Effect of XingpiJieyu Formula on Mitochondrial Energy Metabolism in Severe Liver-Stagnation and Spleen-Deficiency Depression.

Research on the Therapeutic Effect and Clinical Indicators of XingpiJieyu Formula in the Treatment of Severe Liver Depression and Spleen Deficiency Type Depression Based on Abnormal Mitochondrial Energy Metabolism Pathway

Study Title: Research on the therapeutic effect and clinical indicators of XingpiJieyu formula in the treatment of severe liver depression and spleen deficiency type depression based on abnormal mitochondrial energy metabolism pathway

Purpose of the Study: (1) Application of XPJYF in the treatment of severe MDD patients for 8 weeks, detection of abnormal mitochondrial energy metabolism and biosynthesis, and exploration of biological markers for the therapeutic effect of XPJYF in the treatment of severe MDD with liver depression and spleen deficiency type. (2) Explore the biological indicators for predicting the antidepressant efficacy of XPJYF in the treatment of severe MDD patients and explore new pharmacological pathways for the combination of traditional Chinese and Western medicine in the treatment of MDD.

To evaluate whether adding Xingpi Jieyu Formula (a traditional Chinese herbal granule) to the standard antidepressant escitalopram improves symptoms in people with severe major depressive disorder (MDD) who also have a specific traditional Chinese medicine pattern called "Liver-Stagnation and Spleen-Deficiency."

Study Design:

100 patients with severe MDD (Liver-Stagnation and Spleen-Deficiency pattern) will be randomly assigned to one of two groups: Test group: Escitalopram + Xingpi Jieyu Formula, Control group: Escitalopram + placebo (identical granules with no active ingredient).

An additional 50 healthy volunteers will serve as a comparison group. Treatment duration: 8 weeks. Double-blind design: neither participants nor study doctors know who receives the real herbal formula or the placebo.

Data Collection Timepoints: Baseline (before treatment), Week 2, and Week 8 (end of treatment). At each timepoint, blood samples and clinical information (e.g., mood ratings, symptom scores) will be collected.

Main Measurements: Blood samples will be tested for markers of mitochondrial energy metabolism (using ELISA). Whole genome testing will be performed in 60 patients (from the MDD groups) and in all 30 healthy volunteers.

Inclusion Criteria: ① Outpatient/inpatient, aged 18-60, right-handed. ② The diagnosis of Western medicine meets the diagnostic criteria of DSM-5 for MDD, as well as the diagnostic criteria for depression and liver depression and spleen deficiency in the 2008 Guidelines for the Diagnosis and Treatment of Common Diseases in Traditional Chinese Medicine issued by the Chinese Society of Traditional Chinese Medicine HAMD-17 score ≥ 18 points, and HAMD-17 item 3 ≤ 2 points

Exclusion Criteria: ① DSM-5, with the exception of MDD, has any current or past diagnosis of Axis I mental disorders (MINI). Or it does not meet the diagnostic criteria for depression and liver depression and spleen deficiency syndrome in the "Diagnosis and Treatment Guidelines for Common Diseases in Traditional Chinese Medicine" issued by the Chinese Society of Traditional Chinese Medicine in 2008. ② Education years<5 years or IQ<90 points. ③ Suicide ideation or suicidal behavior (HAMD-17 item 3>2 points).

Possible Benefits: May offer a new treatment option for patients with severe depression who do not fully respond to standard antidepressants. May help identify blood markers that can predict which patients are most likely to benefit from adding traditional Chinese medicine to their treatment. May improve understanding of how traditional Chinese medicine affects cellular energy metabolism (mitochondria), potentially leading to better treatments for depression.

Risks and Safety: All study medications (escitalopram and Xingpi Jieyu Formula) are already approved for clinical use. Side effects are known and generally mild. Blood draws may cause temporary discomfort or bruising. Participants will be closely monitored by study doctors. If serious side effects occur, the study medication can be stopped and appropriate medical care will be provided. All personal information and test results will be kept confidential.

Study Location and Approval: This study is led by researchers at Peking University Sixth Hospital (and other collaborating centers) and has been approved by the Medical Ethics Committee.

