Brivaracetam as viable monotherapy option for focal and generalized epilepsy

Antiseizure monotherapy is the gold standard of early epilepsy care. We investigated whether Brivaracetam (BRV), a high-affinity SV2A ligand, approved in Europe only as adjunctive therapy for focal epilepsy, may represent a useful monotherapy option in routine clinical practice with regard to seizure reduction and tolerability.

We retrospectively analyzed 157 adult patients treated with BRV monotherapy between 2016 and 2025 at the Freiburg Epilepsy Center. Patients received BRV as first-line therapy (n = 16), after reduction from polytherapy (n = 30), or after conversion from levetiracetam (LEV; n = 98) or other ASM (n = 13). Outcomes at 6, 12, and 24 months included seizure freedom, responder rates, retention, adverse events (AEs), and dose-response.

Overall, 44% of patients achieved seizure freedom (≥6 consecutive months) at any time during follow-up. Responder rate was 79% after 6 months, and retention rate was 64% at 6 months yet declined to 29% at 24 months. Favorable seizure outcomes were observed across different treatment settings. Patients converted from LEV showed particularly high rates of seizure freedom (52% at 6 months) and frequent improvement in tolerability (79.6%). Good seizure control was achieved already at dosages of up to 50 mg/d. Tolerability was often improved following BRV introduction; only 1.9% of patients experienced newly emerging AEs, whereas 92% of pre-existing AEs resolved after switching to BRV monotherapy. AEs occurred in 22.4% of patients and predominantly consisted of mild psychiatric or sleep-related symptoms.

In this retrospective real-world cohort, BRV monotherapy was associated with favorable short-term seizure outcomes and good tolerability. Particularly favorable outcomes were observed after conversion from LEV. Although long-term retention decreased over time, a substantial proportion of patients continued to benefit from BRV monotherapy over a two-year period, despite BRV being the initial monotherapy in only 25% of the cohort. Overall, these findings suggest that BRV may represent an effective and well-tolerated monotherapy option for selected patients and provide support for further prospective studies evaluating its role in both focal and generalized epilepsies.