A Standard of Care Study of Patients With Major Depressive Disorder Who Have Had an Inadequate Response to a Selective Serotonin Reuptake/Serotonin-Norepinephrine Reuptake Inhibitor Antidepressant

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety (adverse events, serious adverse events, deaths, suicidality) of participants with major depressive disorder (MDD) treated according to the standard of care (SOC).

Official Title
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A Prospective, Observational Standard of Care Study of Patients With Major Depressive Disorder Who Have Had an Inadequate Response to a Selective Serotonin Reuptake /Serotonin-Norepinephrine Reuptake Inhibitor Antidepressant as a Control Arm for the Safety Assessments in the Seltorexant Phase 3 Program

Conditions
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Depressive Disorder, Major

Intervention / Treatment
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* Other: Standard of Care (SOC)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Has a diagnosis of Major Depressive Disorder (MDD) without psychotic features as confirmed by the Mini International Neuropsychiatric Interview (MINI) Treatment with an selective serotonin reuptake inhibitor (SSRI)/serotonin-norepinephrine reuptake inhibitor (SNRI) for at least 6 weeks at an adequate dose (per Massachusetts General Hospital-Antidepressant Treatment Response Questionnaire [MGH-ATRQ]). Specifically, one of the following in any formulation is allowed: SSRIs: citalopram, duloxetine, escitalopram, fluvoxamine, fluoxetine, milnacipran, levomilnacipran, paroxetine, sertraline; SNRIs: venlafaxine, desvenlafaxine, vilazodone, or vortioxetine In the opinion of the treating clinician, the participant requires augmentation of the current antidepressant treatment and plans to initiate augmentation treatment in the near future. The participant has agreed to receive augmentation treatment Is currently an outpatient receiving psychiatric care (not inpatient care settings) Has a body mass index (BMI) of 18-40 kilograms per meter square (Kg/m^2), inclusive Exclusion Criteria: Taking more than one antidepressant (regardless of class) at therapeutic doses (therapeutic doses per MGH-ATRQ). A second antidepressant is allowed to be taken at a lower dose if for sleep or pain management Is currently taking a benzodiazepine at higher doses than the equivalent of 3 milligrams (mg) of lorazepam Current diagnosis of a psychotic disorder including MDD with psychosis, bipolar disorder, intellectual disability, dementia, autism spectrum disorder, borderline personality disorder, or somatoform disorders Has treatment resistant depression (TRD) as defined by lack of response (less than [<] 25 percent [%] improvement) of 2 or more antidepressants of adequate dose (per MGH-ATRQ) and duration (6 weeks) in this episode Current diagnosis of PTSD, obsessive compulsive disorder, fibromyalgia, anorexia nervosa, or bulimia nervosa. Participants may be enrolled if they have been in remission for the past year

