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Keywords:

  • Epilepsy;
  • Refractory;
  • Intractable;
  • Treatment-resistant;
  • Nonresponders;
  • Responder;
  • Pharmacoresistance;
  • Pharmacogenomics;
  • Prognostic factors

Summary:  The incidence of refractory epilepsy remains high despite the influx of many new antiepileptic drugs (AEDs) over the past 10 years. Epidemiological data indicate that 20–40% of the patients with newly diagnosed epilepsy will become refractory to treatment. Factors that may be used to predict whether or not a patient will respond favorably to AED therapy include the type of epilepsy, underlying syndrome, etiology, and the patient's history of seizure frequency, density, and clustering. Environmental factors, such as trauma and prior drug exposure, and genetic factors that predetermine the rate of absorption, metabolism, and uptake of a drug by target tissue may also uniquely impact an individual and influence their response to AED therapy. Treatment resistance is, therefore, a multifaceted phenomenon. Since individuals with refractory epilepsy do not share a common reason for their treatment resistance, the use of targeted drug therapies may be our best option for improving treatment outcomes in this patient population. Pharmacogeneticists are currently attempting to understand the genetic basis of refractory epilepsy so that they can identify subgroups of patients who share a common genetic background and then target drug therapies to meet their specific needs.