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

Epilepsy Behav. 2007 May;10(3):449-55. doi: 10.1016/j.yebeh.2007.01.014. Epub 2007 Mar 9.


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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Anticonvulsants / adverse effects
  • Anticonvulsants / therapeutic use*
  • Case-Control Studies
  • Double-Blind Method
  • Epilepsy / complications
  • Epilepsy / drug therapy
  • Female
  • Humans
  • Irritable Mood / drug effects*
  • MMPI / statistics & numerical data
  • Male
  • Middle Aged
  • Mood Disorders / drug therapy*
  • Mood Disorders / etiology
  • Psychoses, Substance-Induced / drug therapy*
  • Psychoses, Substance-Induced / etiology
  • Substance Withdrawal Syndrome / drug therapy*
  • Substance Withdrawal Syndrome / etiology


  • Anticonvulsants