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  • Clinical Implications
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Clinical Implication

Defining the clinical role of pharmacogenetics in antiepileptic drug therapy

The Pharmacogenomics Journal volume 6, pages 357–359 (2006)Cite this article

Evidence continues to accumulate suggesting that genetic variation is at least partly responsible for interindividual differences in clinical response to essentially all classes of drugs, including those used to treat patients with epilepsy. Despite the recent emphasis placed upon the concept of pharmacogenetics, it has been difficult to assess accurately the relative importance of gene variation in antiepileptic drug (AED) therapy. To date, the main focus of AED pharmacogenetic research has been older drugs of established clinical value, particularly, phenytoin (PHT) and carbamazepine (CBZ). Other standard agents such as valproic acid (VPA), ethosuximide (ETX), barbiturates and benzodiazepines have not been systematically studied, nor have newer drugs such as gabapentin, lamotrigine (LTG), felbamate, tiagabine, topiramate (TPM), vigabatrin (VGB), oxcarbazepine (OXC), levetiracetam and zonisamide. This limitation in fundamental data prohibits broad application of genetic information in the clinical use of AEDs at the present time.

In determining pharmacological treatment for any new epilepsy patient, a clinician must address two basic questions: ‘Which drug?’ and ‘Which dose?’. Ideally, the answers to these questions lead to an efficacious and well-tolerated AED treatment. Based on clinical trial data, mechanisms of action, and clinical experience, certain AEDs are generally preferred for focal epilepsy (CBZ, OXC, PHT) and other AEDs are preferred for generalized epilepsy (VPA, ETX, LTG, TPM).1, 2 With rare exceptions, such as VGB as the preferred AED for infantile spasms due to tuberous sclerosis,3 etiology of epilepsy plays little or no role in AED selection. Similarly, since studies have not yet begun to address genetic determinants of drug efficacy, pharmacogenetics also currently plays no role. There is thus a critical need for prospective studies involving a wider variety of common AEDs in order to begin to develop more rational therapeutic strategies.

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Authors and Affiliations

  1. Divison of Neurology, The Children's Hospital of Philadelphia, Philadelphia, PA, USA

    D J Dlugos

  2. Department of Neurology, University of Cincinnati, Cincinnati, OH, USA

    R J Buono

  3. Departments of Psychiatry and Pharmacology, University of Pennsylvania, Philadelphia, PA, USA

    T N Ferraro

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  1. D J Dlugos
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  2. R J Buono
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  3. T N Ferraro
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Correspondence to T N Ferraro.

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Duality of interest

TNF was supported by NIH Grant NS39516.

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Dlugos, D., Buono, R. & Ferraro, T. Defining the clinical role of pharmacogenetics in antiepileptic drug therapy. Pharmacogenomics J 6, 357–359 (2006). https://doi.org/10.1038/sj.tpj.6500379

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