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This retrospective study investigated the efficacy and safety of escitalopram oxalate (ESO) for the treatment of post-stroke depression (PSD).A total of 115 patients with PSD were included in this study. A total of 65 patients underwent ESO (Intervention group). A total of 50 patients received acupressure (Control group). The outcome measurements included Montgomery-Åsberg Depression Rating Scale (MADRS), Hamilton Anxiety Rating Scale (HAM-A), and Sheehan Disability Scale (SDS). In addition, we also recorded the adverse events in this study.At the end of 8-week treatment, ESO showed greater efficacy in depression, measured by MADRS (P < .01); anxiety, measured by HAM-A scale (P < .01); and disability, measured by SDS (P < .01), compared to acupressure. Additionally, there were not significant differences regarding adverse events between two groups (P > .05).The present results indicate that ESO can decrease symptoms of patients with PSD.