Cenobamate’s effect on mood and seizure frequency

Objective Real-world experience with efficacy and tolerability of newly approved antiseizure medications (ASM) often diverges from findings in their controlled clinical trials. Cenobamate (CNB), demonstrated a high responder rate and seizure freedom in placebo-controlled trials. Since 40% of patients with epilepsy (PWE) experience comorbid depression, understanding the potential mood-related effects of CNB is critical. This retrospective study evaluates the impact of CNB on mood, tolerability, and seizure control when used as adjunctive therapy at our institution. Methods A single-center retrospective chart review was conducted of adult patients with refractory focal epilepsy who initiated CNB add-on therapy (May 2020–July 2023). We assessed changes in depressive symptoms and seizure frequency. Eligibility required ≥3 months on CNB, seizure frequency available at baseline and last follow-up (events/30 days), and paired Patient Health Questionnaire-9 (PHQ-9) scores. Seizure outcomes were analyzed as paired change (ΔSeizures), as log 2 fold-change, and percent change. We assessed response to treatment by assessing seizure-freedom, as well as ≥50% and ≥75% reduction in seizure frequency. Results 73 adult PWE met study criteria. Median seizure frequency fell from 5 at baseline to 1.5 per 30 days at the last follow-up (p < 0.001), with a 50% median reduction (95% CI: 70%–19%) in seizure frequency within a median of 488 days of follow-up. At the last follow-up, 29% of patients were seizure-free overall. PHQ-9 scores did not worsen (median ΔPHQ-9 = 0 (HL = 0; 95% CI –2 to 0; 0.34), and in multiple linear regressions of ΔPHQ-9, no prespecified covariates were associated with mood outcomes. Conclusion Our findings suggest that CNB is a safe and effective adjunctive ASM that improves seizure control in PWE and that does not significantly change PHQ-9 scores. While better seizure control may mask the drug's potential effects on mood—as reduced seizure burden itself could influence depressive symptoms—its impact on individual mood was variable. These results highlight the need for further research. Simple language summary Patients with epilepsy often experience depression, making it important to assess whether new antiseizure medications affect mood. This study reviewed medical records of patients prescribed cenobamate (Xcopri) between May 2020 and August 2023. The results showed that cenobamate helped improve seizure control, and most patients did not experience a worsening of mood. These findings suggest that cenobamate is a safe option for epilepsy treatment, although further research is needed.