Brivaracetam as viable monotherapy option for focal and generalized epilepsy

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.