A Randomized Trial of Response to Psychopharmacotherapy According to Multimodal Serum Biomarkers in Depression

Study Overview
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Brief Summary
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The primary purpose of this study is to compare the short (12 week) and long-term (1-year) efficacy and the tolerability between stepwise psychopharmacotherapy and antidepressant monotherapy for 12 weeks in adult patients with major depressive disorders, stratified by the multimodal serum biomarker scores.

Detailed Description
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This is prospective randomized controlled trials (RCT) to evaluate clinical impact of antidepressant monotherapy vs stepwise psychopharmacotherapy in patients with major depressive disorders, stratified by multimodal serum biomarker scores. Participants will be predicted treatment response based on the multimodal serum biomarker scores at baseline, will be categorized into good and poor treatment responders and then randomly assigned to two groups: stepwise pharmacotherapy group and antidepressant monotherapy group. The hypothesis is that in the good treatment responder, the depression remission will be achieved irrespective of treatment modality (stepwise pharmacotherapy or antidepressant monotherapy) group while in poor treatment responders, the treatment response of stepwise pharmacotherapy will be superior to those of antidepressant monotherapy.

Official Title
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A Randomized Clinical Trial of Response to Psychopharmacotherapy According to Multimodal Serum Biomarkers in Depressive Patients

Conditions
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Major Depressive Disorder

Intervention / Treatment
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* Drug: stepwise pharamacotherapy
* Drug: antidepressant monotherapy group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 19 to 65 years Diagnostic and Statistical Manual of Mental Disorders-5 criteria for MDD by study psychiatrists Score≥17 on HDRS-17 With ability to understand the objective of the study and sign informed consent Initiation of an antidepressant treatment for the current episode or no psychotropics excluding sleep pills or benzodiazepines within 1 month of participation Exclusion Criteria: Current or lifetime DSM-IV diagnosis of bipolar disorder, schizophrenia, schizoaffective disorder, schizophreniform disorder, psychotic disorder NOS, or other psychotic disorders current major depressive disorder with psychotic features History of organic psychosis, epilepsy, or seizure disorder Current anorexia nervosa or obessive compulsive disorder Unstable or uncontrolled medical condition Unable to complete the psychiatric assessment or comply with the medication regimen due to a severe physical illness History of anticonvulsant treatment Electroconvulsive therapy for the current depressive episode Hospitalization for any psychiatric diagnosis except depressive disorder (e.g., alcohol/drug dependence) severly high risk of suicide, self-harm or homicide by investigator's assessment Pregnant or breastfeeding lack of treatment information on the current depressive episode

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 65 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Good responder group-stepwise pharamacotherapy group<br>Using multimodal serum biomaker scores, patients will be divided into good/poor responder. Then good responder group will be randomized into stepwise pharamacotherapy group vs antidepressant monotherapy(escitalopram) group. In the stepwise pharamacotherapy group, treatment strategies (augmentation with antipsychotics (aripiprazole), augmentation with mood stabilizer (lithium),combination (mirtazapine)) will be determined every 3 weeks. | Drug: stepwise pharamacotherapy<br>* In the stepwise pharamacotherapy group, treatment strategies (augmentation with antipsychotics (aripiprazole), augmentation with mood stabilizer (lithium),combination (mirtazapine)) will be determined every 3 weeks.<br>* Other names: escitalopram with mirtazapine combination;|
| Active Comparator: Good responder group-antidepressant monotherapy group<br>Using multimodal serum biomaker scores, patients will be divided into good/poor responder. Then good responder group will be randomized into stepwise pharamacotherapy group vs antidepressant monotherapy(escitalopram) group. In the antidepressant monotherapy group, dosage escalation will be determined every 3 weeks. | Drug: antidepressant monotherapy group<br>* In the antidepressant monotherapy group, dosage escalation will be determined every 3 weeks.<br>* Other names: escitalopram monotherapy;|
| Experimental: Poor responder group-stepwise pharamacotherapy group<br>Using multimodal serum biomaker scores, patients will be divided into good/poor responder. Then poor responder group will be randomized into stepwise pharamacotherapy group vs antidepressant monotherapy(escitalopram) group. In the stepwise pharamacotherapy group, treatment strategies (augmentation with antipsychotics (aripiprazole), augmentation with mood stabilizer (lithium),combination (mirtazapine)) will be determined every 3 weeks. | Drug: stepwise pharamacotherapy<br>* In the stepwise pharamacotherapy group, treatment strategies (augmentation with antipsychotics (aripiprazole), augmentation with mood stabilizer (lithium),combination (mirtazapine)) will be determined every 3 weeks.<br>* Other names: escitalopram with mirtazapine combination;|
| Active Comparator: Poor responder group-antidepressant monotherapy group<br>Using multimodal serum biomaker scores, patients will be divided into good/poor responder. Then poor responder group will be randomized into stepwise pharamacotherapy group vs antidepressant monotherapy(escitalopram) group. In the antidepressant monotherapy group, dosage escalation will be determined every 3 weeks. | Drug: antidepressant monotherapy group<br>* In the antidepressant monotherapy group, dosage escalation will be determined every 3 weeks.<br>* Other names: escitalopram monotherapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Remission and treatment response status by Hamilton Depression Rating Scale (HRDS) ≤7 | Remission defined by Hamilton Depression Rating Scale (HRDS) ≤7 and treatment response defined as ≥50% decrease in the baseline HAMD total score after stepwise psychopharmacotherapy or antidepressant monotherapy | From baseline to 12 week, 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The changes of Hamilton Rating Scale for Depression (HAMD) total score | To measure the change of the severity of depressive symptoms using observer rating scale after stepwise psychopharmacotherapy or antidepressant monotherapy | From baseline to 12 week, 1 year | 
| The changes of Hospital Anxiety and Depression Scale (HADS) total score, depression subscore, anxiety subscore | To measure the change of the severity of depressive symptoms using self-reported scale after stepwise psychopharmacotherapy or antidepressant monotherapy | From baseline to 12 week, 1 year | 
| The changes of Clinical Global Impression (CGI)-severity and improvement score | To measure the change of the global severity and improvement of depressive symptoms after stepwise psychopharmacotherapy or antidepressant monotherapy | From baseline to 12 week, 1 year | 
| The changes of Brief Psychiatric Rating Scale(BPRS) suicide item score | To measure the change of the suicidal-related severity after stepwise psychopharmacotherapy or antidepressant monotherapy | From baseline to 12 week, 1 year | 
| The changes of Sheehan Disability Scale score | To measure the change of the functional disability after stepwise psychopharmacotherapy or antidepressant monotherapy | From baseline to 12 week, 1 year | 
| The changes of EuroQol-5D score | To measure the change of quality of life status after stepwise psychopharmacotherapy or antidepressant monotherapy | From baseline to 12 week, 1 year | 
| The changes of Social and Occupational Functioning Assessment Scale score | To measure the change of the social and occupational function after stepwise psychopharmacotherapy or antidepressant monotherapy | From baseline to 12 week | 
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) in the Treatment Period | An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An adverse event can therefore be any unfavorable and unintended sign (i.e. laboratory value), symptom, or disease temporally associated with the use of a medicinal product, whether or not related to the medicinal product. A TEAE is an AE that occurs or worsens after receiving study drug | First dose of study drug to last dose of study drug in the 26-week Treatment Period and 1 year after baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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depression, antidepressant monotherapy, stepwise psychopharmacotherapy, multimodal serum biomarker score