Efficacy and Safety of Intradermal Acupuncture for Major Depressive Disorder

Efficacy and Safety of Intradermal Acupuncture for Major Depressive Disorder: a Study Protocol for a Multicenter, Prospective, Randomized Controlled Trial

Major depressive disorder (MDD) is a common mental illness that severely affects the health and quality of life of patients. Treatment with acupuncture alone or a combination of appropriate adjuncts has been reported to be significantly effective in reducing the severity of MDD, relieving patients' somatic symptoms and improving sleep. This study will focus on the intradermal acupuncture, which is more convenient, gentler and has longer lasting effects. The aim is to study the efficacy and safety of intradermal acupuncture for MDD, and to preliminarily explore the central nervous mechanisms by which it exerts its therapeutic effects.

Study Overview

• Status: Recruiting
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: SSRIs; Procedure: SIA; Procedure: AIA

Detailed Description

A total of 90 patients with MDD who meet the inclusion criteria will be included in the study. Participants will be randomly assigned 1:1:1 to the waiting list group (patients in this group will be treated with selective 5-hydroxytryptamine reuptake inhibitors (SSRIs) only), sham intradermal acupuncture combined with SSRIs (SIA) group and active intradermal acupuncture combined with SSRIs (AIA) group. The study will assess the efficacy and safety of intradermal acupuncture for MDD and examine whether intradermal acupuncture reduces side effects and improves the efficacy of SSRIs for MDD. In addition, the study will use magnetic resonance imaging (MRI) to study the possible central mechanisms by which intradermal acupuncture exerts its antidepressant effects.

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Recruiting
      • the Third Affiliated Hospital of Zhejiang Chinese Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients diagnosed with MDD according to the International Classification of Disease-10 (ICD-10);
2. Aged between 18 and 60 years (no limitation on gender);
3. No depression-related treatment in the past two weeks, except SSRIs;
4. Patients undergoing MRI and MRS should be right-handed and free of traumatic brain injury, claustrophobia or metal implants;
5. Written informed consent is obtained by the person or guardian.

Exclusion Criteria:

1. ICD-10 diagnoses: schizophrenia, bipolar disorder, manic episode or other psychotic disorders; alcohol and drug addiction;
2. Significant skin lesions, severe allergic diseases, tumors, and severe or unstable internal diseases involving the cardiovascular, digestive, endocrine, or hematological system;
3. Acute suicidal tendency;
4. Allergy to adhesive tape and fear of intradermal acupuncture;
5. Pregnancy and lactation;
6. Mental retardation and difficult to cooperate with doctors.
7. Participating in other clinical trials.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Waiting list group; This group will include 30 patients with MDD who will be treated with oral SSRIs only, the dosage of which will be determined by the psychiatrist. After 6 weeks, patients could choose 6 weeks' intradermal acupuncture treatments free of charge.	Drug: SSRIs; SSRIs antidepressants, including fluoxetine, paroxetine, sertraline, citalopram, etc., will be administered at oral doses determined by the psychiatrist. Once daily for 6 weeks.; Other Names: selective 5-hydroxytryptamine reuptake inhibitors
Sham Comparator: SIA+SSRIs group; This group will include 30 patients with MDD who will be treated with sham intradermal acupuncture combined with SSRIs. Acupoints related to MDD will be stimulated by acupuncturists and the dosage of oral SSRIs will be determined by the psychiatrist.	Drug: SSRIs; SSRIs antidepressants, including fluoxetine, paroxetine, sertraline, citalopram, etc., will be administered at oral doses determined by the psychiatrist. Once daily for 6 weeks.; Other Names: selective 5-hydroxytryptamine reuptake inhibitors; Procedure: SIA; This study will select 4 acupoints (all taken bilaterally) commonly used to treat MDD, namely Taichong (LR3), Neiguan (PC6), Sanyinjiao (SP6) and Shenmen (HT7). The SIA will use the same size, colour and material as the AIA with a thin silicone pad in the middle instead of the needle body. SIA will be attached to the acupoints and retained for 72 hours, removed and rested for one day. A total of 10 sessions will be performed over a period of 6 weeks.; Other Names: sham intradermal acupuncture
Experimental: AIA+SSRIs group; This group will include 30 patients with MDD who will be treated with active intradermal acupuncture combined with SSRIs. Acupoints related to MDD will be stimulated by acupuncturists and the dosage of oral SSRIs will be determined by the psychiatrist.	Drug: SSRIs; SSRIs antidepressants, including fluoxetine, paroxetine, sertraline, citalopram, etc., will be administered at oral doses determined by the psychiatrist. Once daily for 6 weeks.; Other Names: selective 5-hydroxytryptamine reuptake inhibitors; Procedure: AIA; This study will select 4 acupoints (all taken bilaterally) commonly used to treat MDD, namely Taichong (LR3), Neiguan (PC6), Sanyinjiao (SP6) and Shenmen (HT7). Depending on acupoints' location, a φ0.20*1.5mm or φ0.20*1.2mm AIA will be selected. Press the AIA to insert it vertically into the acupoint and retain it in the skin. AIA will be retained for 72 hours with a day's rest after removal. During the period of needle retention, participants will be instructed to press the AIA 3-4 times a day for approximately 1 minute each time, with as much stimulation as the patient can tolerate, at intervals of approximately 4 hours. A total of 10 sessions will be performed over a period of 6 weeks.; Other Names: active intradermal acupuncture

