To evaluate real-world effectiveness of cenobamate in reducing seizure frequency and to characterize the demographic and clinical profiles of treated patients.

Cenobamate is a recently approved anti-seizure medication for focal epilepsy, demonstrating robust efficacy in randomized controlled trials. However, clinical trial populations often exclude patients with multiple comorbidities or complex risk factors, limiting generalizability. Real-world evidence is essential to understand its effectiveness across diverse demographic groups and clinically challenging cases, including those with psychiatric comorbidities and developmental disorders.

A retrospective cohort study was conducted involving 120 patients with focal epilepsy at a tertiary care center. Demographic data, seizure risk factors, and psychiatric comorbidities were extracted. Seizure frequency was assessed before and after at least one year of cenobamate therapy. Descriptive statistics were calculated, and a Wilcoxon signed-rank test was used to evaluate changes in seizure frequency.

The cohort (mean age 39.4 ± 12.3 years; 53.3% male) was ethnically diverse (White 55%, Black 23.3%, Hispanic 11.7%, Asian 2.5%). Common risk factors included intellectual disability/developmental delay (48.3%), traumatic brain injury (19.2%), and family history (10.8%). Psychiatric comorbidities were frequent, including depression and anxiety. Among 57 patients treated >1 year, mean seizure frequency decreased from 2.5/week (SD 2.06) to 1.7/week (SD 1.3), a statistically significant reduction (W = 1.00, p = 0.0312).

Cenobamate significantly reduced seizure frequency in a real-world, clinically complex population with diverse backgrounds and comorbidities. These findings support its effectiveness beyond clinical trials and highlight the need for prospective studies to assess long-term outcomes and optimize treatment strategies for heterogeneous epilepsy populations.