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): 18.0-65.0,  Depressive Disorder, Major --Established diagnosis of Major Depressive Disorder (MDD), single episode or recurrent, as confirmed at the time of screening by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 5th version (DSM-5) (SCID-5), with a duration of current depressive episode ≥ 8 weeks and ≤ 12 months at the time of screening visit Montgomery-Åsberg Depression Rating Scale (MADRS) total score ≥ 26 at screening, as confirmed by a trained site based rater AND interactive, computer administered MADRS. The difference in the rater and computer administered MADRS must not exceed more than 7 points (for details refer to section 6.2). In addition, trial participants must have a score of ≥ 3 on the Reported Sadness Item on both MADRS scales (computer administered and rater-administered MADRS) A documented ongoing monotherapy treatment of ≥ 8 weeks at the screening visit, with a protocol specified Selective Serotonin Reuptake Inhibitor (SSRI) or Serotonin Norepinephrine Reuptake Inhibitor (SNRI) (refer to the ISF) at adequate dose (at least minimum effective dose as per prescribing information and as confirmed per detectable drug levels in the screening blood sampling) Male and female participants, 18 to 65 years of age, both inclusively at the time of consent Women who are of child-bearing potential (WOCBP)1 must be able and willing to use two methods of contraception which one highly effective method of birth control per ICH M3 (R2) that result in a low failure rate of less than 1%, plus one additional barrier Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial Able to communicate well, and to understand and comply with trial requirements  Per DSM-5, had ever met diagnostic for schizophrenia, schizoaffective disorder, schizophreniform disorder, bipolar disorder, delusional disorder or MDD with psychotic features as assessed by the Structured Clinical Interview for DSM-5 Clinical Trials (SCID-5) at the time of screening Diagnosis of any other mental disorder (in addition to those as described in Criterion #1) that was the primary focus of treatment within 6 months prior to screening or at baseline (as per clinical discretion of the investigator) Diagnosis with antisocial, paranoid, schizoid or schizotypal personality disorder as per DSM-5 at the time of screening visit. Any other personality disorder at screening visit that significantly affects current psychiatric status and likely to impact trial participation, as per the judgement of investigator Diagnosis of a substance related disorder within 3 months prior to screening visit (with exception of caffeine and tobacco) History of seizure disorders, stroke, brain tumor or any other major neurological illness that can impact participation in the trial History of more than 2 unsuccessful monotherapy treatments (at adequate dosage and duration, per local prescribing information of the product) with an approved antidepressant medication for the current ongoing major depressive episode. These ongoing monotherapy treatment with a protocol specified SSRI or SNRI as described in Criterion #3 Any suicidal behavior in the past 12 months prior to screening (per investigator judgement including an actual attempt, interrupted attempt, aborted attempt, or preparatory acts or behaviour) Any suicidal ideation of type 4 or 5 in the Columbia Suicide Severity Rating Scale (CSSRS) in the past 3 months prior to screening or at screening or baseline visit (i.e. active suicidal thought with method and intent but without specific plan, or active suicidal thought with method, intent and plan)