Electroconvulsive brain stimulation may represent the strongest manipulation available to study brain plasticity in humans. Brain plasticity induced by electroconvulsive brain stimulation, profoundly improves disturbed emotion and motivation in patients with depression. Electroconvulsive therapy (ECT) is a highly effective and safe treatment for psychiatric disorders like severe depression. However, there is ongoing concern about the negative impact of ECT on brain function and cognition that is, surprisingly, only seen in a part of the treated patients. After 80 years of research on ECT, virtually nothing is known about the mechanisms underlying these strong individual differences in cognitive changes induced by ECT. A first step would be to better quantify the pattern and severity of the adverse cognitive outcomes in order to better distinguish patients that suffer from adverse cognitive outcomes from those that do not or even improve. By better distinguishing of these subgroups, a second step towards understanding can be taken: to identify the factors that predict adverse cognitive outcomes. Our research aims to advance understanding of the mechanisms of cognitive plasticity and reveal the pre-treatment profiles that render a patient cognitive vulnerable or resilient.

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.

The aim of this study was to assess cognitive effects of anticonvulsants in a way that would yield results that are most directly applicable to epilepsy populations. This was done with a placebo-controlled, prospective, randomized, double-blind, parallel group study of anticonvulsant withdrawal in a population of subjects taking a single anticonvulsant with completely controlled seizures. Outcomes of this study on cognitive measures from the California Computerized Assessment Package have recently been reported. To aid comparison with results of prior studies, we report outcomes here on several more standard measures of neuropsychological function. The major findings were that, in subjects with therapeutic drug levels at baseline, drug withdrawal was associated with significant improvement in performance on the Controlled Oral Word Association Test and the Stroop Color–Word Interference Test. Comparable results were achieved in the subgroup taking carbamazepine. (JINS, 2007, 13, 393–400.)