Patient description: The patient is a 47-year-old Asian woman complaining of persistent feelings of sadness. She lost interest in activities she used to enjoy. She states that her mood is mostly depressed for the past 3 weeks. She also lost her appetite , which led to about 5kg weight loss. She complains of loss of energy and feelings of worthlessness nearly every day. She is not using any drugs and she does not smoke. She doesn't drink alcohol. 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 recently diagnosed with colon cancer and he is starting his chemotherapy. There is nothing remarkable in her past medical history and her drug history is only positive for Vit D3 1000 units daily. Her family history is negative for any psychologic problems. Her HAM-D score is 20.

Clinical trial eligibility criteria: eligible ages (years): 18.0-55.0,  Depressive Disorder, Major Have a body mass index (BMI) between 18 and 35 kilogram per meter square (kg/m^2) inclusive (BMI = weight/height^2) Participants must be medically stable based on clinical laboratory tests, medical history, vital signs, and 12-lead electrocardiogram (ECG) performed at screening and baseline Population specific: Participant must meet Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5) diagnostic for MDD (international classification of diseases [ICD]-code F32.x and F33.x), without psychotic features, and confirmed by the Mini International Neuropsychiatric Interview (MINI) 7.0; have a Montgomery Asberg Depression Rating Scale (MADRS) total score greater than or equal to (>=) 25 at screening and must not demonstrate a clinically significant change (that is, an improvement of greater than (>) 20 percent (%) on their MADRS total score) from the screening to the second completion of MADRS by telephone at most 4 days before the baseline visit; Not currently receiving antidepressant drug therapy for >= 2 weeks before screening Men who are sexually active with a women of childbearing potential (WOCBP) and have not had a vasectomy must agree to use a barrier method of birth control A woman of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test before the first dose A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for at least 3 months after receiving the last dose of study drug  Has failed more than 2 treatments (no more than 20 percent (%) response) with a differing pharmacological mode of action despite an adequate dose and duration during a previous, or the current depressive episode Has a diagnosis of Cushing's Disease, Addison's Disease, primary amenorrhea, or other evidence of significant medical disorders of the Hypothalamus pituitary adrenal (HPA) axis Is pregnant or breast feeding Participant has received an investigational drug (including investigational vaccines) or used an invasive investigational medical device within 60 days before the planned first dose of study drug, or has participated in 2 or more interventional clinical studies in the previous 1 year, or is currently enrolled in an interventional study Participant is a man who plans to father a child while enrolled in this study or within 3 months after the last dose of study drug Participant has a history of hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-HCV) positive, or other clinically active liver disease, or tests positive for HBsAg or anti-HCV at screening