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This study retrospectively investigated the effectiveness of paroxetine for the treatment of poststroke depression (PSD).Seventy patient cases with PSD were included in this study, and were assigned to an intervention group and a control group equally. All patients received routine treatment in both groups. Additionally, patients in the intervention group underwent paroxetine, while patients in the control group received psychotherapy for a total of 8 weeks intervention. The primary outcomes included depression, measured by Hamilton depression rating scale (HAMD); and anxiety, measured by Hamilton Anxiety Rating Scale (HAMA). The secondary outcomes consisted of neurological impairment, measured by Scandinavian Stroke Scale (SSS), and activities of daily living, measured by Barthel index (BI), as well as the adverse events. All outcomes were assessed before and after 8-week treatment.After 8-week treatments, patients in the intervention group did not show greater effectiveness in depression, measured by HAMD (P = .11), and anxiety, assessed by HAMA (P = .13), as well as the neurological impairment, evaluated by SSS (P = .24), and activities of daily, performed by BI (P = .19), compared with patients in the control group. In addition, no significant differences regarding adverse events were found between the 2 groups.The results of this study indicated that paroxetine may not bring promising effectiveness for patients with PSD. Future studies are still needed to warrant the results of this study.