Brivaracetam for the treatment of epilepsy.
Summary of "Brivaracetam for the treatment of epilepsy."
Introduction: 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. Areas covered: 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. Expert opinion: 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.
Affiliation
University Hospital Freiburg, Epilepsy Center, Breisacher Str. 64, D-79106 Freiburg , Germany +49 761 2705366 ; +49 761 2705003 ; andreas.schulze-bonhage@uniklinik-freiburg.de.
Journal Details
This article was published in the following journal.
Name: Expert opinion on pharmacotherapy
ISSN: 1744-7666
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21682662
- DOI: http://dx.doi.org/10.1517/14656566.2011.591380
Medical and Biotech [MESH] Definitions
Anterior Temporal Lobectomy
A neurosurgical procedure that removes the anterior TEMPORAL LOBE including the medial temporal structures of CEREBRAL CORTEX; AMYGDALA; HIPPOCAMPUS; and the adjacent PARAHIPPOCAMPAL GYRUS. This procedure is generally used for the treatment of intractable temporal epilepsy (EPILEPSY, TEMPORAL LOBE).
Myoclonic Epilepsy, Juvenile
A disorder characterized by the onset of myoclonus in adolescence, a marked increase in the incidence of absence seizures (see EPILEPSY, ABSENCE), and generalized major motor seizures (see EPILEPSY, TONIC-CLONIC). The myoclonic episodes tend to occur shortly after awakening. Seizures tend to be aggravated by sleep deprivation and alcohol consumption. Hereditary and sporadic forms have been identified. (From Adams et al., Principles of Neurology, 6th ed, p323)
Epilepsy
A disorder characterized by recurrent episodes of paroxysmal brain dysfunction due to a sudden, disorderly, and excessive neuronal discharge. Epilepsy classification systems are generally based upon: (1) clinical features of the seizure episodes (e.g., motor seizure), (2) etiology (e.g., post-traumatic), (3) anatomic site of seizure origin (e.g., frontal lobe seizure), (4) tendency to spread to other structures in the brain, and (5) temporal patterns (e.g., nocturnal epilepsy). (From Adams et al., Principles of Neurology, 6th ed, p313)
Mephenytoin
An anticonvulsant effective in tonic-clonic epilepsy (EPILEPSY, TONIC-CLONIC). It may cause blood dyscrasias.
Epilepsy, Rolandic
An autosomal dominant inherited partial epilepsy syndrome with onset between age 3 and 13 years. Seizures are characterized by PARESTHESIA and tonic or clonic activity of the lower face associated with drooling and dysarthria. In most cases, affected children are neurologically and developmentally normal. (From Epilepsia 1998 39;Suppl 4:S32-S41)
PubMed Articles
Brivaracetam is a novel synaptic vesicle protein 2A (SV2A) ligand reported to be 10 fold more potent than levetiracetam in animal models of epilepsy. This study reports the binding profile of brivarac...
Brivaracetam does not alter spatial learning and memory in both normal and amygdala-kindled rats.
Several antiepileptic drugs (AEDs) may induce memory deficits when tested in preclinical models at doses that exert significant protection against seizures. Brivaracetam (BRV) is a novel high-affinity...
Epilepsy treatment gap: prevalence and associated factors in Southeast Nigeria.
OBJECTIVES: The treatment gap of epilepsy in developing countries is high, and data on the magnitude and causes of epilepsy treatment gap in Africa are sparse. We aimed to determine the prevalence and...
Many people with epilepsy report treatment-emergent adverse effects (AEs) while on drug therapy despite optimized treatment. We explored the level of treatment satisfaction with current management amo...
Children's access to treatment for epilepsy: experience from the Lao People's Democratic Republic.
Epilepsy affects an estimated 10.5 million children worldwide, of whom 80% live in developing countries. The treatment gap is estimated at around 90% in the Lao People's Democratic Republic (Lao PDR)....
Clinical Trials
This will be the first study with brivaracetam in children suffering from epilepsy, preceding further evaluation of its efficacy and tolerability.
New treatments should be made available to epileptic patients. Studies using brivaracetam in adults with epilepsy have shown promising results. This study will confirm the efficacy and saf...
New treatments should be made available to epileptic patients. Studies using brivaracetam in adults with epilepsy have shown promising results. This study will confirm the efficacy and saf...
This trial, evaluating the long-term safety and tolerability of brivaracetam will provide subjects suffering from epilepsy, who may have benefited from brivaracetam as adjunctive treatment...
This trial will evaluate the efficacy and safety of brivaracetam (at doses of 5, 20 and 50mg/day in b.i.d. administration) as add on therapy in subjects with focal epilepsy and help to nar...
