Patient-tailored antiepileptic drug therapy: Predicting response to antiepileptic drugs.

Antiepileptic drugs (AEDs) are characterized by a narrow therapeutic index, requiring tailoring of therapy to the individual patient. When choosing an AED, the most important predictors of therapeutic response are seizure type and epilepsy syndrome. Some AEDs have a broad spectrum of efficacy against all seizures while others have a narrow spectrum and may even aggravate certain seizure types. Preliminary data suggest that expression of multiple drug resistance genes may be a cause of intractability to certain AEDs.Because AEDs differ in their side effect profiles, tolerability is a major factor in drug selection. Hypersensivity reactions to certain AEDs are related to genetic defects in drug metabolism, and may be predicted by in vitro tests. Many other predictors of susceptibility to specific adverse drug reactions have been identified empirically.AEDs exhibit a large pharmacokinetic variability, and individualizing dosage is as essential as choosing the correct drug. Pharmacokinetic variability is related primarily to differences in rate of drug metabolism due to genetic and developmental factors, drug interactions and associated disease. Methylphenobarbital, mephenytoin and, to a lesser extent, phenytoin and phenobarbital are substrates for the genetically polymorphic enzyme CYP2C19. Mutations in genes encoding for CYP2C19 and/or CYP2C9 may predict reduced dosage requirements for these drugs. Measurement of serum drug levels can be of value in individualizing AED dosage, even though the value of therapeutic drug monitoring for newer generation AEDs remains unclear.