Patient description: A 46-year-old Asian woman with MDD complains of persistent feelings of sadness and loss of interest in daily activities. She states that her mood is still depressed most of the days. She complains of loss of energy and feelings of worthlessness nearly every day. She is on anti-depressants for the past 6 months, but the symptoms are still present. She does not drink alcohol or smoke. She used to exercise every day for at least 30 min., but she doesn't have enough energy to do so for the past 3 weeks. She also has some digestive issues recently. She is married and has 4 children. She is menopausal. Her husband was diagnosed with colon cancer a year ago and is undergoing chemotherapy. Her past medical history is unremarkable. Her family history is negative for any psychologic problems. Her HAM-D score is 20.

Clinical trial eligibility criteria: eligible ages (years): 18.0-75.0,  Major Depressive Disorder Coronary Artery Disease DSM-5 diagnosis of a major depressive disorder based on clinical evaluation by the study psychiatrist 2. At least moderate severity of depression as indicated by a Montgomery-Asberg Depression Rating Scale (MADRS) score of 22 or greater 3. History of coronary artery disease as defined by History of coronary stenosis in one or more vessels that is greater ≥ 70% by coronary angiography or CT angiogram, OR History of abnormal stress test (at least medium-sized, moderate, reversible defect), OR History of documented myocardial infarction including ST elevation myocardial infarction or non-ST elevation myocardial infarction (with elevated troponins), OR 4. Evidence of adequate treatment of the coronary artery disease as defined by at least one of the following that was done at least six months prior to the Screening visit, AND was followed by the patient being clinically stable in the opinion of a cardiologist who has evaluated the case Coronary artery bypass grafting (CABG) Percutaneous coronary intervention (PCI)/ stenting Adequate management with optimal medical treatment (such as one or more of the following medications: aspirin, beta blockers, a statin (e.g., atorvastatin), and either an ACE inhibitor or an angiotensin-receptor blocker.) Key  Psychiatric Patients who in the past have failed to respond to a trial of vortioxetine at the minimum recommended dose (10 mg/day) or greater taken for at least six weeks, or had unacceptable adverse effects while taking vortioxetine. 2. Patients must not have failed treatment with more than one antidepressant (taken at an adequate dose and for at least six weeks) in the current episode of major depressive disorder (i.e., did not have > 50% reduction in severity of depression based on patient history) 3. Patients with a current primary DSM-5 diagnosis of: i) Delirium, dementia, amnestic, or other cognitive disorder; ii) Eating Disorder (including Anorexia Nervosa or Bulimia); iii) Obsessive Compulsive Disorder; iv) Panic Disorder; v) Post-Traumatic Stress Disorder (PTSD); 4. Current or past (lifetime) DSM-5 diagnosis of: i) Bipolar I or II disorder; ii) Hypomanic episode iii) Substance-induced manic or hypomanic episode iii) Schizophrenia or other psychotic disorder Cardiovascular Patients who have had a myocardial infarction within 30 days of the screening visit 2. Any cardiovascular condition that is unstable or decompensated 3. In the opinion of the Investigators, the patient is at significant risk of cardiovascular adverse events 4. Coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI)/ stenting within three months of the screening visit 5. Admission to a hospital for any cardiac condition within three months of the screening visit 6. Decompensated heart failure within 6 months of the screening visit 7. QTc prolongation (screening ECG with QTc ≥ 450 msec for men or QTc ≥ 470 msec for women) using QTc Fridericia correction 8. Second-degree (if Mobitz II) or third-degree atrioventricular block 9. Heart rate on ECG of ≤ 50 bpm or ≥ 120 bpm or any heart rate that is clinically symptomatic 10. Premature Ventricular Contractions (PVCs) associated with clinical symptoms and/or any complex premature ventricular contractions (ie, PVCs that are frequent [> 30/hr] or ≥ 2 beats if multifocal, or show bigeminy, trigeminy, quadrigeminy, couplets, triplets [salvos], or the R on T phenomenon) 11. Atrial fibrillation or flutter 12. Supine (after patient has been supine for 5 minutes) systolic BP > 160 mm Hg or < 90 mm Hg or diastolic BP > 100 mm Hg or any systolic or diastolic BP that is symptomatic or clinically significant based on the opinion of the Principal Investigator 13. Patients who are receiving warfarin