Effect of Electroacupuncture on Treating the First-episode Depression

Study Overview
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Brief Summary
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Depression is a disease that endangers the physical and mental health of all human beings. Only 30-40% of patients with initial episode depression are cured after treatment with antidepressants. Acupuncture is a widely recognized therapy to treat depression in clinical practice, and it can effectively relieve the depressive mood and improve related physical symtoms in patients with mild to moderate depression. This randomised controlled trial (RCT) is aimed to investigate the efficacy and safety of electroacupuncture (EA) in the treatment for patients with the first-episode of mild to moderate depression.

Detailed Description
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Patients will be recruited from the outpatient clinics in Shanghai Municipal Hospital and Shanghai Mental Health Center by Wechat and posters. A total of 204 eligible patients will be randomly allocated to two groups by a randomized block design: the electroacupuncture (EA) group (receiving EA treatment and taking the placebo drugs), and the antidepressants group (receiving sham acupuncture and taking the escitalopram ). After a one-week baseline evalauation, participants will enter a 9-month observation period in this trial, with a 3-month intervention period and a 6-month follow-up period. The interventiuon period will last for 12 weeks, with 3 sessions of real or sham acupuncture treatment per week for the first 8 weeks, and 2 sessions per week for the remaining 4 weeks. The escitalopram or the placebo will be given to the patients at a set time once a week during the 12-week intervention period, with daily oral dose of 10mg or up to 20mg as the maximum dose. Excperts in the Shanghai Mental Health Center will help the participants to adjust the drug dosage during the intervention period. The primary outcome is the 17-item Hamilton Rating Depression Sclae (HRDS-17) at week 12. The secondary outcomes include the recovery rate and the remission rate of depression, the Patient Health Questionnaire(PHQ-9) and the Medical Outcomes Study 36-Item Short Form (SF-36). Adverse effects will be assessed by the Treatment Emergent Symptom Scale through the trial. The software SPSS Version 24.0 for Windows will be used to do the data analysis. All statistical analyses will be based on the intention-to-treat (ITT) population of all randomly assigned patients, with a 2-sided significance level of less than 0.05.

Official Title
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Efficacy and Safety of Electroacupuncture on Treating the First Episode of Mild to Moderate Depression

