Slight improvement in mood and irritability after antiepileptic drug withdrawal: A controlled study in patients on monotherapy

Objective. Most antiepileptic drugs (AEDs) are considered to have effects on mood and to be effective in a number of affective disorders. 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, double-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. (C) 2007 Elsevier Inc. All rights reserved.