Pharmacological treatment of epilepsy in adolescents and adults

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By Patrick Kwan MD and Martin J Brodie MD

The International League Against Epilepsy has recently published the first ever global consensus definition of drug-resistant epilepsy. Ezogabine (retigabine) has been approved by the U.S. Food and Drug Administration (and its European counterpart) for adjunctive treatment of partial seizures with or without secondary generalization in adults. It is the first antiepileptic drug that specifically acts by opening potassium channels. With the seemingly unstoppable development of a range of newer antiepileptic drugs over the past 2 decades, the available choice has been substantially widened, and the number of possible drug combinations for the treatment of epilepsy is almost limitless. Developing a framework to use antiepileptic drugs rationally, therefore, has become an issue not only of academic interest but also of practical necessity. In this clinical article, Dr. Patrick Kwan and Dr. Martin Brodie provide an updated overview of the pharmacotherapy of epilepsy in adolescents and adults, with particular reference to the clinical pharmacology of antiepileptic drugs, approaches to treatment, and principles of drug selection.

Key Points

  • Antiepileptic drug treatment is generally recommended after 2 or more unprovoked seizures.
  • Selection of antiepileptic drugs should be individualized based on the seizure type/epilepsy syndrome, potential adverse effects, and drug to drug interactions.
  • Sixty percent to 70% of newly diagnosed patients will become seizure-free with antiepileptic drug therapy, mostly when taking their first or second drug schedule, and often requiring no more than modest or moderate drug doses.
  • The International League Against Epilepsy (ILAE) defines drug-resistant epilepsy as “failure of adequate trials of 2 tolerated and appropriately chosen and used AED schedules (whether as monotherapies or in combination) to achieve sustained seizure freedom.”
  • Patients with drug-resistant epilepsy should be referred to specialist centers for a comprehensive review of the diagnosis and management, and consideration of other therapeutic options, particularly epilepsy surgery.