Background: Patients with major depressive disorder (MDD) have abnormal functional interaction among largescale brain networks, indicated by aberrant effective connectivity of the default mode network (DMN), salience network (SN), and dorsal attention network (DAN). However, it remains unclear whether antidepressants can normalize the altered effective connectivity in MDD. Methods: In this study, we collected resting-state functional magnetic resonance imaging data from 46 unmedicated patients with MDD at baseline and after 12 weeks of escitalopram treatment. We also collected data from 58 healthy controls (HCs) at the same time point with the same interval. Using spectral dynamic causal modeling and parametric empirical Bayes, we examined group differences, time effect and their interaction on the casual interactions among the regions of interest in the three networks. Results: Compared with HCs, patients with MDD showed increased positive (excitatory) connections within the DMN, decreased positive connections within the SN and DAN, decreased absolute value of negative (inhibitory) connectivity from the SN and DAN to the DMN, and decreased positive connections between the DAN and the SN. Furthermore, we found that six connections related to the DAN showed decreased group differences in effective connectivity between MDD and HCs during follow-up compared to the baseline. Conclusions: Our findings suggest that escitalopram therapy can partly improve the disrupted effective connectivity among high-order brain functional networks in MDD. These findings deepened our understanding of the neural basis of antidepressants' effect on brain function in patients with MDD.