Slight improvement in mood and irritability after antiepileptic drug withdrawal: A controlled study in patients on monotherapy Erik Hessen a,b, * , Morten I. Lossius a,b,c , Ivar Reinvang d , Leif Gjerstad e a Helse Øst Health Services, Akershus University Hospital, 1478 Lorenskog, Norway b Department of Neurology, Akershus University Hospital, Lorenskog, Norway c National Center for Epilepsy, Rikshospitalet, University of Oslo, Oslo, Norway d Department of Psychology, University of Oslo, Oslo, Norway e Department of Neurology, Rikshospitalet and Faculty of Medicine, University of Oslo, Oslo, Norway Received 19 December 2006; revised 24 January 2007; accepted 26 January 2007 Available online 9 March 2007 Abstract Objective. Most antiepileptic drugs (AEDs) are considered to have effects on mood and to be effective in a number of affective dis- orders. There are, however, conflicting reports in the literature with respect to the psychotropic properties of AEDs. Many of the studies have a number of methodological problems, and much uncertainty still exists regarding the behavioral and mood effects of AEDs. The aim of this study was to assess, in a randomized, double-blind, placebo-controlled study of seizure-free patients with epilepsy, the effect of withdrawal of AEDs in patients on monotherapy on measures of mood and behavior. Methods. One hundred fifteen subjects who had been seizure-free >2 years on drug monotherapy went through a randomized, dou- ble-blind, placebo-controlled study. Each patient was included for 12 months or until seizure relapse. Behavioral function was assessed with the Minnesota Multiphasic Personality Inventory 2 (MMPI-2) at baseline and 7 months after withdrawal. Results. Discontinuation of AEDs resulted, to a greater extent than continued treatment, in a slight improvement in symptoms of depression and irritability. Comparable results were achieved in the subgroup taking carbamazepine. For patients with a high degree of depressive and somatic symptoms at baseline, no significant differences in symptoms emerged in the withdrawal group compared with the non-withdrawal group. Conclusion. The results suggest that seizure-free patients with epilepsy on monotherapy can obtain a slight improvement in symptoms characteristic of depression and irritability if they discontinue treatment with AEDs. The described changes are limited, and the functional impact is of uncertain significance. Ó 2007 Elsevier Inc. All rights reserved. Keywords: Antiepileptic drugs; Behavioral side effects; Mood; Carbamazepine; Drug withdrawal 1. Introduction The behavioral consequences of antiepileptic drugs (AEDs) are an important aspect of the management of people with epilepsy [1]. There are conflicting reports in the literature with respect to the psychotropic properties of AEDs. As with the literature on possible cognitive side effects of AEDs, methodological problems often contribute to the variability in the findings on behavioral effects of AEDs [2–4]. The most common methodological limitations are: different selections of subjects and diverse test proce- dures in different studies, making comparison of the results difficult [5]; frequent lack of control groups and randomi- zation of the treatment; and small numbers of subjects and, therefore, a lack of statistical power. Studies of withdrawal from AEDs in seizure-free patients with epilepsy can be valuable because they may serve as an assessment of the potential behavioral side 1525-5050/$ - see front matter Ó 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.yebeh.2007.01.014 * Corresponding author. Fax: +47 22921783. E-mail address: erik.hessen@nevropsykologi.no (E. Hessen). www.elsevier.com/locate/yebeh Epilepsy & Behavior 10 (2007) 449–455