Antiepileptic drug pharmacogenetics.

Abstract

Until recently, the drug treatment of epilepsy has been empirical. However, in recent years as a result of improved understanding of seizure neurochemistry and mechanisms of action of antiepileptic drugs (AEDs), drug treatment has become somewhat more rational. Nevertheless, it is currently impossible to predict which patient will respond to a particular AED, and which patient will experience adverse drug effects. The only practical way to determine whether a patient will find a drug useful is to try it. The discovery of genetic polymorphism in drug metabolism has contributed significantly to understanding of the variability in dose-concentration relationships, susceptibility to adverse effects, and susceptibility to seizure intractability. The discovery that predisposition to seizure intractability and expression of brain neuromolecules consequent to seizures is under genetic control may allow a more rational approach to AED choice. In the future, treatment may be guided by a series of pharmacogenetic tests, which would serve not only to choose the most appropriate AED (in terms of efficacy and adverse effects) but also to monitor the antiepileptogenic and the evolution status of the disease.