SYSTEMATIC REVIEW article
Front. Pharmacol.
Sec. Ethnopharmacology
This article is part of the Research TopicMedicinal Plants and Brain Health: From Extracts to FormulationsView all 8 articles
Effects of Soyo-san (Xiao-yao-san, Shoyo-san) Combined with Antidepressants on Post-Stroke Depression and Functional Recovery: A Systematic Review and Meta-Analysis
Provisionally accepted
- Wonkwang University, Iksan, Republic of Korea
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Background: Over one-third of stroke survivors experience Post Stroke Depression. Conventional antidepressants are effective but have adverse effects. Soyo-san is an herbal medicine used to treat neuropsychiatric diseases that may exert antidepressant effects with fewer adverse effects. However, there is insufficient evidence synthesizing existing Randomized Controlled Trials to provide comprehensive guidance on the effectiveness and safety of combination treatment with Soyo-san. Purpose: We evaluated the additional benefits and safety of combining Soyo-san with conventional antidepressants for treating Post Stroke Depression through a systematic review and meta-analysis. Methods: A comprehensive search of seven databases was conducted on October 10, 2024, followed by study selection and data extraction. Methodological quality was assessed using the Cochrane Collaboration's risk-of-bias tool, and evidence quality was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation method. Quantitative data synthesis and meta-analysis were conducted using RStudio, along with subgroup, sensitivity, and publication bias analyses. Results: The search retrieved 41 RCTs with 3,628 participants. Soyo-san had a significant effect on depression based on Hamilton Depression Scale score (MD: −4.01; 95% CI: −4.72, −3.30; I²=94%) and total effective rate (RR: 1.21; 95% CI: 1.17, 1.25; I²=0%) with any antidepressant. Moreover, Soyo-san improved post-stroke recovery of motor, cognitive, and sleep dysfunctions. Adverse events were reported in both treatment and control groups in most studies but were less frequent in the former. Conclusions: Modified Soyo-san combined with antidepressants was associated with improvements in depressive symptoms and variety of functional outcomes, though the certainty of evidence is low to very low. Therefore, these findings should be interpreted with caution, and high-quality international trials are needed before firm conclusions can be drawn.
Keywords: Stroke, Post-stroke depression (PSD), Herbal medicine (HM), Systematic review, Soyo-san
Received: 22 Jun 2025; Accepted: 30 Nov 2025.
Copyright: © 2025 Bak, Jin, Yun and Leem. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jong-Min Yun
Jungtae Leem
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