Assessing the Efficacy of Cognitive Enhancers in Electroconvulsive Therapy: A Randomized Controlled Trial of Rivastigmine and Memantine

Objective: Electroconvulsive therapy (ECT) is an effective treatment for severe psychiatric disorders but is frequently associated with cognitive side effects. This study aimed to evaluate the effects of rivastigmine and memantine on cognitive function following ECT. Methods: In this multicenter, randomized, double-blind, placebo-controlled trial (registration number: IRCT20190119042417N2), 45 patients receiving ECT were allocated equally to rivastigmine, memantine, or placebo groups. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA) at baseline, week 2, and week 6. Individual slopes of MoCA change over time were computed using simple linear regression, and group-level comparisons were conducted using t tests and adjusted linear models. Results: Patients receiving rivastigmine showed a significantly greater improvement in weekly MoCA scores compared with placebo (mean slope=+0.42 vs. –0.11 points/week; P =0.006; Cohen d=1.40). Memantine was associated with a positive slope (+0.24 points/week), but the effect was not statistically significant after adjusting for baseline cognitive status and covariates. Conclusions: Rivastigmine may enhance cognitive recovery following ECT. Memantine showed a positive but nonsignificant effect. These findings support the potential utility of cholinergic modulation in mitigating ECT-related cognitive deficits. Future research should explore combination therapies and utilize more sensitive, domain-specific cognitive assessments.