Brivaracetam in Refractory Epilepsy: Mechanism, Tolerability, and Clinical Positioning

Abstract: Epilepsy is a common neurological disorder and has a considerable global impact. Established treatment options remain limited, as current antiseizure medications (ASMs) often do not adequately reduce the frequency of seizures. The standard of care for individuals with epilepsy using existing ASMs often fails to meet both the expectations of clinicians and patients. We observed that many ASMs are linked with a wide range of Adverse Events (AEs). Typically, multiple ASMs are administered to treat refractory epilepsy, but combination therapies can create unfavorable Drug-Drug Interactions (DDIs). An ideal ASM should meet several key criteria: it should effectively treat multiple types of epilepsy, induce minimal AEs to ensure good tolerability and long-term safety, be able to avoid clinically significant DDIs that require dose adjustments, and improve the quality of life of individuals living with epilepsy. Brivaracetam (BRV) is a selective, high-affinity ASM that specifically targets the synaptic vesicle protein 2A ligand. It exhibits greater drug permeability, selectivity, and binding affinity when compared with its structural predecessor, levetiracetam, which leads to more efficient brain penetration. Owing to a faster onset of action, BRV shows better anticonvulsant activity. Reported AEs associated with BRV are generally minor, nonspecific, transient, and manageable. BRV does not affect cytochromes P450 or P-glycoprotein. As a result, it minimizes the likelihood of DDIs that may occur between multiple ASMs or when ASMs are co-administered with pharmacological classes such as antipsychotics, anticoagulants, and antibiotics. When BRV is administered along with other drugs, consider carefully to prevent poten-tial DDIs. BRV is considered a supplemental therapy for refractory focal seizures, as suggested by most experts. Recent studies have demonstrated that BRV monotherapy can offer advantages such as good tolerability, high retention rates, safety, and improved seizure control. This narrative review aimed to synthesize the current preclinical and clinical evidence. We hope to provide a detailed overview of BRV, including its pharmacological properties, safety profile, and therapeutic relevance in the management of refractory epilepsy.