes of people with epilepsy.