Pharmacogenetics of AED development

Numerous examples can be found throughout medicine of differences in individual patient responses to medications. These differences can involve efficacy, potency, and adverse reactions. This is also true for drugs used to treat epilepsy, and recent work in pharmacogenetics has begun to unravel the myriad contributing factors to individual responses to antiepileptic drug (AED) therapy. A number of genetic variations are now known to influence both the pharmacokinetics and pharmacodynamics of AEDs. In addition, changes in the regulation of neuronal and glial gene expression following seizure activity can also influence the response to drugs. Finally, the problem of refractory, or pharmacoresistant, epilepsy may very well also have its roots in pharmacogenetics. In this chapter, we highlight some of the most recent findings in patients and animal models that are relevant to individual variations in response to antiepileptic drugs, how these findings might ultimately impact AED development and personalized therapy, and what challenges remain for the effective use of pharmacogenetic information in the development of treatments for epilepsy.