The Effectiveness of Cenobamate in Patients Treated With Vagus Nerve Stimulation for Drug Resistant Epilepsy

Vagus Nerve Stimulation (VNS) is an effective neuromodulatory treatment for drug-resistant epilepsy (DRE), but many patients still experience uncontrolled seizures. These patients, who are highly refractory, may benefit from novel anti-seizure medications (ASM). This study evaluates the effectiveness of cenobamate (CNB) in patients previously or currently treated with VNS.

We reviewed the medical history of all patients treated with VNS at Ghent University Hospital and HUB-Hôpital Erasme Brussels from 1995 to 2024. Patients who received CNB after ≥ 12 months of VNS therapy were included. Mean monthly seizure frequency was assessed before VNS, after VNS, and post-CNB initiation.

Among 620 patients treated with VNS between March 1995 and November 2023, 54 were additionally treated with CNB after a median VNS duration of 9 years. With VNS, seizure frequency data were available for 52 patients. Of these, 13 (25%) achieved a ≥ 50% reduction in seizure frequency at maximum follow-up, but none became seizure-free. After CNB addition (median dose 200 mg, median follow-up 10 months), 24/54 (44.4%) experienced a ≥ 50% reduction in seizures. 6/54 patients (11.1%) reported seizure freedom for a median of 26 weeks. In 20/54 patients (37%), the number of ASMs was reduced. 7/54 (13%) discontinued CNB because of side effects, with fatigue being the most common, in 23/54 patients (42.6%).

For DRE patients treated with VNS who could benefit from further improvement in seizure control, adding CNB is useful. In our cohort, over one-third of patients experienced a meaningful improvement in seizure frequency with this recently marketed ASM.