Brivaracetam in Off-Label Use and Special Populations: A Narrative Review of Current Evidence

Background: Brivaracetam (BRV) is a synaptic vesicle protein 2A (SV2A) ligand approved for the treatment of focal-onset seizures. Its clinical use has increasingly expanded beyond approved indications and into understudied populations. Objective: We aim to review BRV use beyond approved indications and in special populations. Methods: MEDLINE, Embase, and Scopus were searched from inception to 30 April 2026. Eligible clinical studies were selected using prespecified criteria and synthesized narratively. Off-label status was determined separately under FDA and EMA labelling. Results: The evidence consisted predominantly of observational studies, real-world cohorts, case series, and subgroup analyses of randomised trials. In genetic generalized epilepsies (GGE), BRV was associated with seizure reduction in several cohorts, whereas findings in developmental and epileptic encephalopathies (DEEs) were more heterogeneous. Real-world studies demonstrated the feasibility of BRV monotherapy, particularly following transition from levetiracetam. In status epilepticus (SE), intravenous BRV has been associated with SE cessation, although its independent contribution, optimal dose and timing, and role in treatment algorithms remain uncertain. Pregnancy and breastfeeding reports identified no clear safety signal, although exposure and long-term outcome data were scarce. Neonatal evidence was restricted largely to pharmacokinetic and short-term tolerability findings. Observational data indicated that psychiatric or behavioural adverse effects did not recur in some patients switched from levetiracetam; evidence in psychotic disorders remained particularly limited. Conclusions: BRV may be useful in selected off-label settings and special populations. However, evidence remains limited and largely observational, so treatment decisions should be individualized. Prospective controlled studies and dedicated registries are needed.