Conditions
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Depression

Intervention / Treatment
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* Other: electroacupuncture (EA) treatment
* Other: sham acupuncture (SA) treatment
* Drug: Escitalopram 10mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants who meet the diagnostic criteria of depression according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Participants whose HDRS-17 score is 17-25 (mild-to-moderate depression). Participants who suffer from depression for the first time. Patients who have not taken any previous antidepressants. Patients who are assessed as low risk for suicide. Participants who have not received acupuncture treatment for at least 1 year. Participants who voluntarily agree with the investigation and sign a written informed consent form. Exclusion Criteria: Participants with secondary depressive disorders caused by organic diseases, medicine or psychotic disorders. Participants who are in the depressive episode of bipolar disorder, or suffering from dysthymia, reactive depression and depressive syndrome caused by other diseases. Participants who had severe organic brain diseases and other serious physical diseases. Participants with a history of alcohol abuse or drug dependence. Participants who have enrolled in other clinical trial within 1 months. Pregnant or lactating women.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: the electroacupuncture group<br>the electroacupuncture and the placebo drug | Other: electroacupuncture (EA) treatment<br>* The regular acupuncture treatment will be applied at the acupoints including Baihui (GV20), Yintang (GV29), Guanyuan (RN4), Qihai (RN6), bilateral ZuSanli (ST36) and bilateral SanYinjiao (SP6). After needle insertion, rotating or lifting-thrusting manipulation will be applied for 'De qi' sensation. Three pairs of electrodes of the electroacupuncture apparatus will be connected to the needles of GV20 and GV29, and bilateral ST36 and SP6 for 25 minutes, delivering a continuous wave with a frequency of 2-8Hz which is based on the tolerance of each patient. The selection of matching acupuncture points will be determined by the acupuncturist according to the patients' different syndrome patterns.<br>Drug: Placebo<br>* Placebo drugs are tablets of the same color and size as escitalopram tablets, consisting mainly of starch, and will be tested for safety before being used in the trial. The way the medication is dispensed, the details of how the medication is administered, the dosage, and the record of the drug diary are consistent with the application of the real drugs.<br>* Other names: placebo drug application;|
| Placebo Comparator: the drug group<br>the sham acupuncture and the drug Escitalopram | Other: sham acupuncture (SA) treatment<br>* The sham acpunture treatment will be applied at the same acupoints as the EA treatment with the Streitberger placebo needles. When the blunt needle tip of the placebo needles touches the skin, the patient will get a pricking sensation, but there is no real needle inserted into the skin. The electroacupuncture apparatus will be set on the table beside the patients and two pairs of electrodes will be connected to the needles at bilateral ST36 and SP6. Acupuncturists will turn on the apparatus but all indicators will be set to '0'. Participants will be informed when needles are removed after 25 minutes. Acupuncturists will use dry cotton balls to press the skin around the acupoints when withdrawing the needles so that patients can feel the withdrawal of the 'needles'.<br>Drug: Escitalopram 10mg<br>* Escitalopram will be used as the antidepressants for relieving patients' depressive mood. The dose of the drug will be the minimum clinical starting dose of 10 mg once daily, taken orally in the morning, for a period of 3 months. During the intervention period, patients will be allowed to increase the drug dose (up to 20 mg) according to their mental status. Patients will record the details of the drug dose, duration of dosing,responses and possible side effects on a drug dairy. Pateints will receive 7 tablets of escitalopram from an independent dispencer at a set time each week. They may receive additional dose of escitalopram once again during the week if necessary and it will be recorded by the dispenser.<br>* Other names: real drug application;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 17-item Hamilton Depression Rating Scale (HDRS-17) | The HDRS-17 is an observer-rating questionnaire with 17 items used to assess the symptoms of patients diagnosed as suffering from depressive states. Each item is rated in 3-point or 5-point scales. A higher total score indicates a higher depression level. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recovery rate of depression | the percentage of patients with an HDRS-17 score ≤8 | Week 12 | 
| Remission rate of depression | the percentage of patients' HDRS-17 score between 8 and 12 | Week 12 | 
| HDRS-17 | The HDRS-17 is an observer-rating questionnaire with 17 items used to assess the symptoms of patients diagnosed as suffering from depressive states. Each item is rated in 3-point or 5-point scales. A higher total score indicates a higher depression level. | Week 4, week 8, week 16, week 24 and week 36 | 
| Patient Health Questionnaire(PHQ-9) | The PHQ-9 is developed according to the American Diagnostic Criteria for Major Depressive Disorder and is recommended by the WHO as an important tool for screening and assessing the depressive status of patients. It consists of 9 items that are easily and effectively used to understand a subject's depression. The higher the total score indicates the more severe depression. | Week 4, week 8, week 16, week 24 and week 36 | 
| The Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) | It is one of the most widely used quality-of-life assessment scales with good reliability and validity. It provides a comprehensive overview of the participants' level of quality of life in eight dimensions: physiological functioning, physical functioning, somatic pain, general health status, energy, social functioning, emotional functioning, and mental health. A combination of item response(s) is then aggregated to calculate a score for each of the eight dimensions. The scores for each dimension range from 0 to 100, with higher scores indicating better health status. | Week 4, week 8 and week 12 | 
| Drug dairy | A drug record booklet will be issued by the study staff to each patients, and the participants will be asked to record the actual dose, frequency, time of taking drug or side effects everyday. | Up to 12 weeks | 
| Adverse events（AEs） | Adverse events (AEs) in the trial includes any abnormal events and all types of medical events that were clearly or suspected to be related to the real and sham acupuncture treatment or the drug. Patients may occur focal skin infections, subcutaneous hematomas, and dizziness during the acupuncture treatment, or exacerbation of the condition due to excessive treatment stimulation. AEs including sedation, dizziness, sleep disorders, or constipation due to the drug will be recorded as well. Cold, trauma, or other medical events that resulted in hospitalization during the trial will be also included as AEs. | Up to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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first-episode depression, electroacupuncture, anti-depressants, sham acupuncture, placebo drugs, randomized controlled trial