Royal College of Surgeons in Ireland
Adjunctive cenobamate in highly active and ultra-refractory focal epilepsy.....pdf (1.36 MB)
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Adjunctive cenobamate in highly active and ultra-refractory focal epilepsy: A "real-world" retrospective study

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posted on 2023-03-23, 14:22 authored by Javier Peña-Ceballos, Patrick MoloneyPatrick Moloney, Tudor Munteanu, Michael DoyleMichael Doyle, Niamh Colleran, Brenda Liggan, Annette BreenAnnette Breen, Sinead Murphy, Hany El-NaggarHany El-Naggar, Peter Widdess-Walsh, Norman DelantyNorman Delanty

Objective: Recent clinical trials have shown that cenobamate substantially improves seizure control in focal-onset drug-resistant epilepsy (DRE). However, little is known about cenobamate's performance in highly active (≥20 seizures/month) and ultra-refractory focal epilepsy (≥6 failed epilepsy treatments, including antiseizure medications [ASMs], epilepsy surgery, and vagus nerve stimulation). Here, we studied cenobamate's efficacy and tolerability in a "real-world" severe DRE cohort.

Methods: We conducted a single-center retrospective analysis of consecutive adults treated with cenobamate between October 2020 and September 2022. All patients received cenobamate through an Early Access Program. Cenobamate retention, seizure outcomes, treatment-emergent adverse events, and adjustments to concomitant ASMs were analyzed.

Results: Fifty-seven patients received cenobamate for at least 3 months (median duration, 11 months). The median cenobamate dose was 250 mg/day (range 75-350 mg). Baseline demographics were consistent with highly active (median seizure frequency, 60/month) and ultra-refractory epilepsy (median previously failed ASMs, nine). Most (87.8%) had prior epilepsy surgery and/or vagus nerve stimulation. Six patients stopped cenobamate due to lack of efficacy and/or adverse events. One patient died from factors unrelated to cenobamate. Among patients who continued cenobamate, three achieved seizure freedom (5.3% of cohort), 24 had a 75%-99% reduction in seizures (42.1% of cohort), and 16 had a 50%-74% reduction (28.1% of cohort). Cenobamate led to abolition of focal to bilateral tonic-clonic seizures in 55.6% (20/36) of patients. Among treatment responders, 67.4% (29/43) were treated with cenobamate doses of ≥250 mg/day. Three-fourths of patients reported at least one side-effect, most commonly fatigue and somnolence. Adverse events most commonly emerged at cenobamate doses of ≥250 mg/day. Side-effects were partially manageable by reducing the overall ASM burden, most often clobazam, eslicarbazepine, and perampanel.

Significance: Patients with highly active and ultra-refractory focal epilepsy experienced meaningful seizure outcomes on cenobamate. Emergence of adverse events at doses above 250 mg/day may limit the potential for further improvements in seizure control at higher cenobamate doses.


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Published Citation

Peña-Ceballos J. et al. Adjunctive cenobamate in highly active and ultra-refractory focal epilepsy: A "real-world" retrospective study. Epilepsia. 2023;64(5):1225-1235.

Publication Date

15 February 2023

PubMed ID



  • Beaumont Hospital
  • FutureNeuro Centre
  • School of Pharmacy and Biomolecular Sciences


Blackwell Science


  • Published Version (Version of Record)