Objective: To explore the effectiveness of duloxetine combined with cognitive behavioral therapy in the treatment of patients with postpartum depression. Methods: A total of 64 patients with postpartum depression who visited our hospital from July 2024 to July 2025 were included as study subjects. The observation group and the control group were divided using a random number table method, with 32 patients in each group. Relevant treatment indicators were compared between the two groups. Results: The total effective rate in the observation group was higher than that in the control group (P < 0.05). After treatment, there were significant differences in HAMD scores, PSQI scores, DAS scores, and serum inflammatory cytokine levels between the observation group and the control group (P < 0.05). However, there was no significant difference in the total incidence of adverse reactions between the two groups (P > 0.05). Conclusion: The combination of duloxetine and cognitive behavioral therapy is effective in the clinical treatment of patients with postpartum depression. It is beneficial for improving sleep quality, depressive symptoms, and dysfunctional cognition, and significantly regulates inflammatory cytokine levels with higher safety. This treatment approach can be widely promoted.
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