Effectiveness and safety of Chaihu-Shugan-San for treating depression based on clinical cases: An updated systematic review and meta-analysis

Zhang X, Zhao Q, Wang Y, Mao Y, Sun Y, Bian X · Medicine · 2024 June 28

Objective

To investigate the efficacy and safety of Chaihu-Shugan-San (CSS) in treating depression by conducting a meta-analysis of clinical studies.

Conclusions

CSS combined with antidepressants was found to be more effective and safer for treating depressed patients compared to traditional antidepressants. Mendelian randomization suggested a causal relationship between amitriptyline and body mass index.

Critical Appraisal

Does adding Chaihu-Shugan-San to antidepressants improve depression more than antidepressants alone?

The review suggests a possible short-term benefit, but does not establish a dependable treatment effect. Across ten trials involving 641 participants, the authors report depression scores averaging 4.2 points lower with the combination on the Hamilton Depression Rating Scale (95% confidence interval: 2.8–5.6 points lower). However, results differed markedly between trials, and the review detected publication bias, meaning favourable findings may be overrepresented. Limited reporting of blinding also leaves uncertainty about whether treatment expectations influenced assessments. The pooled result therefore warrants investigation, but its size and clinical importance should not be assumed to apply consistently across patients, herbal preparations or antidepressants.

Does the review show that Chaihu-Shugan-San can replace antidepressant medication?

No. The authors report no statistically significant difference between the herbal formula alone and antidepressants, but that does not demonstrate equivalent effectiveness. The five contributing trials were small, and the review does not report an equivalence or non-inferiority framework designed to establish an acceptable difference between treatments. Moreover, the printed confidence interval for the depression-score comparison is inconsistent with both the effect estimate and the reported statistical conclusion, preventing reliable interpretation of its precision without corrected data. Treatment periods across the review lasted only two to twelve weeks, leaving sustained recovery and relapse prevention unestablished.

How convincing is the claim that Chaihu-Shugan-San makes depression treatment safer?

The safety findings are preliminary, not proof that the formula alone or in combination is safer. Five add-on trials reported lower adverse-effect symptom scores, but their results varied substantially; the formula-alone safety comparison relied on just one trial of 80 participants. These short-term symptom scores cannot establish the frequency of uncommon serious harms, longer-term toxicity or herb–drug interactions. The separate genetic analysis concerned amitriptyline and body mass index, not Chaihu-Shugan-San, and contains conflicting numerical results across the text, table and figure. It therefore cannot substantiate the review’s comparative safety claim or its suggestion that antidepressants alter patients’ genes.

Assessed 20 Sept 2026.

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Insights

Combining the Traditional Chinese Medicine formula Chaihu-Shugan-San (CSS) with antidepressants results in more effective and safer treatment of depression patients.

The team accessed multiple databases such as PubMed, Embase, Web of Science, SinoMed, China National Knowledge Infrastructure, Chongqing VIP, and Wanfang to gather clinical data. The quality of these studies was gauged using the Cochrane Risk of Bias Tool, after which the data underwent a meta-analysis using Review Manager and Stata software. Information was also extracted from a genome-wide association study, and Mendelian randomization was carried out using R Software. Their analysis incorporated 15 studies involving 1034 patients and six types of antidepressant drugs. It was discovered that a combination of CSS and antidepressants notably improved depressive symptoms, heightened the rate of efficacy, and diminished side effects compared to use of an antidepressant alone. CSS alone also showed fewer side effects compared to a single antidepressant, and, mimicked the depressive symptom improvement provided by antidepressants. The study also used Mendelian randomization to assess the safety of traditional antidepressants, finding a causal relationship between the antidepressant amitriptyline and body mass index.