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the Hamilton Depression Scale-17 (HAMD-17) Scores	The HAMD scale is the most commonly used in the clinical assessment of depression, including 17 items. The higher the score, the more severe the depression. 0-7 means no depressive symptoms, 8-17 means mild depression, 18-24 was divided into moderate depression, and 25-52 was divided into severe depression.	Baseline, 3 weeks after treatment, 6 weeks after treatment, at 4-week follow-up.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the Self-Rating Depression Scale (SDS) Scores	The standard score is the total of all scores multiplied by 1.25 to the nearest whole number on this scale, which has 20 questions. A standard score below 50 is normal; 50-60 is mild depression; 61-70 is moderate depression; 70 or more is severe depression.	Baseline, 3 weeks after treatment, 6 weeks after treatment, at 4-week follow-up
Changes in the Pittsburgh Sleep Quality Index (PSQI) Scores	The PSQI is used to assess the sleep quality of the participant in the last 1 month and consisted of 19 self-rated and 5 other rated items. The higher the score, the worse the sleep quality. Sleep quality is divided into 4 levels according to the total score.	Baseline, 3 weeks after treatment, 6 weeks after treatment, at 4-week follow-up
Changes in the Treatment Emergent Symptom Scale (TESS) Scores	The TESS is often used to assess the side effects of drugs. It contains 35 symptom items and 2 total assessment items, including behavioural toxicity, laboratory tests, autonomic nervous system, nervous and cardiovascular system, etc. Each of these symptoms is graded into 5 levels of severity (0-4), with the higher the score the more severe the side effects.	Baseline, 6 weeks after treatment
Adverse Events	Adverse events such as bleeding, haematoma, or unbearable pain caused by the needle, as well as drug-induced nausea, vomiting or dizziness, will all be recorded.	Up to 10 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Magnetic resonance imaging (MRI) data acquisition	Brain MRI will be taken by the 3.0 T magnetic resonance scanner to analyse the functional connectivity of the patient's brain regions, particularly the hypothalamus, before and after the intervention.	Baseline, 6 weeks after treatment
Magnetic resonance spectroscopy (MRS ) data acquisition	MRS will be taken by the 3.0 T magnetic resonance scanner to detect the neurometabolic change in patients' brain regions, particularly the hypothalamus, before and after the intervention.	Baseline, 6 weeks after treatment
Blood samples biobank establishment	Blood samples will be collected to test the function of the hypothalamic-pituitary-adrenal axis, including the level of adrenocorticotropic hormone (ACTH) and cortisol (Cor).	Baseline, 6 weeks after treatment

Collaborators and Investigators

• Sponsor: Xiaomei Shao
• Collaborators: First People's Hospital of Hangzhou; The First Affiliated Hospital of Zhejiang Chinese Medical University; Zhejiang Provincial Tongde Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Anticipated): December 30, 2025
• Study Completion (Anticipated): December 30, 2025

Study Registration Dates

• First Submitted: August 31, 2022
• First Submitted That Met QC Criteria: November 2, 2022
• First Posted (Actual): November 3, 2022

Study Record Updates

• Last Update Posted (Actual): November 3, 2022
• Last Update Submitted That Met QC Criteria: November 2, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: Magnetic Resonance Imaging; Major Depressive Disorder; Intradermal Acupuncture
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Disease; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Serotonin Agents; Serotonin Receptor Agonists; Serotonin
• Other Study ID Numbers: 2022ZX010-INM

Drug and device information, study documents

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