A review of the pharmacology and clinical efficacy of brivaracetam
Open accessAbstract
Brivaracetam (BRV; Briviact) is a new antiepileptic drug (AED) approved for adjunctive treatment of focal (partial-onset) seizures in adults. BRV is a selective, high-affinity ligand for synaptic vesicle 2A (SV2A) with 15- to 30-fold higher affinity than levetiracetam, the first AED acting on SV2A. It has high lipid solubility and rapid brain penetration, with engagement of the target molecule, SV2A, within minutes of administration. BRV has potent broad-spectrum antiepileptic activity in animal models. Phase I studies indicated BRV was well tolerated and showed a favorable pharmacokinetic profile over a wide dose range following single (10-1,000 mg) and multiple (200-800 mg/day) oral dosing. Three pivotal Phase III studies have demonstrated promising efficacy and a good safety and tolerability profile across doses of 50-200 mg/day in the adjunctive treatment of refractory focal seizures. Long-term data indicate that the response to BRV is sustained, with good tolerability and retention rate. BRV is highly effective in patients experiencing secondarily generalized tonic-clonic seizures. Safety data to date suggest a favorable psychiatric adverse effect profile in controlled studies, although limited postmarketing data are available. BRV is easy to use, with no titration and little drug-drug interaction. It can be initiated at target dose with no titration. Efficacy is seen on day 1 of oral use in a significant percentage of patients. Intravenous administration in a 2-minute bolus and 15-minute infusion is well tolerated. Here, we review the pharmacology, pharmacokinetics, and clinical data of BRV.
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Padsevonil and related ligands extend this pharmacology with optimized SV2A engagement and limited drug interaction profiles.
“Padsevonil and related ligands extend this pharmacology with optimized SV2A engagement and limited drug interaction profiles, positioning the class for chronic adjunctive use where synaptic resilience and clean tolerability are essential [175,219,220].”
From Synaptic Plasticity—Intrinsic Excitability and Antidepressant Discovery (2026) · cites this paper as [219]
The Mode of action section describes brivaracetam as a high-affinity SV2A ligand, and the Drug–drug interactions section reports limited interactions with many concomitant drugs. Those passages support the claim for brivaracetam, but our copy does not establish padsevonil’s SV2A engagement or drug-interaction profile. Page numbers were not available in the indexed passages. (LLM, conf=0.83)
Experimental — accuracy not yet measuredBrivaracetam provides higher SV2A affinity, faster brain entry, and robust target occupancy, attributes that may consolidate network gains established by agents such as ketamine and reduce relapse risk.
“Brivaracetam provides higher SV2A affinity, faster brain entry, and robust target occupancy, attributes that may consolidate network gains established by agents such as ketamine and reduce relapse risk through sustained vesicle cycling competence and dampening of pathological glutamate release [175,200,201,219].”
From Synaptic Plasticity—Intrinsic Excitability and Antidepressant Discovery (2026) · cites this paper as [219]
The Mode of action section reports that brivaracetam has 15- to 30-fold higher SV2A affinity than levetiracetam, and the Preclinical profile and Conclusion describe rapid brain entry and SV2A occupancy. The paper does not support the proposed link to ketamine-established network gains or reduced relapse risk through sustained vesicle cycling and dampened pathological glutamate release; it says the details of SV2A binding’s anticonvulsant effect remain unknown. No page numbers were supplied for these passages. (LLM, conf=0.91)
Experimental — accuracy not yet measuredBrivaracetam may show improved behavioral tolerability in some patients, and switching within the class is feasible when adverse effects emerge.
“Brivaracetam may show improved behavioral tolerability in some patients, and switching within the class is feasible when adverse effects emerge, enabling continuity of presynaptic stabilization [219,225].”
From Synaptic Plasticity—Intrinsic Excitability and Antidepressant Discovery (2026) · cites this paper as [219]
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- Authors
- Klein, P., Diaz, A., Gasalla, T., & Whitesides, J.
- Affiliations
- Mid Atlantic Epilepsy and Sleep Center (US)
- UCB Pharma (United States) (US)
- UCB Pharma (Germany) (DE)
- Corresponding author
- Klein, Pavel
- ORCID
- Klein, Pavel
- Venue
- Clinical Pharmacology: Advances and Applications
- Publisher
- Informa UK Limited
- Published
- 2018-01
- Volume
- Volume 10
- Pages
- 1-22
- ISSN
- 1179-1438 (ISSN-L)
- PMC
- PMC5783144
- OpenAlex
- W2783522776
- Cited by
- 99
- References
- 84
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 14 · 2023: 7 · 2022: 14 · 2021: 17 · 2020: 15 · 2019: 10 · 2018: 8
- FWCI
- 1.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Clinical Pharmacology Advances and Applications (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Funders
- UCB Pharma
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Health Sciences › Medicine › Physiology › Diet and metabolism studies
- Keywords
- brivaracetam, antiepileptic drugs, focal seizures, drug-resistant epilepsy, adjunctive therapy, pharmacokinetics, drug safety and tolerability, secondarily generalized tonic-clonic seizures, psychiatric adverse effects, drug-drug interactions, intravenous administration
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