Treating Depression With Transcutaneous Electrical Cranial-auricular Acupoint Stimulation (TECAS).

Study Overview
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Brief Summary
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One multi-center, randomized controlled clinical trial is designed to examine whether transcutaneous electrical cranial-auricular acupoint stimulation (TECAS) is non-inferior to the antidepressant drug (Escitalopram) in treating mild-to-moderate depression, to evaluate the depressive subtypes who are suitable for the TECAS treatment. To achieve this objective, 470 patients with mild-to-moderate depression will be recruited and assigned to receive TECAS treatment (n =235) or Escitalopram (n =235, 10-20mg/day, q.d.) for 8 weeks. The primary outcome is the Montgomery-Åsberg Depression Rating Scale (MADRS); other outcomes include the17-item Hamilton Depression Scale (HAMD-17), the Hamilton Anxiety Rating Scale (HAMA), Pittsburgh sleep quality index (PSQI), the Short Form 36 Health Survey and TCM diagnosis of depression. In addition, the safety index will be measured throughout the whole study.

Detailed Description
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Depression is a common and costly disorder with high prevalence rate and high suicide rate. Antidepressants are the first-line treatments for depression. However, approximately 50% to 60% of the patients have not achieved adequate response following antidepressant treatment. A large body of evidence well confirms that electro-acupuncture is effective in improving depression and reducing anti-depressant treatment-caused side effects, including pain, nausea, dizziness, fatigue, anxiety and sleep disturbance. Based on the combination of ancient and modern literature and famous traditional Chinese medicine practitioners' experience, the Evidence-based Guidelines of Clinical Practice with Acupuncture and Moxibustion-Depression (ZJ/TE003-2014) recommended Baihui (DU20) and Yintang (DU29) as main acupoints in treating patients with depression via electro-acupuncture. Our research team have completed a series of clinical trials, including electrical stimulation on cranial and auricular acupoints for treating depression, postpartum depression, post-stroke depression, and depression with somatic pain. These studies found that cranial-auricular acupoint stimulation, as well as transcutaneous electrical stimulation, can improve depressive symptoms and accompanying symptoms in patients with depression significantly. Unlike traditional acupuncture, transcutaneous electrical stimulation does not need needles to penetrate the skin. It places electrodes on the skin of the corresponding acupoints. In this way, traumatic pain and fear of acupuncture can be avoided. And it is more easily accepted for patients and more convenient for clinical operation. Therefore, the investigators plan to build a novel transcutaneous electrical stimulation therapy--Transcutaneous electrical cranial-auricular acupoint stimulation (TECAS). In the proposed study, a combination of transcutaneous electrical cranial and transcutaneous electrical auricular acupoint stimulation will be employed to treat patients with mild-to-moderate depression compared with antidepressant Escitalopram, to confirm the clinical effectiveness of TECAS in mild-to-moderate depression.

Official Title
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Effectiveness and Safety of Transcutaneous Electrical Cranial-auricular Acupoint Stimulation (TECAS) for Patients With Mild-to-moderate Depression.

Conditions
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Mild-to-moderate Depression

Intervention / Treatment
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* Procedure: TECAS Procedure
* Drug: Escitalopram
* Drug: Insomnia medication


