A Study of Individualized Diagnosis and Treatment for Major Depressive Disorder With Atypical Features

The lifetime prevalence of major depressive disorder (MDD) is 10%~20%. Worldwide, nearly 340 million individuals have suffered the torture of depression. World Health Organization has reported that MDD would become the most serious global burden of disease and eventually turn into a public health problem in 2030. Varied clinical symptoms, inappropriate treatment, unclear pathogenesis, and lack of recurrent risk early-warning predictors cause a series of clinical problems, such as low diagnostic rate, low effective treatment rate, and high recurrent rate. Hence, this study aims to search multidimensional markers for early diagnosis of MDD, to establish optimized personalized therapy, and to explore sensitive recurrence predictors.

Based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), MDD is subdivided into eight different clinical specifiers, one of which the incident rate of MDD with atypical features reaches 30%~38%. However, there is still a lack of meta-evidence for the clinical treatment strategy in MDD with atypical features. And 45.4 percentage of MDD with atypical features convert to bipolar disorder. Therefore, this study will focus on three issues about what's the objective endophenotype in MDD with atypical features, how to select appropriate personalized treatment for MDD with atypical features, what's the predictive biomarker of conversion to bipolar disorder.

Based on the investigators' previous findings, this study will investigate adult depression at a cross-sectional study and a prospective cohort study. Multivariate informatics analysis was performed from three research dimensions (cognitive neuropsychology, metabonomics, and multimodal neuroimaging), including atypical features, "cold/hot" cognition assessment, KP (kynurenine pathway) metabolomics and inflammatory factors, multimodal MRI robust property. Referring guidelines for the diagnosis and treatment of depression and evidence-based medicine evidence, MDD with atypical features are divided into f groups (antidepressants, antidepressants+mood stabilizers, mood stabilizers, treat as usual). Then, the investigators perform follow-up to verify optimized treatment strategies and to explore risk factors of conversion from MDD with atypical features to bipolar disorder. Furthermore, this study performs correlation analysis to analyze cross-omics data, weight coefficient analysis to analyze multidimensional indexes, clustering analysis to analyze multivariate bio-information data, and artificial intelligence technologies (such as pattern recognition, and machine learning) to realize the transformation from medical data to practical transformation. Eventually, this study builds three specific models (the multidimensional early diagnosis models for MDD with atypical features, the optimized personalized therapy model, and the recurrence and conversion risk early-warning model), which form the integrated intelligent platform for multidimensional diagnosis, personalized treatment, recovery management of MDD with atypical features.

Study Overview

• Status: Unknown
• Conditions: Major Depressive Disorder
• Intervention / Treatment: Drug: SSRIs/SNRIs (Selective Serotonin Reuptake Inhibitors/ Serotonin and Norepinephrine Reuptake Inhibitors); Drug: SSRIs/SNRIs+Mood Stabilizer; Drug: SSRIs/SNRIs+Quetiapine; Drug: Usual Treatment

• Study Type: Interventional
• Enrollment (Anticipated): 780
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Daihui Peng, MD. PhD.; Phone Number: 18017311136; Email: pdhsh@126.com

Study Locations

• China
  • Guangdong
    • Guanzhou, Guangdong, China, 510000
      • Not yet recruiting
      • Guangzhou Psychiatric Hospital
      • Contact: Guiyun Xu, MD; Phone Number: 18922165291; Email: 13650774898@163.com
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Not yet recruiting
      • Wuhan Mental Health Center
      • Contact: Yi Li, MD; Phone Number: 13554013182; Email: psylee@163.com
  • Liaoning
    • Dalian, Liaoning, China, 116000
      • Not yet recruiting
      • Dalian Seventh People's Hospital
      • Contact: Shoufu Xie, MD; Phone Number: 13998622066
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Recruiting
      • Shanghai Mental Health Center
  • Shanxi
    • Xian, Shanxi, China, 710000
      • Not yet recruiting
      • Fourth Military Medical University
      • Contact: Huaning Wang, MD; Phone Number: 13609161341; Email: 13609161341@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 58 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 16-60 years old;
2. Meeting with the criteria of major depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5;
3. Scored 20 or higher on the Hamilton's Depression Scale with 24 items (HAMD-24);
4. With enough audio-visual ability and comprehensive ability to accomplish the visits;
5. Be necessary and suitable to accept the treatment of antidepressants;
6. Scored less than 14 on Hamilton's Anxiety Scale (HAMA) and scored less than 14 on the Hypomania Symptom Checklist-32 (HCL-32);
7. With 2 or more atypical symptoms including significant weight gain or increase in appetite, hypersomnia, leaden paralysis, and a long-standing pattern of interpersonal rejection sensitivity that results in significant social or occupational impairment.

