Differential effects of cognitive behavioral therapy and pharmacotherapy on cognitive function in patients with major depressive disorder: A propensity-weighted longitudinal study

Background Neurocognitive dysfunction is a core feature of major depressive disorder (MDD), predicting relapse, persisting after remission, and hindering functional recovery. Although cognitive behavioral therapy (CBT) and pharmacotherapy are both established treatments, their differential effects on specific neurocognitive domains remain poorly characterized. We investigated the distinct neurocognitive effects of CBT and pharmacotherapy in patients with MDD. Methods This study assessed 69 patients with MDD treated with either manual-based CBT combined with pharmacotherapy (n = 41) or pharmacotherapy alone ( n = 28). Neurocognitive function was evaluated using the Brief Assessment of Cognition in Schizophrenia, whereas depressive and anxiety symptoms were assessed using the Montgomery–Åsberg Depression Rating Scale and Generalized Anxiety Disorder-7, respectively. Inverse probability of treatment weighting (IPTW) based on propensity scores balanced baseline characteristics between groups. Pre–post changes in neurocognitive domains were assessed using repeated-measures ANOVA. Robustness of the findings was evaluated using multiple imputation and mixed-effects models for repeated measures (MMRM). Results After IPTW adjustment, baseline characteristics were well balanced. A significant group × time interaction favoring CBT emerged for verbal memory ( F [1,95] = 4.59, p = .035, η ² = 0.046). Improvements in executive function were observed only in the CBT group ( p = .005, Cohen's d = 0.442). Findings were consistent with the results using multiple imputation and MMRM. Conclusion CBT combined with pharmacotherapy was associated with improvement in verbal memory compared to pharmacotherapy alone. These findings highlight the domain-specific neurocognitive benefits of combining CBT with pharmacotherapy and its potential to target neurocognitive dysfunction in MDD.