rational polytherapy with antiepileptic drugs理性polytherapy与抗癫痫药物.pdfVIP

Pharmaceuticals 2010, 3, 2362-2379; doi:10.3390/ph3082362 OPEN ACCESS pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Review Rational Polytherapy with Antiepileptic Drugs Jong Woo Lee * and Barbara Dworetzky The Edward B. Bromfield Epilepsy Program, Division of EEG, Epilepsy, and Sleep Neurology, Department of Neurology, Brigham and Women’s Hospital, Boston, MA 02115, USA; E-Mail: bdworetzky@ (B.D.) * Author to whom correspondence should be addressed; E-Mail: jlee38@ ; Tel.: +1 617-732-7547; Fax: +1 617-730-2885. Received: 30 June 2010; in revised form: 21 July 2010 / Accepted: 22 July 2010/ Published: 26 July 2010 Abstract: Approximately 30–40% of patients do not achieve seizure control with a single antiepileptic drug (AED). With the advent of multiple AEDs in the past 15 years, rational polytherapy, the goal of finding combinations of AEDs that have favorable characteristics, has become of greater importance. We review the theoretical considerations based on AED mechanism of action, animal models, human studies in this field, and the challenges in finding such optimal combinations. Several case scenarios are presented, illustrating examples of rational polytherapy. Keywords: antiepileptic drug; rational polytherapy; epilepsy 1. Introduction Until the early 1980’s, polytherapy was widely practiced as first-line treatment for refractory epilepsy with the hope of achieving synergistic effects or less severe drug toxicity on smaller doses of two drugs rather than larger doses of one drug