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,  Major Depressive Disorder Patients must be able to give informed consent, (as required by IRB/IEC), prior to the initiation of any protocol required procedures Patients must be able to understand the nature of the study, agree to comply with the prescribed dosage regimens, report for regularly scheduled office visits, and communicate to study personnel about adverse events and concomitant medication use Patients with a diagnosis of major depressive episode as defined by DSM-IV-TR based on the SCID-CT29; their major depressive episode must be deemed "valid" using the SAFER interview24 administered by remote, independent raters Patients who have reported a history for the current depressive episode of an inadequate response to 1 and no more than 1 adequate SSRI or SNRI treatment. An inadequate response is defined as less than a 50% reduction in depressive symptom severity, as assessed by the MGH ATRQ administered by remote, independent raters. An adequate trial is defined as an antidepressant treatment for at least 8 weeks duration at least at the minimum dose as specified in the MGH ATRQ Patients must have a 17-item Hamilton Rating Scale for Depression (HAM-D-17) (whose score is derived from the HAM-D-28)20 score ≥ 18 during the screening phase to qualify for inclusion. The HAM-D-28 will be administered by the study clinicians at the screening and baseline visits, and by remote, independent raters during the screening phase at the time of the SAFER interview Patients must have a Body Mass Index (BMI) of approximately 18-40 Patients must be able to be reliably rated on the psychiatric scales required by the protocol based on Investigator's judgment Patients must be able to understand and read English Placebo non-responders are defined as those patients who failed to achieve at least a 50% decrease in their MADRS score at visit 8 (Week 6), AND have a MADRS score of = or > 16 at visit 8 (Week 6) Men and women, ages 18 to 65 inclusive  WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period [and for up to 4 weeks after the last dose of investigational product WOCBP using a prohibited contraceptive method that does not meet established and acceptable medical standards Women who are pregnant or breastfeeding Women with a positive pregnancy test on enrollment or prior to investigational product administration Sexually active fertile men not using effective birth control if their partners are WOCBP Patients who do not report any prior inadequate response (equal or greater than 50% decrease in depressive symptom severity) or report an inadequate response (less than 50% decrease in depressive symptom severity) to more than 1 prior adequate trials of antidepressant treatments during the current depressive episode (including monotherapy treatment and distinct combination regimens) at a therapeutic dose (as defined by the MGH ATRQ)22-23 and for an adequate duration (minimum 6 weeks for any monotherapy) Patients who report treatment with adjunctive medication (buspirone, atypical antipsychotics, lithium) to their antidepressant therapy for a minimum of 4 weeks during the current depressive episode Patients with a current need for involuntary commitment or who have been hospitalized within 4 weeks of the Screening Visit for the current major depressive episode Subjects with other DSM-IV-TR Axis I disorders other than Generalized Anxiety Disorder (GAD: 300.02), Social Anxiety Disorder (300.23), or Specific Phobia (300.29). Subjects with co-morbid GAD, Social Anxiety Disorder, or Specific Phobia are ineligible if the co-morbid condition is clinically unstable, requires treatment, or has been the primary focus of treatment within the 6 month period prior to screening. More specifically, patients who have a current Axis I diagnosis Patients experiencing hallucinations, delusions, or any psychotic symptomatology in the current or any previous depressive episode