Brexpiprazole (OPC 34712) Trial in the Treatment of Adults With Major Depressive Disorder and Irritability

* Inclusion Criteria: * Are 18 to 55 years of age, inclusive, at the time of informed consent with a diagnosis of a single or recurrent, nonpsychotic episode of MDD as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR™) and confirmed by the Mini International Neuropsychiatric Interview (M.I.N.I.) and an adequate clinical psychiatric evaluation * Have received a single, trial-approved SSRI or SNRI at an adequate dose for ≥ 6 weeks prior to screening * Have a treatment history of inadequate ADT response to at least one ADT (but not \> 3) for the current episode. The current major depressive episode must be ≥ 6 weeks in duration. (An inadequate ADT response is defined as \< 50% reduction in depressive symptom severity, as measured by subject self-report on the MGH-ATRQ.) * To be eligible for this trial * Have a MADRS Total Score of 20 or more at screening and the Phase A baseline, and have a MADRS Total Score of 18 or more at the Phase B baseline * Have no more than 20% improvement in MADRS Total Score at Phase B baseline compared to Phase A baseline * Have a score of 6 or more on the KSQ based on the Well being and Reversal Distress Anger-hostility subscales at screening, Phase A baseline, and Phase B baseline * Have anger attacks as documented by the AAQ at screening, Phase A baseline, and Phase B baseline * Are right-handed (defined according to the Edinburgh Handedness Inventory) and have normal hearing and normal/corrected-to-normal vision * Are willing to discontinue all prohibited psychotropic medications to meet protocol-required washouts prior to and during the trial period * Eligibility confirmed through a telephone SAFER interview with the subject and an independent expert centralized rater * Exclusion Criteria: * Have a current need for involuntary commitment or have been hospitalized within 4 weeks of screening for the current major depressive episode * Have a current DSM-IV-TR Axis I diagnosis of any of the following: delirium, dementia, amnestic, or other cognitive disorders; schizophrenia, schizoaffective disorder, or other psychotic disorders; bipolar I disorder, bipolar II disorder, or bipolar disorder not otherwise specified; eating disorders (including anorexia nervosa or bulimia); obsessive compulsive disorder; panic disorder; or post-traumatic stress disorder * Have any of the following current Axis II DSM-IV-TR diagnoses: borderline, antisocial, paranoid, schizoid, schizotypal or histrionic personality disorders, or mental retardation * Experiencing hallucinations, delusions, or any psychotic symptomatology in the current major depressive episode