Departments of Psychiatry and Pharmacology, University of Pennsylvania, Philadelphia,PA, USAThe Pharmacogenomics Journal (2006) 6,357–359. doi:10.1038/sj.tpj.6500379;published online 28 February 2006Evidence continues to accumulate sug-gesting that genetic variation is at leastpartly responsible for interindividualdifferences in clinical response to es-sentially all classes of drugs, includingthose used to treat patients with epi-lepsy. Despite the recent emphasisplaced upon the concept of pharmaco-genetics, it has been difficult to assessaccurately the relative importance ofgene variation in antiepileptic drug(AED) therapy. To date, the main focusof AED pharmacogenetic research hasbeen older drugs of established clinicalvalue, particularly, phenytoin (PHT)and carbamazepine (CBZ). Other stan-dard agents such as valproic acid (VPA),ethosuximide (ETX), barbiturates andbenzodiazepines have not been system-atically studied, nor have newerdrugs such as gabapentin, lamotrigine(LTG), felbamate, tiagabine, topiramate(TPM), vigabatrin (VGB), oxcarbaze-pine (OXC), levetiracetam and zonisa-mide. This limitation in fundamentaldata prohibits broad application ofgenetic information in the clinical useof AEDs at the present time.Impact of pharmacogenetics onantiepileptic drug selectionIn determining pharmacological treat-ment for any new epilepsy patient, aclinician must address two basic ques-tions: ‘Which drug?’ and ‘Whichdose?’. Ideally, the answers to thesequestions lead to an efficacious andwell-tolerated AED treatment. Basedon clinical trial data, mechanisms ofaction, and clinical experience, certainAEDs are generally preferred for focalepilepsy (CBZ, OXC, PHT) and otherAEDs are preferred for generalizedepilepsy (VPA, ETX, LTG, TPM).