Nicardipine improves the antidepressant action of ECT but does not improve cognition

Introduction: Cognitive impairment, the most important adverse effect of electroconvulsive therapy (ECT), may involve elevated intracellular calcium ion signaling. Animal research suggests that calcium channel-blocking agents, which attenuate excessive intracellular calcium activity, may reduce cognitive dysfunction caused by ECT. Method: The lipid-soluble calcium channel-blocking drug nicardipine or matching placebo were randomly assigned to 26 patients with major depressive disorder receiving ECT. A rater blind to the experimental condition administered the Hamilton Depression Rating Scale, the Montgomery-Asberg Depression Rating Scale, the Beck Depression Inventory, the Mini-Mental State Examination and a comprehensive battery of neuropsychological tests prior to ECT, at the completion of ECT, and 6 months after ECT completion. Results: Compared with patients receiving placebo, patients taking nicardipine had significantly lower scores on the Hamilton and Montgomery-Asberg but not the Beck Depression rating scale scores at the completion of ECT. There were no differences between placebo and nicardipine groups in depression scores 6 months after ECT. Cognitive function declined over the course of ECT and improved over the next 6 months in both groups, but changes were statistically significant for only two subtests on the neuropsychological battery. Changes in Mini-Mental State Examination scores were small and were not significant at any point. There were no significant differences between nicardipine and placebo treated groups in any assessment of cognition. Discussion: Standard approaches to ECT in younger patients without preexisting neurological impairment do not produce cognitive side effects of sufficient severity for calcium channel-blocking agents to reduce these side effects demonstrably. Studies of treatments for cognitive impairment should be conducted in patients with risk factors for more severe cognitive impairment such as geriatric patients or patients with a history of interictal delirium during previous treatment with ECT. A possible effect of nicardipine in enhancing the antidepressant action of ECT requires further investigation in a study designed to test this action.