The potential of pharmacogenetics in the treatment of epilepsy

Pharmacogenetics studies how genetic variants influence individual drug responses. Although pharmacogenetics is currently the subject of intensive research in several disease domains, it remains relatively unexplored in the field of epilepsy. Drug treatment of epilepsy is characterized by unpredictability of efficacy, adverse drug reactions and optimal doses in individual patients. Moreover, a substantial fraction of patients develop drug refractory epilepsy despite optimal treatment. Insights in the pathogenesis of epilepsy and the mechanisms of action of antiepileptic drugs (AEDs) have improved our understanding of the genetic determinants of AED response. The first reports in epilepsy pharmacogenetics are becoming available, and large-scale pharmacogenetic studies are now possible thanks to recent advances in genetics and decreasing genotyping costs. It is hoped that ultimately, findings in epilepsy pharmacogenetics will lead to a more efficacious and less harmful treatment of epilepsy, development of more effective AEDs and facilitation of clinical trials of new AEDs. However, although pharmacogenetics will undoubtedly improve our insight into the mechanisms underlying response to AEDs and perhaps into the pathogenesis of drug refractory epilepsy, clinical application of any findings is expected to be a long process, and considerable practical and theoretical hurdles need to be overcome before pharmacogenetic information will prove of any major utility in the clinical setting. This review addresses current knowledge on genetic factors contributing to AED response and discusses the potential of epilepsy pharmacogenetics in the clinical treatment of epilepsy and new AED development. (C) 2006 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.