Multi-Dimensional Diagnosis,Individualized Therapy,and Management Technique for Major Depressive Disorder:Based on Clinical and Pathological Characteristics (STEP-MDD)

Multi-dimensional Diagnosis,Individualized Therapy,and Management Technique for Major Depressive Disorder:Based on Clinical and Pathological Characteristics

Major Depressive Disorder is one of the most common mental diseases,which increases health-care costs and the financial burden to families and societies. Considering its complex clinical symptoms and diversity of comorbidity, depressive disorder's recognition，diagnosis，and antihistone are based on symptomatology,which is lack of multidimensional diagnosis technique based on clinical pathological characteristics,as well as lack of individualized therapy strategy based on quantified evaluation. Besides, other physical diseases，such as nervous system diseases, cardiovascular diseases，endocrine diseases, have the high comorbidity of depressive disorder. However，there is no precise diagnosis technique or standardized therapy strategy. With all those taken into consideration,our study is aimed to adopt E-mental health and m-Health to explore multi-dimensional diagnosis, individualized therapy and management technique based on molecular biology,nerve electrophysiology，and neuroimaging technology etc.

Study Overview

• Status: Unknown
• Conditions: Depressive Disorder
• Intervention / Treatment: Drug: Fluoxetine; Combination product: fluoxetine + cognitive-behavioral treatment（CBT）; Drug: fluoxetine + Amfebutamone; Combination product: physical treatment+fluoxetine+amfebutamone; Drug: Fluvoxamine; Combination product: Cognitive behavior treatment +fluvoxamine; Drug: Lithium+fluvoxamine; Combination product: fluvoxamine + lithium + physical therapy; Drug: Mirtazapine/SNRIs; Combination product: mirtazapine+ Cognitive behavior treatment; Drug: mirtazapine + SNRIs; Combination product: mirtazapine + SNRIs + physical therapy; Other: TAU(treat as usual)

Detailed Description

Four parts included in our study:

Part 1:The research, development and verification of indicators based on biomarkers and clinical characteristics to guide the diagnosis and treatment of depressive disorders

1. to screen biomarkers, to explore its pathophysiology, and to analyze the correlation between clinical subtypes/characteristics and biomarkers.
2. To differentiate the subtypes of depressive disorder（depression/underload, atypical, anxiety/somatization) based on clinical symptoms and clinical assessement.
3. To establish personalized therapy strategies,and to explore tool kits for diagnosis and treatment based on biomarkers and clinical characteristics.
4. to choose appropriate indicators to monitor therapy and side effect by collecting and analyzing blood/imaging/neuropsychological data.

Part 2: The development,transition and application of hierarchical model diagnostic technique for physical diseases combined with depressive disorder.

1. to recruit patients with physical diseases combined with depressive disorder, and explore potential biomarkers.
2. To chose appropriate therapy strategies based on measurement based care（MBC）, providing hierarchical model diagnostic technique for patients.
3. To weigh therapy efficiency and adverse effect among different medicine therapy groups.

Part3: The development and application of comprehensive prevention， diagnosis,and intervention model of depressive disorder.

1. To explore and establish online screening and assistant diagnosis system for patients with depressive disorder.
2. research ,development and application of intelligent e-MBC. Part 4: The development,transition and application of e-MBC sharing platform.

• Study Type: Interventional
• Enrollment (Anticipated): 800
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • ShanghaiMHC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• aged 18-65 years;
• clinical diagnosis of major depressive disorder;
• 17-Hamilton Depression Scale>20;
• 14-Hamilton Anxiety Scale score<7;
• outpatient treatment;
• first episode;
• medication-naive;

Exclusion Criteria:

