A Clinical Trial of Fluvoxamine for Melancholia

Study Overview
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Brief Summary
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This study aims at investigating the special effectiveness of antidepressant effect of Fluvoxamine for endogenous depression. The investigators also aim to assess the effect of Fluvoxamine on the multimodal magnetic resonance imaging(MRI), blood cytokines, feces bacteria flora and neuropsychological performance in depression patients with melancholic features. The investigators further aim to identify the predictors of Fluvoxamine's antidepressant effeect using the above techniques.

Detailed Description
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This study aims at investigating the special effectiveness of antidepressant effect of Fluvoxamine for melancholia. The investigators also aim to assess the effect of Fluvoxamine on the multimodal magnetic resonance imaging(MRI), blood cytokines, feces bacteria flora and neuropsychological performance in depression patients with melancholic features. The investigators further aim to identify the predictors of Fluvoxamine's antidepressant effeect using the above techniques.

Official Title
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A Clinical Trial of Fluvoxamine for Melancholia

Conditions
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Depressive Disorder, Endogenous Depression, Melancholia

Intervention / Treatment
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* Drug: Fluvoxamine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult (18-55 years, both sexes), with DSM-4 criteria for MDD without psychosis, as determined by a structured clinical interview Mini International Neuropsychiatric Interview Moderate to severe depression, as defined by a pretreatment score ≥17 on the HDRS-17 scale Informed consent to participate in this study ethinic Han, right-handed, Junior high school education or above Exclusion Criteria: A history of bipolar disorder, schizophrenia, schizoaffective disorder, obsessive-compulsive disorder, panic disorder, or documented Axis II diagnoses; active suicidal intention, as determined by clinical interview Active or recent (<12 months) substance abuse or dependence; excluding nicotine Presence of ECT treatment in recent 6 months period of pregnancy or lactation hearing disorder or colour blindness Immediate relatives have bipolar disorder or mania disorder

