Study on the Optimal Diagnosis and Treatment Strategy of Major Depressive Disorder Based on Anhedonia

Study Overview
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Brief Summary
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This study is a multicenter clinical research and focuses on the exploring of optimal diagnosis and treatment strategies of MDD based on anhedonia.

Detailed Description
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Major depressive disorder (MDD) is a heterogeneious psychiatric disorder with complex etiology and pathogenesis. The lack of objective criteria for diagnosis and the use of trial-and-error treatment strategy are the current challenge. Anhedonia is the core symptom of MDD and the aberrant reward system and abnormal inflammatory immune may be the pathological mechanisms. Previous evidence suggests anhedonia cannot be improved quickly and efficiently by taking the first-line antidepressants. This study focuses on exploring the optimal diagnosis and treatment strategy for MDD patients with anhedonia. Based on the hypothesis of inflammatory-immune system，neurotransmitter abnormalities and aberrant reward system, this study aims to evaluate the efficacy and safety of the combinations of escitalopram and aripiprazole and/or omega-3 polyunsaturated fatty acids for MDD patients with anhedonia with a factorial design. Moreover, the multidimensional data including the clinicopathological features, neuroimaging data and inflammatory cytokines will be used to establish the model of diagnosis and treatment strategy.

Official Title
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Study on the Optimal Diagnosis and Treatment Strategy of Major Depressive Disorder Based on Anhedonia

Conditions
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Outpatients / Inpatients With Depression

Intervention / Treatment
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* Drug: Escitalopram
* Drug: Escitalopram+Aripiprazole
* Drug: Escitalopram+omega-3 PUFAs
* Drug: Escitalopram+Aripiprazole+omega-3 PUFAs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Major depressive disorder according to Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-5); Age: 18-55 (including 18 and 55) HAMD-17≥18 DARS ≤ 28 Do not receive repetitive Transcranial Magnetic Stimulation (rTMS) or modified electroconvulsive therapy (MECT) treatment in past six months. Sign the informed consent form voluntarily and agree to participate in all visits, examinations and treatment as required by the trial protocol. Exclusion Criteria: Patients who are diagnosed with major somatic diseases; Patients who meet DSM-5 diagnostic criteria for other mental disorders: Personality disorder, mental retardation; drug and/or alcohol dependence; Patients with severe suicidal tendencies or suicidal behavior; Pregnant or lactating women; Patients with MRI contraindications; Patients who are regarded as unsuitable by investigators for this clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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: Escitalopram<br>Escitalopram monotherapy (10-20 mg/day） | Drug: Escitalopram<br>* Escitalopram<br>|
| Experimental: Escitalopram + omega-3 PUFAs<br>Escitalopram (10-20 mg/day）combined with omega-3 PUFAs （EPA 900mg，DHA 300 mg） | Drug: Escitalopram+omega-3 PUFAs<br>* Escitalopram+omega-3 PUFAs<br>|
| Experimental: Escitalopram + Aripiprazole<br>Escitalopram (10-20 mg/day）combined with Aripiprazole （2.5-10 mg/day) | Drug: Escitalopram+Aripiprazole<br>* Escitalopram+Aripiprazole<br>|
| Experimental: Escitalopram + omega-3 PUFAs + Aripiprazole<br>Escitalopram (10-20 mg/day）combined with omega-3 PUFAs （EPA 900mg，DHA 300 mg）and Aripiprazole （2.5-10 mg/day) | Drug: Escitalopram+Aripiprazole+omega-3 PUFAs<br>* Escitalopram+Aripiprazole+omega-3 PUFAs<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The improvement of anhedonia after 8-week treatment | The change value of Dimensional Anhedonia Rating Scale (DARS) total score after 8-weeks treatment compared to that at the baseline. The maximum score of DARS total score is 68 and the minimum is 0. Higher scores mean a better outcome. | Day 0 to Day 56 | 
| The improvement of depressive symptoms after 8-week treatment | The change value of 17-item Hamilton depression rating scale (HAMD-17) total score after 8-weeks treatment compared to that at the baseline. The maximum score of HAMD-17 is 51 and the minimum is 0. Higher scores mean a worse outcome. | Day 0 to Day 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The improvement of anhedonia at early timepoints during the treatment procedure | The outcome is measured by Dimensional Anhedonia Rating Scale (DARS) total score. The change value of DARS total scores at early time points compared to that at the baseline. The maximum score of DARS total score is 68 and the minimum is 0. Higher scores mean a better outcome. | Day 0 to Day 14, Day 0 to Day 28 | 
| The improvement of depressive symptoms at early timepoints during the treatment procedure | This outcome is measured by 17-item Hamilton depression rating scale (HAMD-17) total score. The change value of HAMD-17 total scores at early time points compared to that at the baseline. The maximum score of HAMD-17 is 51 and the minimum is 0. Higher scores mean a worse outcome. | Day 0 to Day 14, Day 0 to Day 28 | 
| The improvement of anxiety symptoms | The outcome is measured by Hamilton anxiety rating scale (HAMA) total score change. The change value of HAMA total scores at each timepoints compared to the baseline. The maximum score of HAMA is 56 and the minimum is 0. Higher scores mean a worse outcome. | Day 0 to Day 14, Day 0 to Day 28, Day 0 to Day 56 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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major depressive disorder, anhedonia, inflammatory immune, reward system, optimal treatment, neurotransmitter