Cenobamate in older adults with drug-resistant epilepsy: Real-world tolerability, efficacy, and predictors of discontinuation.

PURPOSE: Cenobamate (CNB) is highly efficacious for focal-onset seizures, but real-world data in older adults (≥60 years) remain scarce. This study evaluates the tolerability, efficacy, and dosing patterns of CNB in this population to guide clinical decision-making.

METHODS

We conducted a retrospective cohort study of patients aged ≥60 years with drug-resistant epilepsy initiated on CNB. The primary outcome was tolerability, defined as treatment continuation versus discontinuation due to adverse effects (AEs). Secondary outcomes included ≥50% seizure reduction and seizure freedom. Predictors of tolerability-related discontinuation were assessed using multivariable analysis.

RESULTS

Among 75 included patients, 61 (81.3%) continued CNB at last follow-up. Discontinuation due to AEs occurred in 10 patients (13.3%). Among the total cohort, 69.3% achieved a ≥ 50% seizure reduction and 64.0% reached seizure freedom. The mean peak dose achieved was 197.3 mg/day. In multivariable analysis, higher Charlson Comorbidity Index (CCI) score (adjusted OR = 1.26, 95% CI 0.89-1.78, p = 0.025) and greater number of concomitant CNS-active non-ASM medications (adjusted OR = 1.27, 95% CI 0.93-1.72, p = 0.013) were statistically significant predictors of tolerability discontinuation. Patients aged ≥70 years were more likely to discontinue earlier due to adverse effects than those aged 60-69 (p = 0.007). Additionally, a significant inverse association was observed between age and peak CNB dose (ρ = -0.285, p = 0.013).

CONCLUSION

CNB is effective and generally well-tolerated in older adults, with most reaching therapeutically meaningful doses. However, an elevated comorbidity burden and advancing age (≥70 years) increase the risk of discontinuation due to adverse effects, underscoring the need for individualized, cautious titration in this vulnerable population.