Inclusion Criteria:  Male or female patients between the ages of 18 and 65 years, inclusive;  Meets DSM-5 criteria for MDD as confirmed by using the MINI and meets all of the following criteria:  The start of the current major depressive episode (MDE) is at least 8 weeks but not more than 18 months prior to Screening; Has at least moderate severity of illness based on rater-administered MADRS total score ≥ 24 at Screening and at Baseline; Has at least moderate severity of illness based on CGI-S score ≥ 4 at Screening and at Baseline; Has a Quick Inventory of Depressive Symptomatology-Self Report-16 item (QIDS-SR-16) score ≥14 at Screening and at Baseline; and the current MDE is causing clinically significant distress or impairment in social, occupational, or other important areas of functioning.  Currently having an inadequate response to ADT (less than 50% improvement) as confirmed by the Investigator and taking at least the minimum effective dose (per package insert) of one of the following antidepressants as monotherapy treatment for at least 6 weeks duration:  citalopram/escitalopram fluoxetine paroxetine sertraline duloxetine levomilnacipran/milnacipran (if locally approved for MDD) venlafaxine/desvenlafaxine buproprion vilazodone vortioxetine  Exclusion Criteria:  Within the patient's lifetime, has a confirmed DSM-5 psychiatric diagnosis other than MDD, including:  Schizophrenia, Schizoaffective Disorder, Schizophreniform Disorder or other psychotic disorder; Bipolar Disorder;  Within 6 months of Screening, has a confirmed DSM-5 psychiatric diagnosis other than MDD including:  Anxiety disorders such as Panic Disorder or Generalized Anxiety Disorder; Obsessive-compulsive Disorder; Posttraumatic Stress Disorder as primary diagnoses. Eating disorder; Substance use disorders (excluding nicotine); Personality disorder of sufficient severity to have a major impact on the patient's psychiatric status; Within 12 months of Screening, has had any other psychiatric condition (other than MDD) that has been the main focus of treatment; The patient experiences a ≥ 25% decrease in the MADRS total score between Screening and Baseline; The patient experiences a ≥ 25% decrease in the QIDS-SR-16 total score between Screening and Baseline;  In the opinion of the Investigator, the patient has a significant risk for suicidal behavior during participation in the study or:  At Screening, the patient scores "yes" on Suicidal Ideation Items 4 or 5 of the Columbia-Suicide Severity Rating Scale (C-SSRS) within 6 months prior to Screening, or at Baseline, the patient scores "yes" on Suicidal Ideation Items 4 or 5 since the Screening Visit; At Screening, the patient has had 1 or more suicide attempts within 2 years prior to Screening; At Screening or Baseline, the patient scores ≥ 5 on MADRS Item 10 (Suicidal Thoughts), or The patient is considered to be in imminent danger to him/herself or others. The patient has a first MDE at age 60 years or older.