Brexpiprazole as Adjunctive Therapy With Major Depressive Disorder and an Inadequate Response to Previous Adjunctive Therapy

Inclusion Criteria: * Clinical diagnosis of MDD * In current major depressive episode of ≥ 8 weeks in duration and includes an inadequate response to at least 1 adjunctive treatment. * Positive history of at least 1 additional failure to an adequate monotherapy antidepressant treatment. * HAM-D17 total score≥ 18 * Currently receiving SSRI of SNRI with adjunctive treatment for at least 6 weeks before screening. * Willing to discontinue use of all prohibited psychotropic medications * Historical positive serological results for HIV, hepatitis B/C * Able to provide written informed consent prior to the initiation of any protocol-required procedures * Subjects who could potentially benefit from adjunctive treatment with Brexpiprazole Exclusion Criteria: * Sexually active women of childbearing potential * Male subjects not practicing 2 different methods of birth control * Females who are breastfeeding and/or who have a positive pregnancy test result * Subjects who have received ECT for the current major depressive episode. * Subjects who have had an inadequate response to ECT * Current need for involuntary commitment or who have been hospitalized within 4 weeks of screening * Current Axis I (DSM-IV-TR) * Current Axis II (DSM-IV-TR) * Subjects experiencing hallucinations, delusions, or any psychotic symptomatology in the current major depressive episode. * Subjects receiving new onset psychotherapy. * Subjects who answer "Yes" on the C-SSRS Suicidal Ideation Item 4, Item 5, or on any of the 5 C-SSRS Suicidal Behavior Items * Subjects who have met DSM-IV-TR criteria for substance abuse or dependence within the past 180 days * Hypothyroidism or hyperthyroidism * Clinically significant neurological, hepatic, renal, metabolic, haematological, immunological, cardiovascular, pulmonary, or gastrointestinal disorders * Currently treated with insulin for diabetes * Uncontrolled hypertension or symptomatic hypotension, or orthostatic hypotension * Known ischemic heart disease or history of myocardial infarction, congestive heart failure, angioplasty, stenting, or coronary artery bypass surgery * Epilepsy or history of seizures * Positive drug screen * The following laboratory test and ECG results are exclusionary: 1. Platelets ≤ 75,000/mm3 2. Hemoglobin ≤ 9 g/dL 3. Neutrophils, absolute ≤ 1000/mm3 4. AST \> 2 × ULN 5. ALT \> 2 × ULN 6. CPK \> 3 × ULN, unless discussed with and approved by the medical monitor 7. Creatinine ≥ 2 mg/dL 8. HbA1c ≥ 7.0% 9. Abnormal free T4 (Note: Free T4 is measured only if result for TSH is abnormal.) 10. QTcF ≥ 470 msec for females and ≥ 450 msec for males * Treatment with an MAOI or EMSAM within 14 days of the Baseline visit. * Use of benzodiazepines and/or hypnotics within 7 days prior to the first dose of IMP * Use of oral neuroleptics within 7 days prior or long-acting approved atypical antipsychotics ≤ 1 full cycle plus ½ cycle prior to the first dose of IMP * Subjects who would be likely to require prohibited concomitant therapy during the trial. * Subjects who previously participated in any prior brexpiprazole trial * History of neuroleptic malignant syndrome or serotonin syndrome * History of true allergic response to more than one class of medications * Prisoners or subjects who are compulsorily detained for treatment of either a psychiatric or physical illness. * Subjects who participated in a clinical trial within the last 180 days or who participated in more than 2 clinical trials within the past year. * Any subject who, in the opinion of the investigator or medical monitor, should not participate.