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 74 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| MDD Participants with Insufficient Response to SSRI/SNRI (antidepressant)<br>Major Depressive Disorder (MDD) participants with insufficient response to a selective serotonin reuptake inhibitor (SSRI)/serotonin-norepinephrine reuptake inhibitor (SNRI) (antidepressant) and starting an adjunctive therapy will be observed to create an external control arm (ECA) based on real world data (RWD) from electronic health records (EHR) data during routine medical care (standard of care [SOC]) combined with scheduled research assessments. | Other: Standard of Care (SOC)<br>* Participants will not receive any intervention as a part of this study. Participants will receive SOC treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Spontaneously Reported Adverse Events (AEs) | Number of participants with spontaneously reported AEs will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. | Up to 1 year | 
| Number of Participants with AEs Collected through Generic Assessment of Side Effects (GASE) | Number of participants with AEs collected through GASE will be reported. The GASE is an instrument to assess side effects in clinical studies that allows the detection of drug induced AEs. | Up to 1 year | 
| Number of Participants with Hospitalization for Psychiatric Reasons | Number of participants with hospitalizations for psychiatric reasons will be reported. | Up to 1 year | 
| Number of Participants with Hospitalization for Medical Reasons | Number of participants with hospitalizations for medical reasons will be reported. | Up to 1 year | 
| Number of Participants with Other Serious Adverse Events (SAEs) | SAE is any untoward medical occurrence that at any dose results in any of the following outcomes: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important. | Up to 1 year | 
| Number of Participants with Deaths | Number of participants with deaths will be reported. | Up to 1 year | 
| Number of Participants with Suicide Attempts and Completed Suicides | Number of participants with suicide attempts and completed suicides will be reported. | Up to 1 year | 
| Suicidality Assessment Using the Columbia Suicide Severity Rating Scale (C-SSRS) Score | Suicidality assessment using the C-SSRS will be reported. C-SSRS is semi structured clinician-administered questionnaire designed to solicit the occurrence, severity, and frequency of suicide-related ideation and behaviors. Scale consists of 28 items in 4 sections: suicide behavior, actual attempts, suicidal ideation, and intensity of ideation. Suicidal ideation consists of 5 yes/no items: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intention to act, active suicidal ideation with some intent to act without specific plan, active suicidal ideation with specific plan and intent. Worsening of suicidal ideation will be an increase in severity of suicidal ideation from baseline. | Up to 1 year | 
| Number of Participants with Suicidal Ideation as Assessed by C-SSRS | Number of participants with suicidal ideation as assessed by C-SSRS, particularly codes of 4 or 5 will be reported. C-SSRS is semi structured clinician-administered questionnaire designed to solicit the occurrence, severity, and frequency of suicide-related ideation and behaviors. Scale consists of 28 items in 4 sections: suicide behavior, actual attempts, suicidal ideation, and intensity of ideation. Suicidal ideation consists of 5 yes/no items: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intention to act, active suicidal ideation with some intent to act without specific plan, active suicidal ideation with specific plan and intent. Worsening of suicidal ideation will be an increase in severity of suicidal ideation from baseline. | Up to 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events of Special Interest (AESI) | Number of participants with AESI: Cataplexy, Sleep paralysis, Complex sleep-related behaviors, Falls, Motor vehicle accidents will be reported. | Up to 1 year | 
| Change from Baseline in Weight Over Time | Change from baseline in weight over time will be reported. | Baseline (Week 1) up to 1 year | 
| Percentage of Participants with Clinically Meaningful Change in Weight | Percentage of participants with clinically meaningful change in weight (greater than or equal to [>=] 7 percent [%]) from baseline to end of study will be reported. | Baseline (Week 1) to end of study (up to 1 Year) | 
| Change from Baseline in Hemoglobin Level Over Time | Change from baseline in hemoglobin level over time will be reported. | Baseline (Week 1), Week 26 and Week 52 | 
| Change from Baseline in Platelet and White Blood Cell (WBC) Count Over Time | Change from baseline in platelet and WBC count with differential over time will be reported. | Baseline (Week 1), Week 26 and Week 52 | 
| Change from Baseline in Hematocrit Level Over Time | Change from baseline in hematocrit level over time will be reported. | Baseline (Week 1), Week 26 and Week 52 | 
| Change from Baseline in Red Blood Cell (RBC) Count Over Time | Change from baseline in RBC count over time will be reported. | Baseline (Week 1), Week 26 and Week 52 | 
| Change from Baseline in Sodium, Potassium, Chloride and Bicarbonate Level Over Time | Change from baseline in sodium, potassium, chloride and bicarbonate level over time will be reported. | Baseline (Week 1), Week 26 and Week 52 | 
| Change from Baseline in Blood Urea Nitrogen (BUN), Creatinine, Glucose, Total and Direct Bilirubin, Calcium and Phosphate Level Over Time | Change from baseline in BUN, creatinine, glucose, total and direct bilirubin, calcium and phosphate level over time will be reported. | Baseline (Week 1), Week 26 and Week 52 | 
| Change from Baseline in Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Alkaline Phosphatase Level Over Time | Change from baseline in AST, ALT, alkaline phosphatase level over time will be reported. | Baseline (Week 1), Week 26 and Week 52 | 
| Change from Baseline in Albumin and Total Protein Level Over Time | Change from baseline in albumin and total protein level over time will be reported. | Baseline (Week 1), Week 26 and Week 52 | 
| Change from Baseline in Total Cholesterol, Low-density Lipoprotein Cholesterol, Triglycerides, High-density Lipoprotein Cholesterol Level Over Time | Change from baseline in total cholesterol, low-density lipoprotein cholesterol (calculated), triglycerides, high-density lipoprotein cholesterol level over time will be reported. | Baseline (Week 1), Week 26 and Week 52 |