Improvement in Speeded Cognitive Processing After Anti-epileptic Drug Withdrawal – A Controlled Study in Mono-therapy Patients

Abstract

Background: Anti-epileptic drugs (AEDs) are associated with cognitive side effects. Doubt exists regarding the degree of cognitive effects primarily related to problems with design and methodology in many studies. The aim of the reported study was to assess the effect of AED withdrawal in patients on monotherapy using computerised measures of attention, reaction time and speed of information processing. Methods: One hundred and fifty patients seizure free >2 years on drug monotherapy went through a randomised, double blind, placebo controlled study. All patients were included for 12 months or until seizure relapse. Cognitive function was assessed with the California Computerized Assessment Package at baseline and 7 months after withdrawal. Results: The major finding was that discontinuation of major AEDs significantly improved performance on tests that require complex cognitive processing under time pressure. The difference in speed of cognitive processing between the withdrawal and non-withdrawal groups was between 24 and 43 ms. No significant difference emerged between the groups on simple tasks of attention and reaction time. Most of the patients in the study were treated with carbamazepine and valproate. The outcome of carbamazepine withdrawal was similar to the outcome for the total study population while discontinuation of valproate only revealed a non-significant tendency in the same direction. Interpretation: The results suggest that seizure-free epilepsy patients on monotherapy can obtain improvement in speeded cognitive processing if they withdraw anti-epileptic treatment.