Epilepsia
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Review Comparative Study
Concerns with antiepileptic drug initiation: safety, tolerability, and efficacy.
A number of commonly used antiepileptic drugs (AEDs) produce severe adverse effects if they are introduced at their usual daily maintenance doses. Gradual slow titration of the dose often avoids these adverse effects almost entirely. ⋯ Examples of drugs that require gradual introduction are lamotrigine, carbamazepine, topiramate, tiagabine, and zonisamide. Phenytoin, oxcarbazepine, gabapentin, valproate, and levetiracetam are examples of drugs that can be started at an effective dose.
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Responses among patients to antiepileptic drugs (AEDs) may be highly variable, with respect to both drug efficacy and safety. Pharmacogenetics addresses the genetic component of such patient variability. Differential response to phenytoin, for example, is related to interindividual genetic differences in the metabolic enzyme CYP2C9, and to a lesser extent, CYP2C19. ⋯ Further understanding of the role of genes in AED response will depend on clinical investigations coupled with new information and technologies derived from the Human Genome Project. Once the DNA sequences involved in specific AED responses are understood, they can be used as the basis of clinical assays to predict the most likely response in each individual patient. The combination of clinical investigations, genomics, and emerging testing methodologies should lead to new tools for the effective management of epilepsy.