Drug treatment of
epilepsy is characterized by unpredictability of efficacy,
adverse drug reactions, and optimal doses in individual patients, which, at least in part, is a consequence of genetic variation. Since genetic variability in drug metabolism was reported to affect the treatment with
phenytoin more than 25 years ago, the ultimate goal of pharmacogenetics is to use the genetic makeup of an individual to predict drug response and efficacy, as well as potential
adverse drug events. However, determining the practical relevance of pharmacogenetic variants remains difficult, in part because of problems with study design and replication. This article reviews the published work with particular emphasis on pharmacogenetic alterations that may affect efficacy, tolerability, and safety of
antiepileptic drugs (AEDs), including variation in genes encoding drug target (SCN1A), drug transport (ABCB1), drug metabolizing (
CYP2C9,
CYP2C19), and human leucocyte
antigen (HLA)
proteins. Although the current studies associating particular genes and their variants with seizure control or adverse events have inherent weaknesses and have not provided unifying conclusions, several results, for example that Asian patients with a particular HLA allele,
HLA-B*1502, are at a higher risk for
Stevens-Johnson syndrome when using
carbamazepine, are helpful to increase our knowledge how genetic variation affects the treatment of
epilepsy. Although genetic testing raises ethical and social issues, a better understanding of the genetic influences on
epilepsy outcome is key to developing the much needed new therapeutic strategies for individuals with
epilepsy.