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Observational Study
. 2025 Aug;46(8):3875-3884.
doi: 10.1007/s10072-025-08174-y. Epub 2025 Apr 15.

Cenobamate as add-on treatment in ultra-refractory focal epilepsy: Real-world results from The Danish Epilepsy Centre, Dianalund, Denmark

Cathrine E Gjerulfsen  1   2 , Stefan Juhl  3 , Katarzyna M Mieszczanek  3 , Lucie Spanilá  3 , Kristin S Thygesen  3 , Agnieszka Pavbro  3 , Rikke S Møller  1   2 , Guido Rubboli  4   5   6
Affiliations
Observational Study

Cenobamate as add-on treatment in ultra-refractory focal epilepsy: Real-world results from The Danish Epilepsy Centre, Dianalund, Denmark

Cathrine E Gjerulfsen et al. Neurol Sci. 2025 Aug.

Abstract

Objectives: At The Danish Epilepsy Centre, Dianalund, Denmark, we aimed to assess the long-term efficacy, tolerability profile, and influence on concomitant antiseizure medications (ASMs) of cenobamate as an add-on treatment in patients with ultra-refractory focal epilepsies.

Methods: Adult patients with ultra-refractory epilepsy (defined as focal epilepsies in which ≥ 6 treatments, including ASM trials, epilepsy surgery, and vagus nerve stimulator, failed to achieve seizure control) treated with add-on cenobamate between October 2021 and June 2024 were included in our retrospective, observational study. Data were collected through electronic patient records and seizure-diaries.

Results: 32 patients were included. The mean length of treatment was 21 months (range 2-32 months) and the median dose of cenobamate was 250 mg (range 50-400 mg). Fourteen/32 (44%) patients were responders (≥ 50% reduction in seizure frequency) to cenobamate, including five patients who became seizure-free (15.6% of the total cohort). Eleven/32 (34%) discontinued due to adverse effects (AEs) or lack of efficacy. Patients with active focal-to-bilateral-tonic-clonic seizures remaining on treatment decreased by 50%. The ASM most frequently reduced was lacosamide, while the one most often discontinued was lamotrigine. Fifteen/32 (47%) patients reported at least one AE during the treatment period of 32 months. Two-thirds were resolved by dose-reduction of ASMs or cenobamate. AEs most frequently reported were tiredness and dizziness; the lowest incidence of these AE was found when cenobamate was added as the third drug.

Significance: Our study underlines the usefulness of cenobamate in treating patients with ultra-refractory epilepsy and indicates its long-term effectiveness in real-world clinical practice.

Keywords: Anti-seizure medication; Cenobamate; Drug-resistant epilepsy; Focal epilepsy; Refractory.

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Conflict of interest statement

Declarations. Informed consent: Informed consent was obtained from all individual participants included in the study. Ethics approval: Ethical approval was waived by the local Ethics Committee of The Danish Epilepsy Center, Filadelfia, Dianalund, Denmark, in view of the retrospective nature of the study and all the procedures being performed were part of the routine care. Competing interests: GR has received speaker fees from Angelini Pharma and UCB Pharma and participated to advisory boards meetings of Angelini Pharma and UCB Pharma. RSM has received consulting fees from UCB Pharma, Orion, Saniona, and Immedica, and speaker fees from EISAI, Angelini Pharma, Jazz Pharmaceuticals, Orion, and UCB Pharma. CEG has received funding for research and speaker honoraria from UCB Pharma. None of the authors has recent, present, or anticipated employment by any organization that may gain or lose financially through the publication of the manuscript, nor any financial or non-financial interests to disclose.

Figures

Fig. 1
Fig. 1
The distribution of responders and the retention of patients treated with cenobamate in the study period lasting from October 2021 to June 2024. The percentage distribution of response to add-on treatment with cenobamate in our cohort of 32 patients is also illustrated
Fig. 2
Fig. 2
Responders among patients with baseline seizure frequencies at ≤ 5 per month, at ≤ 5 and ≤ 10 per month, and > 10 per month, with seizures divided into different types according to the latest ILAE classification proposals [1]
See this image and copyright information in PMC

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