Cognitive Effects of Cenobamate as Compared to Perampanel: A Cross-Sectional Multicentre Study in 600 Patients.

Authors

Juri-Alexander Witt, Judit Catalán-Aguilar, Elisa Schütz, Randi von Wrede, Kevin G Hampel, Yulia Novitskaya, Rainer Surges, Mercedes Garcés, Birgitta Metternich, Kathrin Wagner, Vicente Villanueva, Christoph Helmstaedter

Published in

CNS drugs. Oct 02, 2026. Epub Oct 02, 2026.

Abstract

To date, no study has evaluated the objective cognitive effects of cenobamate (CNB) using an independent comparator group.
To compare cognitive performance in individuals with epilepsy treated with CNB versus perampanel (PER), an antiseizure medication (ASM) without systematic negative effects on objective cognitive performance.
This retrospective cross-sectional multicentre study provides a comparative analysis of cognitive performance in patients with epilepsy treated with CNB versus PER. The cognitive assessment focused on executive functions (EpiTrack^®). A Bayesian analysis of variance (ANOVA) was conducted to evaluate cognitive performance with treatment type and number of concomitant ASMs as fixed factors.
The analysis included 600 individuals with epilepsy (mean age: 38.7 ± 12.9 years, 48.5% women), 200 of them with CNB (mean dose: 190.9 ± 94.1 mg/day; range 12.5-450.0) and a matched sample (sex, age, age at epilepsy onset, education) of 400 patients with PER (mean dose: 7.1 ± 3.0 mg/day; range 2.0-12.0). ANOVA indicated no difference in cognitive performance between patients treated with CNB versus PER (Bayes Factor [BF] = 0.207) but decisive evidence of a negative effect of more concomitant ASMs (BF = 9.5 × 10⁶).
The study demonstrated comparable performance in executive functions in individuals treated with CNB or PER and confirmed the adverse effect of an increasing number of combined ASMs. This appears consistent with previous studies showing mostly stable performance after introduction of CNB. Our study was not suited to address previously claimed dose-dependent cognitive side effects and did not assess episodic memory.

PMID:
42827227
Bibliographic data and abstract were imported from PubMed on 03 Oct 2026.

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