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: melancholic depression<br>patients with melancholic depression undergo the treatment of Fluvoxamine | Drug: Fluvoxamine<br>* Fluvoxamine was assigned to be the treatment for the depression patients with melancholic features or not .<br>* Other names: Fluvoxamine Maleate Tablets;|
| Experimental: non-melancholic depression<br>patients with non-melancholic depression undergo the treatment of Fluvoxamine | Drug: Fluvoxamine<br>* Fluvoxamine was assigned to be the treatment for the depression patients with melancholic features or not .<br>* Other names: Fluvoxamine Maleate Tablets;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hamilton Depression Rating Scale-17 item (HAMD-17) | Interview-based questionnaire used to measure the severity of depression. Consists of 17 items with a score calculated. Higher scores are associated with more severe depression. | Baseline, 2weeks, 1 months, 2 months | 
| Change in Hamilton Anxiety Rating Scale-14 item (HAMA-14) | Interview-based questionnaire used to measure the severity of anxiety. Consists of 14 items with a score calculated. Higher scores are associated with more severe anxiety. | Baseline, 1 months, 2 months | 
| Change in voxel-based morphometry of grey matter, white matter as assessed by structural magnetic resonancce imaging | Participants will receive resting-state functional magnetic resonance imaging (MRI). Scans will be performed on a 3.0- T Siemens Magnetom Skyra scanner (Siemens Healthineers, Erlangen, Germany). During scanning, all participants were instructed to remain motionless, and to think of nothing in particular but to not fall asleep. | Baseline, 2 months | 
| Change in Functional connectivity | Change in Functional connectivity of the brain networks as assessed by measure of connectivity in multimodal MRI. | Baseline, 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in peripheral blood cytokines | Peripheral blood sample will be collected and the concentration of IL-6, TNF-α, and CRP will be assessed. | Baseline, 1 months, 2 months | 
| Change in feces bacterial flora | The objective of investigator is to characterize gut microbiome in patients with TRD. To explore the specific diversity of gut microbiome. The stool samples were collected in the collection kits at the baseline, and were frozen at -80 °C. After the process of DNA Purification, 16S rRNA Gene Amplification and Illumina MiSeq sequencing, the study finally find the abundance and diversity of microbiota. | Baseline, 1 months, 2 months | 
| Change in Congruent STROOP Time to Complete (Executive Function) | Stroop Colour Naming Test (STROOP) is a cognitive test designed to assess the ability to inhibit a prepotent response to reading words while performing a task that requires attention control. It comprises two sheets with 50 words on each, and each word is the name of a colour. On the first sheet, the Congruent STROOP Sheet, the word and ink colour match; on the Incongruent STROOP Sheet, the word and ink colour do not match. For each sheet, the patient has 4 minutes to name the ink colour of each word. When the patient finishes the sheet, or once 4 minutes is up, the clinician notes the time taken and counts the number of correct and incorrect responses. The scale ranges from 0-100, the higher score the greater the cognitive flexibility. | Baseline, 1 months, 2 months | 
| Change in DSST (Number of Correct Symbols) | Digit Symbol Substitution Test (DSST) is a cognitive test designed to assess psychomotor speed of performance requiring visual perception, spatial decision-making, and motor skills. It consists of 133 digits and requires the patient to substitute each digit with a simple symbol in a 90-second period. Each correct symbol is counted, and the total score ranges from 0 (less than normal functioning) to 133 (greater than normal functioning). as a description of DSST. | Baseline, 1 months, 2 months | 
| Improvement on Snaith-Hamilton Pleasure Scale (SHAPS) | The Snaith-Hamilton Pleasure Scale (SHAPS) assesses the anhedonia symptoms of MDD patients, with higher score indicating more severe anhedonia. Evaluating the patient's pleasure experience and choosing the degree of agreement with the happy response in some pleasant situations, and each item was rated on a 4-point scale.1 = Strongly agree, 2 = agree, 3 = disagree and 4 = strongly disagree This scale evaluates the status of patients in the recent period of time, The total score of the scale is the sum of the scores of 14 items, with a total score of 14-56. The higher the total score, the more serious the anhedonia. | Baseline, 1 months, 2 months | 
| Young Manic Rating Scale (YMSR) | The YMSR assesses the manic symptoms of the subjects. | Baseline, 1 months, 2 months | 
| Life Event Scale (LES) | The LES assesses the effects of some life events on the subjects. | Baseline, 1 months, 2 months | 
| Beck Scale for Suicide Ideation（BSI） | The BSI assesses the Suicide Ideation of the subjects, including two time points, the latest week and when the subjects were the most depressive. | Baseline, 1 months, 2 months | 
| Hopkins Vocabulary Learning Test-Revised (HVLT-R) | The HVLT-R assesses the memory and the cognition of the subjects. | Baseline, 1 months, 2 months | 
| Sydney Melancholia Prototype Index (SMPI) | The SMPI aims to identify the melancholic and non-melancholic depression. | Baseline, 1 months, 2 months | 
| Generalized Anxiety Disoder-7 (GAD-7) | The GAD-7 aims to assesses the severity of anxious symtoms. | Baseline, 1 months, 2 months | 
| Self-reported Quick Inventory of Depressive Symptomatology (QIDS-SR) Scale | The QIDS-SR assesses the depressive symtoms in latest week of subjects quickly. | Baseline, 1 months, 2 months | 
| Dimensional Anhedonia Rating Scale (DARS) | The DARS assesses different dimensions in Anhedonia of the subjects. | Baseline, 1 months, 2 months | 
| Child Trauma Scale (CTQ) | The CTQ assesses child trauma happen to the subjects. | Baseline, 1 months, 2 months | 
| Sheehan Disability Scale (SDS) | The SDS assesses the impairment in the occupational, familial and social ability of the subjects. | Baseline, 1 months, 2 months | 
| Pittsburgh Sleep Quality Index (PSQI) | The PSQI assesses the sleep quality of the subjects. | Baseline, 1 months, 2 months | 
| Perceived Deficit Questionnaire for Depression (PDQ-D) | The PDQ-D assesses the perceived deficit of the subjects | Baseline, 1 months, 2 months | 
| Medication Adherence Rating Scale (MARS) | The MARS assesses the medication adherence condition of the subjects | 1 months, 2 months | 
| Rating Scale for Side Effects (SERS) | The SERS assesses the side effects of medication condition in the subjects | 1 months, 2 months |