Brivaracetam for the treatment of epilepsy

Epilepsy is one of the most common neurological disorders, affecting about 1% of the population worldwide. With currently available antiepileptic drugs, one-third of patients continue to suffer from seizures even when treated at maximally tolerated dosages, either in monotherapy or in various drug combinations. Pharmacoresistance is associated with physical risks, reduced life expectancy, reduced quality of life and impairments in social opportunities. The acetamide derivate levetiracetam (LEV) that primarily targets the synaptic vesicle protein 2A has been one of the most successful second-generation antiepileptic drugs.

This article reviews a rationally designed LEV derivative, brivaracetam (BRV), which has an increased affinity to the LEV-binding site. BRV has shown some efficacy in the treatment of progressive myoclonus epilepsy and is under development to be used as an add-on treatment of focal epilepsy. Evidence is given for possible advantages related to the higher intrinsic antiepileptic efficacy of BRV and its antiepileptic potential in relation to a wide spectrum of epilepsy forms and for possible disadvantages related to hepatic metabolism and to a lower therapeutic index related to additional intrinsic activity at the sodium channel. An update on pharmacodynamic, pharmacokinetic and study data published until 2010 on BRV is given.

BRV is a rationally developed third-generation antiepileptic drug with higher binding to SV2A and additional mechanisms of actions. Animal studies are promising regarding its efficacy in a wide spectrum of epilepsy models. Clinical studies have shown good tolerability at dosages of up to 50 mg/day but have yet to identify the optimal dose range and to prove an additional value of the drug in terms of seizure control.