Differential effects of serotonergic and noradrenergic antidepressants on brain activity during a cognitive control task and neurofunctional prediction of treatment outcome in patients with depression

Background: We investigated the differential effects of serotonergic and noradrenergic antidepressants on brain activation in patients with major depressive disorder during a Stroop task. We predicted that pretreatment hyperactivity in the rostral anterior cingulate cortex would predict better treatment outcomes. Methods: In total, 20 patients underwent naturalistic open-label clinical treatment with citalopram ( n = 12) or reboxetine ( n = 8). We performed functional magnetic resonance imaging at baseline and after 6 weeks of treatment. Results: There were no significant group differences in clinical characteristics, treatment outcomes or baseline fMRI activations. The group by time interaction revealed significant voxels in the right amygdala–hippocampus complex ( p < 0.05, family-wise error corrected by use of the bilateral amygdala and hippocampus mask image as a small volume), indicating a posttreatment blood oxygen level–dependent signal decrease in the citalopram group. Pretreatment hyperactivity in the rostral anterior cingulate cortex was not related to symptom improvement. Limitations: Our study was a nonrandomized clinical trial. Conclusion: These results indicate that serotonergic and noradrenergic antidepressants have a differential effect on brain activity, especially in the amygdala and hippocampus.