The Use of Sertraline in Patients with Epilepsy: Is It Safe? Andres M. Kanner, M.D., 1 Agnes M. Kozak, and Marlis Frey, M.S.N., R.N., CGNP Division of Epilepsy and Clinical Neurophysiology, Department of Neurological Sciences, Rush Medical College, Chicago, Illinois; and Rush Epilepsy Center, Rush–Presbyterian Saint Luke’s Medical Center, Chicago, Illinois 60612 Received January 14, 2000; revised March 17, 2000; accepted for publication March 20, 2000 Purpose. The purpose of this study was to assess the impact of the selective serotonin-reuptake inhibitor (SSRI) sertraline (SRT) on the severity and frequency of seizures of patients with epilepsy. Methods. We prospectively assessed the seizure frequency of 100 consecutive patients with partial (n  95) and primary (n  5) generalized epilepsy during a trial with SRT for the treatment of a depressive (n  97) or obsessive–compulsive (n  3) disorder. We compared the monthly seizure frequency recorded while on SRT with those logged during the 3 and 12 months preceding the start of SRT. A definite causality between seizure worsening and SRT was considered in the following circumstances: (1) occurrence of de novo generalized tonic–clonic seizure (GTC); (2) recurrence of a GTC following a period of at least 1 year without this seizure type; and (3) an increase in the monthly seizure frequency beyond the maximal recorded monthly frequency during both 3- and 12-month periods preceding SRT. A probable causality between SRT and seizure worsening was considered in the case of an increase in monthly seizures beyond the maximal frequency recorded during the 3-month, but not the 12-month, period preceding SRT. Results. Six patients (6%) experienced an increase in seizure frequency after starting SRT. One and five patients met criteria for definite and probable causality between SRT and seizure worsening, respectively. Adjustment of antiepileptic drug doses resulted in a return to baseline seizure frequency in the latter five patients; four patients were kept on SRT at the same doses. The SRT dose of these six patients was significantly lower (57.1  23.8 mg/day vs 111.8  56.8 mg/day; F  6.35, P  0.01) than that of the other 94 patients. Conclusion. SRT can be safely used in the vast majority of patients with epilepsy. © 2000 Academic Press Key Words: sertraline; selective serotonin-reuptake inhibitors; epilepsy; depression; dysthymic disorder. INTRODUCTION Depressive disorders represent the most frequent psychiatric complication of patients with epilepsy (1). In fact, the incidence of depression and suicide has been found to be higher among these patients than in the general population (2). While there is a wide body of research on the risk factors and clinical characteris- tics of depression in epilepsy, the efficacy of antide- pressant drugs (ADs) has yet to be tested in controlled studies in these patients. For example, there has only been one double-blind, placebo-controlled study pub- lished to date on the efficacy of ADs in patients with epilepsy and a major depressive disorder (MDD) (3). In short, depression remains an undertreated compli- cation of epilepsy (4). This phenomenon probably re- flects the temerity of many clinicians of using psych- otropic drugs in these patients because of their poten- tial to cause seizures. Indeed, all non-monoamine 1 To whom all correspondence should be addressed at Depart- ment of Neurological Sciences, Rush–Presbyterian Saint Luke’s Medical Center, 1653 West Congress Parkway, Chicago, IL 60612. Fax: (312) 942-2238. E-mail: akanner@rush.edu. Epilepsy & Behavior 1, 100–105 (2000) doi:10.1006/ebeh.2000.0050, available online at http://www.idealibrary.com on 1525-5050/00 $35.00 Copyright © 2000 by Academic Press All rights of reproduction in any form reserved. 100