Cenobamate in super-refractory status epilepticus: current evidence from a patient-level synthesis

Abstract

Super-refractory status epilepticus (SRSE) represents a challenging neurological emergency, with limited therapeutic options after conventional intravenous antiseizure medications (ASMs) and continuous anesthetic therapy have failed. Cenobamate has shown remarkable efficacy in drug-resistant focal epilepsy, but its role in SRSE is currently supported only by isolated case reports. We performed a patient-level synthesis of published cases of cenobamate-treated SRSE, focusing on treatment latency, titration strategy, electroclinical response, concomitant therapies, safety, and functional outcomes. Three publications reporting six patients were identified. Cenobamate was introduced between 13 and 103 days after SRSE onset, following failure of multiple intravenous and oral ASMs, anesthetic agents, and, in most cases, immunomodulatory therapies. Although the timing of treatment initiation varied substantially, electroencephalographic improvement generally occurred within two weeks after cenobamate initiation and was usually accompanied by clinical recovery, successful withdrawal of anesthetic therapy, and liberation from the intensive care unit. Most patients initiated cenobamate at the recommended dose of 12.5 mg/day but underwent individualized dose-escalation schedules compared with the approved outpatient regimen. No cases of drug reaction with eosinophilia and systemic symptoms, severe cardiac adverse events, or treatment discontinuation attributable to cenobamate were reported. Although the available evidence remains limited to a small number of observational reports, this patient-level synthesis identified consistent clinical patterns that support further investigation of cenobamate as an adjunctive therapy for SRSE. At present, no conclusions regarding treatment efficacy can be drawn. Prospective multicenter studies are needed to clarify cenobamate optimal timing, titration strategy, safety, and potential role within SRSE treatment algorithms.