Cenobamate in Generalized Epilepsy and Combined Generalized and Focal Epilepsy.

Background and Objectives: Cenobamate (CNB) is a United States Food and Drug Administration-approved antiseizure medication (ASM) for focal-onset seizures; however, its potential clinical effectiveness as a broad-spectrum ASM is not established. CNB has a proposed dual mechanism of action with preferential blockade of persistent sodium currents and positive allosteric modulation of the γ-aminobutyric acid-A (GABA-A) receptor. We evaluated the efficacy of CNB in drug refractory patients with genetic generalized epilepsies (GGE) or combined generalized and focal epilepsies (CGFE), including developmental and epileptic encephalopathies. Methods: We performed a retrospective review and identified the following: cohort 1 (n = 4) with GGE, of which 2 patients had idiopathic generalized epilepsy, and cohort 2 with CGFE (n = 9), of which 4 patients had Lennox-Gastaut syndrome and 1 had Dravet syndrome. Results: In cohort 1, all 3 patients with frequent generalized tonic-clonic seizures (GTCs) had a greater than 50% reduction in GTCs. In cohort 2, reduction in both generalized and focal-onset seizures was noted. In these groups together, the mean reduction of all seizure types was 58%, and ≥50% responder rate was 70% (SD = ±34.16, median = 50%). No worsening of generalized-onset seizures occurred in either cohort. Seventy-seven percent of patients experienced side effects, warranting a modification of treatment managed by slower titration, dose reduction of CNB, or discontinuing other ASMs. Discussion: In our retrospective case series, CNB seems to be an effective ASM for patients with drug-resistant GGE and CGFE. The ongoing CNB trial assessing effectiveness for primary GTCs will provide more data on generalized-onset seizures. Classification of Evidence: This study provides Class IV evidence that CNB in generalized epilepsy and combined generalized and focal epilepsy reduces seizure frequency.