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