Study Overview

• Status: Completed
• Conditions: Severe Major Depression Disorder; Liver-Stagnation and Spleen-Deficiency
• Intervention / Treatment: Drug: XingpiJieyu Formula (XPJYF) + Escitalopram; Drug: XingpiJieyu Placebo + Escitalopram

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100191
    • Peking University Sixth Hospital
  • Beijing, China
    • Peking University Sixth Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

① Outpatient/inpatient, aged 18-60, right-handed

② The diagnosis of Western medicine meets the diagnostic criteria of DSM-5 for MDD, as well as the diagnostic criteria for depression and liver depression and spleen deficiency in the 2008 Guidelines for the Diagnosis and Treatment of Common Diseases in Traditional Chinese Medicine issued by the Chinese Society of Traditional Chinese Medicine HAMD-17 score ≥ 18 points, and HAMD-17 item 3 ≤ 2 points

Exclusion criteria：

• DSM-5, with the exception of MDD, has any current or past diagnosis of Axis I mental disorders (MINI). Or it does not meet the diagnostic criteria for depression and liver depression and spleen deficiency syndrome in the "Diagnosis and Treatment Guidelines for Common Diseases in Traditional Chinese Medicine" issued by the Chinese Society of Traditional Chinese Medicine in 2008 ② Education years<5 years or IQ<90 points ③ Suicide ideation or suicidal behavior (HAMD-17 item 3>2 points)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: XingpiJieyu Formula + Escitalopram; Patients with severe major depressive disorder (Liver-Stagnation and Spleen-Deficiency pattern according to TCM) receive oral escitalopram (10-20 mg/day) combined with XingpiJieyu Formula granules for 8 weeks.	Drug: XingpiJieyu Formula (XPJYF) + Escitalopram; XingpiJieyu Formula (XPJYF): Traditional Chinese medicine herbal granules. Dosage: 1 sachet (approximately 5 g) taken orally with 200 ml warm water after meals, twice daily. Escitalopram: Selective serotonin reuptake inhibitor (SSRI) tablets. Dosage: 10 mg/day for the first week; after one week, the dose may be increased to 10-20 mg/day based on clinical response and tolerability. Both medications are taken for 8 weeks.
Placebo Comparator: XingpiJieyu Placebo + Escitalopram; Patients with severe major depressive disorder (Liver-Stagnation and Spleen-Deficiency pattern according to TCM) receive oral escitalopram (10-20 mg/day) combined with a matching placebo for 8 weeks.	Drug: XingpiJieyu Placebo + Escitalopram; XingpiJieyu Placebo: Granules identical in appearance, taste, and administration to Xingpi Jieyu Formula but containing no active pharmaceutical ingredients. Dosage: 1 sachet taken orally with 200 ml warm water after meals, twice daily. Escitalopram: Same as Arm 1 (10-20 mg/day for 8 weeks).
No Intervention: Healthy Control; Age- and sex-matched healthy volunteers receive no medication. They undergo the same blood sample collection and clinical assessments at baseline.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SIRT1 and its mRNA in peripheral blood nucleated cells	Detection of SIRT1 and its mRNA in peripheral blood nucleated cells (particularly PBMCs) at the end of 8 weeks treatment from baseline and compared with healthy control on baseline to test biological effectiveness of XPJYF and ESC in the treatment of MDD.	Baseline (week 0), week 2, and week 8
Hamilton Depression Rating Scale, 17 items (HAMD-17) total score changes	One hundred MDD patients with treatment - efficacy as assessed by HAMD - 17 on baseline, at the end of 2 weeks and 8 weeks.	Baseline (week 0), week 2, and week 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TESS for adverse effect rating	TESS assessment was used to evaluate the adverse effects of XPJYF and ESC treatment in 80 patients with MDD at the end of 2 weeks and 8 weeks of treatment, and the difference in total TESS scores between the two MDD groups (40 patients in each group) was compared.	Week 2 and week 8

Collaborators and Investigators

• Sponsor: Peking University Sixth Hospital
• Collaborators: Dongfang Hospital Beijing University of Chinese Medicine; National Institute on Drug Dependence, Peking University

Study record dates

Study Major Dates

• Study Start (Actual): May 23, 2023
• Primary Completion (Actual): January 28, 2026
• Study Completion (Actual): January 31, 2026

Study Registration Dates

• First Submitted: May 1, 2026
• First Submitted That Met QC Criteria: May 8, 2026
• First Posted (Actual): May 15, 2026

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 8, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: mitochondria; Integrated Traditional Chinese and Western Medicine; Liver-Stagnation and Spleen-Deficiency pattern; XingpiJieyu Formula (XPJYF); severe MDD
• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Amines; Nitriles; Propylamines; Benzofurans; Escitalopram
• Other Study ID Numbers: MR-11-23-049173

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No