A Multicenter Real-World Study Evaluating the Efficacy and Safety of Shugan Jieyu Capsules in the Treatment of Depression

Depression is a mood disorder caused by various factors, characterized by prominent and persistent depressive symptomatology and severe impairment of social functioning. The severity of depression is typically classified based on the number and type of symptoms and the degree of functional impairment, and is divided into mild, moderate, and severe. Although symptoms may remit spontaneously in some patients with mild depression, a subset may progress to severe depression within one year; without treatment, this can lead to functional impairment, reduced quality of life, and even chronicity. Current treatment for moderate-to-severe depression remains primarily pharmacological, with selective serotonin reuptake inhibitors (SSRIs) being among the most commonly used antidepressants in clinical practice. Traditional Chinese medicine (TCM) often contains multiple active ingredients. Compared with Western medicines, the advantages of TCM are not only reflected in its efficacy, but also in the protection of patients' overall health and improvement of quality of life.

Existing studies have demonstrated the efficacy advantages of integrated TCM-Western medicine approaches, which can produce synergistic effects, shorten the time to antidepressant onset, improve medication adherence, reduce adverse reactions, enhance quality of life, and improve clinical remission rates and safety. However, most existing studies focus on patients with a specific severity of depression using a fixed combination of a particular TCM and antidepressant. For patients with different severity of depression, how to better leverage the advantages of integrated treatment-especially by adjusting individualized regimens based on patient response during treatment-remains an important yet underexplored area.

Previous clinical studies of Shugan Jieyu Capsules have been predominantly randomized controlled trials (RCTs), conducted in relatively fixed settings, focusing on patients with a specific severity of depression and using fixed treatment regimens. Building on the confirmed efficacy from those RCTs, the present study expands the scope to include patients with different severity of depression and selects initial treatment regimens based on severity. During the study, treatment regimens will be flexibly adjusted according to changes in patient condition and drug response. The aim is to evaluate the real-world effectiveness of TCM-Western medicine integration based on Shugan Jieyu Capsules under conditions more representative of routine clinical practice, while exploring how to apply Shugan Jieyu Capsules more effectively and conveniently for patients with different severity of depression, thereby providing practical and actionable treatment strategies for clinical use.

Outpatients and inpatients with depression will be recruited. Eligible patients will be enrolled after screening. After enrollment, demographic data will be collected, symptoms and scale scores recorded, and relevant laboratory tests performed. The corresponding treatment regimen will be administered according to the severity of depression. Outcome evaluations will be performed at 4, 8, 12, 16, and 24 weeks of treatment.

Inclusion criteria

• Meet the diagnostic criteria for depression according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5);
• Aged 13-65 years (inclusive), male or female;
• No antidepressants taken within at least 14 days before screening (patients who have received fluoxetine treatment must have discontinued it for at least 28 days before screening);
• Voluntarily sign the informed consent form and comply with all study visits, examinations, and treatments as required by the protocol.

Exclusion criteria

• Treatment-resistant depression (poor clinical response to adequate doses and durations of two or more antidepressants with different mechanisms, or poor clinical response to adequate doses and durations of antidepressant TCMs) or depression induced by psychoactive substances;
• Patients who meet the diagnostic criteria for other mental disorders in the DSM-5 (such as schizophrenia spectrum disorders, bipolar disorder);
• Patients with serious suicidal tendencies (HAMD-17 item 3 score ≥ 3) or homicidal tendencies;
• Patients with severe or unstable cardiovascular, cerebrovascular, hepatic, renal, endocrine, digestive, hematological, or other medical conditions;
• Known or suspected history of allergy to Hypericum perforatum or Eleutherococcus senticosus;
• Pregnant or breastfeeding women;
• Patients currently receiving treatment with any other investigational drug;
• Other patients who are not suitable for participation in this clinical trial.