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): 18.0-64.0,  Depressive Disorder, Major Body mass index (BMI) must be between 18 and 32 kilogram per square meter (kg/m^2) inclusive Related to symptoms of depression: Participant must meet the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV or V diagnostic for Major Depressive Disorder [MDD] (International Classification of Diseases (ICD)-code F32.x and F33.x), without psychotic features, as confirmed by the MINI 6.0; participant must have an IDS-C30 total score greater than or equal to (>=) 30 using the semi-structured interview guide for the IDS-C30 Participant is, during this episode of depression, treatment naïve OR treated with at most one Selective serotonin reuptake inhibitor (SSRI) over a minimum of 6 weeks and a maximum of 6 months, and subject is being treated at an adequate dose, showing a partial response at enrolment A woman of childbearing potential must have a negative serum pregnancy test at screening and a negative urine pregnancy test upon admission 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 a primary DSM-IV or V diagnosis of general anxiety disorder (GAD), panic disorder, obsessive compulsive disorder, posttraumatic stress disorder, anorexia nervosa, or bulimia nervosa. Participants with comorbid GAD, social anxiety disorder, or panic disorder for whom MDD is considered the primary diagnosis are not excluded Has a length of current major depressive episode greater than (>) 24 months despite adequate treatment Has failed more than 2 treatments with a different pharmacological mode of action despite an adequate dose and duration during a previous, or the current depressive episode Participant has a history of substance use disorder according to DSM-V except nicotine or caffeine, within 6 months before Screening. However, participants who have completed a treatment for (alcohol) addiction more than 8 weeks prior to first dose administration and are under continuous control of the study center, may be included if the risk to fall back is considered minimal and no significant abnormalities are shown in clinical laboratory or other predose safety assessments Obstructive sleep apnea/hypopnea (apnea/hypopnea index >10) or restless legs syndrome (periodic leg movements with arousal index >15) as assessed on the first or second polysomnography (PSG) recording during screening