• clinical diagnosis of schizophrenia, schizoaffective disorder;
• any prescription or psychotropic medications in the past 4 week;
• serious medical or neurological illness;
• current pregnancy or breastfeeding.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Depression/underload 1; This group would be treated with fluoxetine from the minimum dosage.	Drug: Fluoxetine; Fluoxetine is one kind of selective serotonin reuptake inhibitor(SSRIs), whose effect is much better than other non-underload subtypes compared with underload subtypes.So patients would be treated with fluoxetine only.
Experimental: Depression/underload 2; This group would be treated with fluoxetine combined with cognitive behavior treatment	Combination product: fluoxetine + cognitive-behavioral treatment（CBT）; the investigators would recommend fluoxetine to help to cure depressive disorder.And CBT is a very effective way for patients to alleviate or relieve clinical symptoms during episode stage.
Experimental: Depression/underload 3; This group would be treated with fluoxetine and amfebutamone from the minimum dosage.	Drug: fluoxetine + Amfebutamone; Amfebutamone is one kind of SNRIs, and it shows much better therapy effect on patients with exhaustion /dizziness.So the investigators recommend these two drugs to help to cure patients with depressive disorder.
Experimental: Depression/underload 4; This group would be treated with fluoxetine + physical treatment to help to cure depressive disorder.	Combination product: physical treatment+fluoxetine+amfebutamone; the investigators recommend drug(fluoxetine and amfebutamone) and physical treatment as intervention.
Experimental: Atypical 1; This group would be treated with fluvoxamine from the minimum dosage.	Drug: Fluvoxamine; Fluvoxamine could inhibit CYP1A2 and CYP2C19 and affect the metabolism of melatonin, and help to release symptoms of depressive disorder with sleep problems.
Experimental: Atypical 2; This group would be treated with fluoxetine + cognitive behavior treatment	Combination product: Cognitive behavior treatment +fluvoxamine; the investigators recommend behavioral therapy as well as drugs.
Experimental: Atypical 3; This group would be treated with fluvoxamine + lithium from the minimum dosage.	Drug: Lithium+fluvoxamine; the investigators recommend lithium as a mood stabilizer and use fluvoxamine to affect the level of melatonin.
Experimental: Atypical 4; This group would be treated with fluvoxamine + lithium + physical treatment	Combination product: fluvoxamine + lithium + physical therapy; the investigators recommend depressants and mood stabilizers as well as physical therapy to help to cure depressive disorder.
Experimental: Anxiety/somatization 1; This group would be treated with mirtazapine/selective serotonin-norepinephrine reuptake inhibitors（SNRIs） from the minimum dosage.	Drug: Mirtazapine/SNRIs; Mirtazapine is one kind of antagonist of a2 adrenergic receptors and could block 5-hydroxytryptamine2 and 5-hydroxytryptamine3,help to release symptoms like anxiety or somatization.Besides, SNRIs could also make similar effect on patients.Therefore, the investigators recommend mirtazapine/SNRIs to treat patients with depressive disorder.
Experimental: Anxiety/somatization 2; This group would be treated with mirtazapine/SNRIs + cognitive behavior treatment.	Combination product: mirtazapine+ Cognitive behavior treatment; the investigators recommend CBT and mirtazapine as interventions.The dosage and frequency would depend on patients' severity of symptoms .
Experimental: Anxiety/somatization 3; This group would be treated with mirtazapine + SNRIs from the minimum dosage.	Drug: mirtazapine + SNRIs; the investigator recommend mirtazapine and SNRIs to treat patients with major depressive disorder.
Experimental: Anxiety/somatization 4; This group would be treated with mirtazapine + SNRIs + physical treatment.	Combination product: mirtazapine + SNRIs + physical therapy; the investigators would manage to use drugs and physical treatment to help to release the symptoms of depressive disorder.
Experimental: treatment as usual(TAU); The investigators recommend therapy strategies according to accessible methods.	Other: TAU(treat as usual); patients in this group would receive therapy strategies according to their symptoms and preference.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in levels of microRNA，apolipoproteins, meta ion (Composite measure)	The potential biomarkers in our study include microRNA,apolipoproteins,metallic ion etc.We use quantitative analysis technique to test miRNA,proteins and metallic ion by patients' blood and urines before interventions and after interventions.	at 2,4,6,8,12 week.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hamilton Depression Scale(HADA) scores,reductive ratio	HADA,created by Hamilton in 1960,is one of the most common questionnaires to evaluate the severity of depression and the efficiency of medicine. we adopt the Hamilton Depression Scale(HADA)to evaluate different medicines efficiency by analyzing reductive ratio.The investigators record the total scores of HADA at baseline and 2,4,6,8,12 week.	at 0,2,4,6,8,12 week.
Patient health questionnaire(PHQ-9):the clinical remission ratio	PHQ-9 is a self-report scale composed of 9 items to evaluate the state of depression.The investigators in our study record the total scores of PHQ-9 at 0,2,4,6,8,12 week to analyze the clinical remission ratio.	change from baseline PHQ-9 total scores at 2,4,6,8,12 week
life event scale(LES)	LES is one of the common questionnaires to evaluate individual's mental and stress stimulation in daily life.The investigators record the total scores of LES at baseline.	at baseline
social support scale(SSS)	SSS is one of the common questionnaires to evaluate individual's social support and social relationship network to explore the correlation between social support and mental health. the investigators in our study record the total scores of SSS at baseline.	at baseline
dysfunctional attitudes scales(DAS)	The DAS is a self-report scale composed of 40 items to assess typical, stable depressogenic attitudes or schemas that make individuals vulnerable to depression. The investigators in our study record the total scores od DAS at baseline.	at baseline
the gray matter volume,	The investigators in our study use voxel-based morphometry (VBM8)to record the gray matter volume.	change from baseline neuroimaging data at 2,4,6,8,12 week
fractional amplitudes of low-frequency fluctuation(fLAFF)	The investigators in our study use region-of-interest(ROI)to record fLAFF.	change from baseline neuroimaging data at 2,4,6,8,12 week
Neuroelectrophysiological examination: electroencephalogram(EEG)	EEG is used to record individual's brain activity. The investigators in our study record individual's brain wave.	at baseline
Neuroelectrophysiological examination:electrocardiograph(ECG)	ECG is used to record the individual's cardiac cycle.	at baseline.

