Cognitive Outcomes During Adjunctive Cenobamate Treatment in Patients with Drug-Resistant Epilepsy: An Interim Analysis of a Prospective Observational Study.

Aim

To examine the impact of cenobamate (CNB) treatment on cognitive function in patients with epilepsy.

Methods

We assessed seventeen patients before (T0) and after treatment (T1) with CNB 200 mg/day (duration: median 5.6 months, range 3.3-11.6 months). All patients underwent a neuropsychological test battery covering verbal functions, attention and processing speed, memory, and executive functions. Serum concentrations of concomitant antiseizure medications were analyzed at T0 and T1, and CNB serum concentrations were analyzed at T1.

Results

Improvements and declines were observed in attention and processing speed, executive functions, and memory, although declines were substantially more frequent. Within the attention domain, most patients (14/17) showed a decline of ≥0.5 SD in at least one test parameter, primarily in short-term and working memory. Verbal memory was predominantly negatively affected, with twelve patients declining by ≥0.5 SD in learning and/or retention. Visual memory showed a contrasting pattern, with improvements being more prevalent than declines. Ten patients declined by ≥0.5 SD in processing speed. Pronounced deteriorations were observed in executive functions, where twelve patients declined by ≥0.5 SD, including nine by ≥1 SD. Cognitive effects did not correlate with CNB serum concentrations.

Conclusion

In this cohort, moderate cognitive deterioration was observed following adjunctive cenobamate treatment at 200 mg/day in a substantial proportion of patients, particularly in attention, verbal memory, processing speed, and executive functions. In contrast, a subset of patients showed improvements, primarily in visual memory and phonemic fluency. These findings highlight the need for individualized cognitive monitoring during CNB treatment.