New developments in the management of partial-onset epilepsy: role of brivaracetam

Currently, a number of novel anticonvulsant drugs, the so-called third generation, are in various stages of development. Several of them are already available or in ongoing clinical trials. These new compounds should take advantage of new insights into the basic pathophysiology of epileptogenesis, drug metabolism and drug interactions. Many of them still need to be further evaluated mainly in real-world observational trials and registries. Among newer anticonvulsant drugs for partial-onset seizures (POSs), rufinamide, lacosamide, eslicarbazepine and perampanel are those new treatment options for which more substantial clinical evidence is currently available, both in adults and, to some extent, in children. Among the newest anticonvulsant drugs, brivaracetam, a high-affinity synaptic vesicle protein 2A ligand, reported to be 10- to 30-fold more potent than levetiracetam, is highly effective in a broad range of experimental models of focal and generalized seizures. Unlike levetiracetam, brivaracetam does not inhibit high-voltage Ca²⁺ channels and AMPA receptors and appears to inhibit neuronal voltage-gated sodium channels playing a role as a partial antagonist. Brivaracetam has a linear pharmacokinetic profile, is extensively metabolized and is excreted by urine (only 8%-11% unchanged). It does not seem to influence the pharmacokinetics of other antiepileptic drugs. It was approved in the European Union in January 2016 and in the US in February 2016 as an adjunctive therapy for the treatment of POS in patients older than 16 years of age. To date, its clinical efficacy as adjunctive antiepileptic treatment in adults with refractory POS at doses between 50 and 200 mg daily has been extensively assessed in two Phase IIb and four Phase III randomized controlled studies. Long-term extension studies show sustained efficacy of brivaracetam. Overall, the drug is generally well tolerated with only mild-to-moderate side effects. This is true also by intravenous route. Brivaracetam has not yet been evaluated as monotherapy or in comparison with other new anticonvulsant drugs.