Collaborators and Investigators

• Sponsor: Shanghai Mental Health Center
• Collaborators: First Affiliated Hospital Xi'an Jiaotong University; Chinese Academy of Sciences; Shanghai Jiao Tong University School of Medicine; Air Force Military Medical University, China; Renmin Hospital of Wuhan University; Central South University; Wuhan Mental Health Centre; Zhejiang University; The First Affiliated Hospital of Kunming Medical College; Second Military Medical University; Peking University Sixth Hospital; Shanxi Medical University; Corning Hospital, Shenzhen City; the First Specialized Subject Hospital of Harbin; Seventh People's Hospital of Hangzhou; Shandong Mental Health Center

Publications and helpful links

General Publications

• Liu H, Wu X, Wang Y, Liu X, Peng D, Wu Y, Chen J, Su Y, Xu J, Ma X, Li Y, Shi J, Yang X, Rong H, Forti MD, Fang Y. TNF-alpha, IL-6 and hsCRP in patients with melancholic, atypical and anxious depression: an antibody array analysis related to somatic symptoms. Gen Psychiatr. 2022 Sep 8;35(4):e100844. doi: 10.1136/gpsych-2022-100844. eCollection 2022.
• Wang Y, Liu X, Peng D, Wu Y, Su Y, Xu J, Ma X, Li Y, Shi J, Cheng X, Rong H, Fang Y. A Preliminary Study of Different Treatment Strategies for Anxious Depression. Neuropsychiatr Dis Treat. 2022 Jan 4;18:11-18. doi: 10.2147/NDT.S320091. eCollection 2022.
• Liu X, Wang Y, Peng D, Zhang H, Zheng Y, Wu Y, Su YA, Liu M, Ma X, Li Y, Shi J, Cheng X, Rong H, Fang Y. The Developmental and Translational Study on Biomarkers and Clinical Characteristics-based Diagnostic and Therapeutic Identification of Major Depressive Disorder: Study Protocol for a Multicenter Randomized Controlled Trial in China. Neuropsychiatr Dis Treat. 2020 Oct 9;16:2343-2351. doi: 10.2147/NDT.S271842. eCollection 2020.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2017
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: May 7, 2017
• First Submitted That Met QC Criteria: July 12, 2017
• First Posted (Actual): July 17, 2017

Study Record Updates

• Last Update Posted (Actual): October 10, 2017
• Last Update Submitted That Met QC Criteria: October 8, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: MBC; depressive disorder; multi-dimensional diagnosis technique; individualized therapy; management technique; e-MBC
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Pathologic Processes; Mood Disorders; Depression; Depressive Disorder; Disease; Depressive Disorder, Major; Physiological Effects of Drugs; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Tranquilizing Agents; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Dopamine Agents; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Anti-Anxiety Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Antimanic Agents; Cytochrome P-450 CYP2D6 Inhibitors; Serotonin 5-HT3 Receptor Antagonists; Dopamine Uptake Inhibitors; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Cytochrome P-450 CYP1A2 Inhibitors; Adrenergic alpha-Antagonists; Adrenergic alpha-2 Receptor Antagonists; Cytochrome P-450 CYP2C19 Inhibitors; Bupropion; Lithium Carbonate; Mirtazapine; Fluoxetine; Fluvoxamine; Serotonin and Noradrenaline Reuptake Inhibitors
• Other Study ID Numbers: 2016YFC1307100

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: To share raw data via the network platform named Clinical Trial Management Public Platform within 1year after the trial finished. And the platform website address is http://www.medresman.org

Drug and device information, study documents

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