Published online Jan 19, 2026. doi: 10.5498/wjp.v16.i1.112139
Revised: September 15, 2025
Accepted: October 28, 2025
Published online: January 19, 2026
Processing time: 137 Days and 21.9 Hours
Post-stroke depression (PSD) is associated with hypothalamic-pituitary-adrenal (HPA) axis dysfunction and neurotransmitter deficits. Selective serotonin reuptake inhibitors (SSRIs) are commonly used, but their efficacy is limited. This study investigated whether combining SSRIs with traditional Chinese medicine (TCM) Free San could enhance their therapeutic effects.
To evaluate the clinical efficacy and safety of combining SSRIs with Free San in treating PSD, and to assess its impact on HPA axis function.
Ninety-two patients with PSD were enrolled and randomly divided into control groups (n = 46) and study groups (n = 46). The control group received the SSRI paroxetine alone, whereas the study group received paroxetine combined with Free San for 4 weeks. Hamilton Depression Scale and TCM syndrome scores were assessed before and after treatment. Serum serotonin, norepinephrine, cortisol, cor
After treatment, the Hamilton Depression Scale and TCM syndrome scores were significantly lower in the study group than in the control group (P < 0.05). Serum serotonin and norepinephrine levels were significantly higher in the study group than in the control group, whereas cortisol, corticotropin-releasing hormone, and adrenocorticotropic hormone levels were significantly lower (P < 0.05). The total efficacy rates were 84.78% and 65.22% in the study and control groups, respectively (P < 0.05). No significant differences in adverse reactions were observed between the two groups (P > 0.05).
Combining SSRIs with Free San can enhance therapeutic efficacy, improve depressive symptoms, and regulate HPA axis function in patients with PSD with good safety and clinical application value.
Core Tip: Combining selective serotonin reuptake inhibitors with the traditional Chinese medicine Free San significantly improves the treatment efficacy for post-stroke depression. The novel combination therapy not only alleviated depressive symptoms more effectively than selective serotonin reuptake inhibitors alone but also normalized hypothalamic-pituitary-adrenal axis dysfunction, as evidenced by reduced cortisol and corticotropin-releasing hormone levels. This approach has a good safety profile, suggesting that it is a promising integrative treatment strategy for post-stroke depression.