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary diagnosis as mild to moderate depression； Aged 18-70； A score of MADRS ≥12 and <30 without suicide risk; Participants to give consent and to cooperate with the treatment and data collection; Exclusion Criteria: Pregnant； Patients with severe diseases of heart, brain, liver, kidney or hematopoietic system, patients with acute diseases, infectious diseases and malignant tumours; Patients who are unable to stop taking relevant drugs as required during the trial; (any other drug or non-drug treatment that affects depressive symptoms, including Chinese medicine, western medicine, and physical therapies et al.) Patients with any history of psychosis or mania; Patients with cognitive disorders or personality disorders; Patients with serious suicidal ideation or behaviours.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TECAS<br>Patients will receive transcutaneous electrical cranial-auricular acupoint stimulation (TECAS) daily. | Procedure: TECAS Procedure<br>* Location: Cranial electrical stimulation acupoints: Baihui (DU20) and Yintang (DU29). Auricular electrical stimulation zone: the distribution area of auricular branch of the vagus nerve. Two electrodes electric stimulation at a frequency of 4/20 Hz will be employed on the cranial acupoints and the auricular zone respectively. The TECAS treatment will consistent of two sessions per day (30 minutes) for 8 consecutive weeks.<br>* Other names: TECAS;Drug: Insomnia medication<br>* For patients with severe insomnia, stabilizers and benzodiazepines could be prescribed and must be recorded in the case report form.<br>* Other names: Benzo;|
| Active Comparator: Anti-depressants<br>Each subject shall receive oral administration Escitalopram (10-20mg/day, q.d.), as prescribed by a clinical psychiatrist with respect to patients' conditions for 8 consecutive weeks. | Drug: Escitalopram<br>* Each subject shall receive oral administration Escitalopram (10-20mg/day, q.d.), as prescribed by clinical psychiatrist with respect to patients' conditions for 8 consecutive weeks.<br>* Other names: Escitalopram Oxalate Tablets;Drug: Insomnia medication<br>* For patients with severe insomnia, stabilizers and benzodiazepines could be prescribed and must be recorded in the case report form.<br>* Other names: Benzo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response at the end of treatment | The responder is defined as a ≥50% reduction from the baseline MADRS or HAMD-17 at the end of treatment. | 8 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission at the end of treatment | Remission is defined as a score of 12 or fewer points on the MADRS or as 7 or fewer points on the HAMD-17. | 8 week | 
| Changes from baseline in the Montgomery-Åsberg Depression Rating Scale (MADRS) score | The 10-item Montgomery-Åsberg Depression Rating Scale (MADRS) measures severity of depression in individuals 18 years and older (range, 0 to 60, with higher scores indicating more severe depression; minimal clinically significant difference, 1.6 to 1.9 points). Each item is rated on a 7-point scale. The scale is an adaptation of the Hamilton Depression Rating Scale and has a greater sensitivity to change over time. The scale takes 20 to 30 minutes to complete and score. | Baseline, 2 week, 4 week, 8 week, 12 week | 
| Changes from baseline in the 17-item Hamilton Depression Scale (HAMD-17) | The Hamilton Rating Scale for Depression, abbreviated HDRS, HRSD or HAM-D, measures depression in individuals before, during and after treatment. The scale is administered by a health care professionals and contains 21 items, but is scored based on the first 17 items, which are measured either on 5-point or 3-point scales. It takes 15 to 20 minutes to complete and score. | Baseline, 2 week, 4 week, 8 week, 12 week | 
| Changes from baseline in the Hamilton Anxiety Rating Scale (HAMA) | The HAMA is widely used in both clinical practice and research settings. The scale consists of 14 items, each defined by a series of symptoms, and measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. | Baseline, 2 week, 4 week, 8 week, 12 week | 
| Changes from baseline in the Pittsburgh sleep quality index (PSQI) | The sleep quality will be assessed using the Pittsburgh sleep quality index. Assessments will be conducted at baseline, 2-week and once every four weeks thereafter. | Baseline, 2 week, 4 week, 8 week, 12 week | 
| Changes from baseline in the Short Form 36 Health Survey | The Short Form (36) Health Survey is a 36-item, patient-reported survey of patient health. It has 36 items grouped in 8 dimensions: physical functoning, physicial and emotional limitations, social functioning, bodily pain, general and mental health. | Baseline, 2 week, 4 week, 8 week, 12 week | 
| Adverse events | Adverse events of TECAS treatment will be assessed and would be evaluated during the whole procedure, as well as laboratory tests (whole blood counts, renal and liver functions) if needed. Side Effects of Escitalopram will be assessed and would be evaluated during the whole procedure, as well as laboratory tests (whole blood counts, renal and liver functions) if needed. All clinical adverse events will be recorded in terms of intensity (mild, moderate, or severe), duration, outcome and relationship to the study. | Weeks 1-12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Depression