Inclusion Criteria:  Male and female patients (outpatients) between the regional age of majority (18 or 19 years of age) to 65 years of age, inclusive, at the time of informed consent. Primary diagnosis of MDD and in a current non-psychotic MDE as defined by DSM-5 criteria, who have been outpatients for at least 4 weeks, and have an inadequate response, per investigator judgment, to 1 or 2 adequate treatments of ADTs in their current MDE, including current ADT. Patients with a Patient Health Questionnaire 9-item scale (PHQ-9) ≥ 15 at the screening and baseline visits, if separate.  Exclusion Criteria:  Patients currently or previously treated with brexpiprazole including patients who received brexpiprazole in any prior clinical trial.  Patients with a concurrent DSM-5 diagnosis of the following will be excluded:  Schizophrenia or schizoaffective disorder Bipolar I or bipolar II disorder Post-traumatic stress disorder Dementia Eating disorder Borderline personality disorder Antisocial personality disorder Patients with a suicidality score of 3 based on IDS-SR suicidality item 18 or patients who, in the opinion of the investigator, presents a serious risk of suicide.