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Epilepsy Pharmacologic Decision-making in the Treatment of Focal Epilepsy— A Critical Comparison of Antiepileptic Drugs Selim R Benbadis, MD, 1 Hermann Stefan, MD, 2 Diego A Morita, MD, 3 Bassel Abou-Khalil, MD 4 and R Edward Hogan, MD 5 1. Professor of Neurology, Director, Comprehensive Epilepsy Program, University of South Florida, and Tampa General Hospital, Tampa, Florida, US; 2. Professor, Department of Neurology, University Hospital Erlangen (FAU), Erlangen, Germany; 3. Medical Director, New Onset Seizure Program and Assistant Professor of Pediatrics and Neurology, Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine Cincinnati, Ohio, US; 4. Chief, Division of Epilepsy, Professor of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee, US; 5. Director of the Adult Epilepsy Center and Professor of Neurology, Washington University in St Louis, St Louis, Missouri, US Abstract Physicians who treat patients with epilepsy must balance many factors when selecting the appropriate treatment for an individual patient, including seizure type, concomitant antiepileptic drug (AED) therapy, age, comorbid conditions, and even insurance coverage. Optimal management of seizures is further complicated by a continuously increasing pool of AEDs. As seizure type is a main factor in AED selection, this review will provide an evidence-based guide for physicians treating focal epilepsy. This includes a summary of efficacy, safety, and tolerability data from randomized clinical trials as well as findings related to rational polypharmacy, drug–drug interactions, comorbidities, drug administration (titration, dosing, formulation), US Food and Drug Administration (FDA)-approved indications, and cost. Following the review are four case reports that provide real-life examples of clinical challenges physicians face, particularly when dealing with special populations, which highlight the decision-making process entailed when determining the best course of treatment for patients with epilepsy. Keywords Epilepsy, antiepileptic drug, focal seizures, treatment decisions, enzyme inducers, effectiveness, cost Disclosure: Selim R Benbadis, MD, has served as a consultant for Cyberonics, Eisai, Lundbeck, Sunovion, Supernus, UCB Pharma; is on the speakers bureau for Cyberonics, GlaxoSmithKline, Lundbeck, Supernus, and UCB Pharma; has received grant support from Cyberonics, Lundbeck, Sepracor, Sunovion, Supernus, UCB Pharma, and Upsher-Smith Laboratories; has received royalties as an author or editor for Emedicine-Medscape-WebMD, UpToDate; and is on the Editorial Board for Emedicine-Medscape-WebMD, European Neurology, Epileptic Disorders, Epilepsy and Behavior, and the Expert Review of Neurotherapeutics. Hermann Stefan, MD, has received grant support from Deutsche Forschungsgemeinschaft (DFG-STE 380/14-1, 15-1); has received honoraria from Cyberonics, Desitin, Eisai, Electa, Merz, Novartis, and UCB; has received royalties as an editor of Epilepsy Part I: Basic Principles and Diagnosis: Handbook of Clinical Neurology, and Epilepsy Part II:Treatment: Handbook of Clinical Neurology (Newnes Elsevier 2012); and has served on speakers bureaus for Cyberonics, Desitin, Eisai, Electa, Novartis, and UCB. Diego Morita, MD, serves on the Board of Directors of the Epilepsy Foundation of Greater Cincinnati and Columbus; has served as consultant for Upsher-Smith Laboratories; has received institutional grant support from Eisai; and has received payment for development of educational presentations as CME Course Director, PeerView Press. Bassel Abou- Khalil, MD, has received institutional grant support from GlaxoSmithKline, Pfizer, UCB, Upsher-Smith Laboratories, and Valeant; and has received royalties as an author of the Atlas of EEG & Seizure Semiology (Elsevier 2005). R Edward Hogan, MD, has received institutional funding of clinical trials from Eisai and Upsher-Smith Laboratories; and has served as consultant for Upsher-Smith Laboratories. Acknowledgment: Writing and editorial support was provided by Kristen A Andersen, PhD, of Prescott Medical Communications Group in Chicago, Illinois and was funded by Upsher-Smith Laboratories, Inc., Maple Grove, Minnesota, US. Received: July 16, 2014 Accepted: August 7, 2014 Citation: US Neurology, 2014;10(2):92–103 Correspondence: Selim R Benbadis, MD, Director, University of South Florida/Tampa General Hospital Comprehensive Epilepsy Program, 2 Tampa General Circle, 6th Floor, Tampa, Florida, US. E: Support: The publication of this article was supported by Upsher-Smith Laboratories, Inc. The views and opinions expressed are those of the authors and not necessarily those of Upsher-Smith Laboratories, Inc. Epilepsy is a general term used to describe a collection of common, chronic conditions of recurrent and unpredictable seizures. While seizures in newly diagnosed patients are often controlled with a single antiepileptic drug (AED), 1 the estimated 30–40 % of patients who are resistant to monotherapy could benefit from a combination of two or more carefully selected AEDs. 2,3 92 The reasons for AED treatment failures are as complex as the disease itself and likely depend, at least partly, on initial treatment decisions. 4 Prior to the recent influx of nearly two dozen AEDs to the pharmacopeia, treatment choices in epilepsy were fairly straightforward, but arguably © TOU C H ME D ICA L ME D IA 2014