Exclusion Criteria:

1. Severe medical or neurological problems;
2. Previous mania or hypomania episodes;
3. Female patients who are pregnant, planning to be pregnant or breastfeeding;
4. Actively suicide ascertained by research psychiatrist or 3rd item of HAMD scored≥3(suicidality);
5. Had ECT, MECT or rTMS in the past 6 months;
6. Experienced severe personality disorder, mental retardation, anorexia/bulimia nervosa.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FAD; the first-episode major depressive disorder with atypical feature	Drug: SSRIs/SNRIs (Selective Serotonin Reuptake Inhibitors/ Serotonin and Norepinephrine Reuptake Inhibitors); Patients will be treated with Selective Serotonin Reuptake Inhibitors/ Serotonin and Norepinephrine Reuptake Inhibitors.; Drug: SSRIs/SNRIs+Mood Stabilizer; Patients will be treated with Mood Stabilizer combined with Selective Serotonin Reuptake Inhibitors/ Serotonin and Norepinephrine Reuptake Inhibitors.; Drug: SSRIs/SNRIs+Quetiapine; Patients will be treated with Quetiapine combined with Selective Serotonin Reuptake Inhibitors/ Serotonin and Norepinephrine Reuptake Inhibitors.; Drug: Usual Treatment; Patients' treatment will be decided by the clinical doctor.
Experimental: RAD; the recurrent major depressive disorder with atypical feature who have been medication-free for no less than 2 weeks	Drug: SSRIs/SNRIs (Selective Serotonin Reuptake Inhibitors/ Serotonin and Norepinephrine Reuptake Inhibitors); Patients will be treated with Selective Serotonin Reuptake Inhibitors/ Serotonin and Norepinephrine Reuptake Inhibitors.; Drug: SSRIs/SNRIs+Mood Stabilizer; Patients will be treated with Mood Stabilizer combined with Selective Serotonin Reuptake Inhibitors/ Serotonin and Norepinephrine Reuptake Inhibitors.; Drug: SSRIs/SNRIs+Quetiapine; Patients will be treated with Quetiapine combined with Selective Serotonin Reuptake Inhibitors/ Serotonin and Norepinephrine Reuptake Inhibitors.; Drug: Usual Treatment; Patients' treatment will be decided by the clinical doctor.
No Intervention: BD; the depressive episode of bipolar disorder
No Intervention: HC; healthy control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
remission of acute phase	scored 7 or lower on the Hamilton's Depression Scale with 24 items	12th week
switch rate	the rate of patients who switch from depression to mania or hypomania during 4-year follow-up	4th year

Collaborators and Investigators

• Sponsor: Shanghai Mental Health Center
• Collaborators: Guangzhou Psychiatric Hospital; Shanghai Jiao Tong University School of Medicine; Wuhan Union Hospital, China; Air Force Military Medical University, China; Dalian Seventh People's Hospital
• Investigators: Study Chair: Daihui Peng, MD. PhD., Shanghai Mental Health Center

Study record dates

Study Major Dates

• Study Start (Actual): August 12, 2019
• Primary Completion (Anticipated): October 31, 2022
• Study Completion (Anticipated): October 31, 2022

Study Registration Dates

• First Submitted: December 16, 2019
• First Submitted That Met QC Criteria: December 20, 2019
• First Posted (Actual): December 23, 2019

Study Record Updates

• Last Update Posted (Actual): December 23, 2019
• Last Update Submitted That Met QC Criteria: December 20, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Adrenergic alpha-Agonists; Adrenergic Agonists; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Serotonin Receptor Agonists; Sympathomimetics; Vasoconstrictor Agents; Quetiapine Fumarate; Norepinephrine; Serotonin; Serotonin and Noradrenaline Reuptake Inhibitors; Serotonin Uptake Inhibitors
• Other Study ID Numbers: CRC2018ZD05

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

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