Long-term Impact of Cenobamate on Cognition in Patients with Drug-Resistant Focal Epilepsy: Outcomes from an...

Cognitive adverse events are a common issue in patients receiving later-generation antiseizure medications (ASMs). In this study, we assessed the long-term effects of cenobamate on cognitive endpoints in patients with drug-resistant focal epilepsy.

In this retrospective, observational study, the clinical records of adult patients who received cenobamate as part of the Spanish Expanded Access Program were reviewed. Seizure frequency, concomitant ASM usage, and data from 20 neuropsychological tests were collected at 6 and 18 months after cenobamate initiation.

Among 14 patients included in the study, eight (57%) had daily seizures at baseline, three (21%) had seizures at least weekly, and three (21%) had seizures at least monthly. The median number of prior ASMs was 10; the median number of concomitant ASMs was three. The median cenobamate dose was 12.5 mg/day at baseline, 200 mg/day at month 6, and 250 mg/day at month 18. At month 18, 10 patients (71%) had at least a 50% reduction in seizure frequency, seven (50%) had at least a 90% reduction, and two (14%) achieved seizure freedom. Significant improvements in cognitive scores from baseline to month 18 were observed for verbal episodic memory (two measures; p = 0.016 and p = 0.0013), visuospatial episodic memory (p = 0.014), and processing speed (p = 0.0018). The mean number of concomitant ASMs (p = 0.0018) and the concomitant ASM drug load (p = 0.0001) decreased significantly between baseline and month 18. The sum of the ratios of prescribed daily dose/daily defined dose (total ratio of defined daily dose) for all concomitant ASMs (p < 0.0001), for perampanel (p = 0.017), and for sodium channel blockers (p = 0.0003) also decreased between baseline and month 18.

In this exploratory, real-world study, we observed significant improvements in seizure frequency, concomitant ASM usage, and cognition at up to 18 months of cenobamate treatment in patients with drug-resistant focal epilepsy.