Recent advances in the pharmacotherapy of epilepsy: brivaracetam and perampanel as broad-spectrum antiseizure drugs for the treatment of epilepsies and status epilepticus

ABSTRACT

Introduction: Antiseizure drugs (ASDs) play a central and crucial role in the treatment of epilepsy patients, as the majority require anticonvulsant treatment for an extended period of time. Since up to 30% of patients are refractory to medical treatment, new therapeutic options are necessary. Perampanel (PER) and brivaracetam (BRV) are the latest approved ASDs that may be considered in a variety of epilepsy syndromes. PER has a distinct and selective mode of action on α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and is licensed for use in focal and generalized epilepsies. BRV is a derivative of levetiracetam but exhibits a 20-fold higher affinity and a faster brain entry time as a synaptic vesicle glycoprotein 2A (SV2A) ligand.

Areas covered: This article reviews the advances in the epileptic treatment and provides a comparison of PER and BRV. Both drugs have shown comparable results in randomized controlled trials, and both are well tolerated.

Expert opinion: PER and BRV have the potential to perform as important, broad-spectrum ASDs with significant market shares. BRV’s intravenous formulation and fast penetration into the brain and PER’s unique mode of action will result in the more frequent use of both drugs in status epilepticus.

KEYWORDS:

• Seizure
• antiepileptic drugs
• anticonvulsants
• SV2A
• AMPA

Article highlights

• Up to 30% of patients are refractory to medical treatment for epilepsy meaning new therapeutic options are necessary.

• As second available SV2A receptor antagonist, brivaracetam is a well-tolerated, safe and efficient alternative to levetiracetam, especially in patients with behavioral side effects.

• As AMPA receptor antagonist, perampanel is an efficient, safe and well-tolerated antiseizure drug with a unique mode of action.

• Based on their individual mode of action, use of brivaracetam and perampanel in daily practice will increase.

• Brivaracetam and perampanel may be considered in refractory and super-refractory status epilepticus.

This box summarizes key points contained in the article.

Declaration of interest

F Rosenow reports personal fees from Eisai, grants and personal fees from UCB Pharma, grants and personal fees from Desitin Arzneimittel, personal fees from Novartis, personal fees from Medtronic, personal fees from Cerbomed, personal fees from ViroPharma, Sandoz, BayerVital and Shire, grants from the European Union, and grants from Deutsche Forschungsgemeinschaft. A Strzelczyk reports personal fees and grants from Desitin Arzneimittel, Eisai, GW Pharma, LivaNova, Medtronic, Sage Therapeutics, UCB Pharma and Zogenix. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

One referee declares that they have received speaker fees and consultancy fees from UCB and Eisai. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Additional information

Funding

The authors are supported via the Center for Personalized and Translational Epilepsy Research with a LOEWE grant from the State of Hessen.