Study of Brexpiprazole as Adjunctive Treatment of Irritability in Patients With Major Depressive Disorder and an Inadequate Response to Antidepressant Therapy

Inclusion Criteria:

Main selection criteria at screening visit:

- The patient has a Major Depressive Episode (MDE) associated to Major Depressive
Disorder (MDD) diagnosed according to Diagnostic and Statistical Manual of Mental
Disorders, 4th edition, Text Revision (DSM-IV-TR™). The current MDE should be
confirmed using the Mini International Neuropsychiatric Interview (MINI)

- The patient has an inadequate response to at least one antidepressant treatment
(including the treatment the patient is taking at screening) in the current MDE, as
documented by self-report as less than a pre-defined percentage response on the
Massachusetts General Hospital Antidepressant Treatment Response Questionnaire
(ATRQ).

- Pre-defined MADRS total score

- Pre-defined CGI-S total score

- The patient has had the current MDE for ≥10 weeks

- The patient is receiving a SSRI or SNRI antidepressant treatment for ≥6 weeks, at
same dosage for ≥2 weeks

- Pre-defined Inventory of Depressive Symptomatology - Clinician-Rated - 30 items
(IDS-C 30) Item 6 Mood (irritable) score

Main inclusion criteria at baseline visit:

- The patient still fulfils DSM-IV-TR™ criteria for MDE

- Pre-defined MADRS total score

- Pre-defined CGI-I (Lead-in period) score

- The patient received the same SSRI or SNRI antidepressant treatment at adequate doses
during the entire lead-in period

- The patient has less than a pre-defined percentage decrease in MADRS score at the end
of the lead-in period as compared to the screening visit

- The patient still has the pre-defined IDS-C 30 Item 6 Mood (Irritable) score

Exclusion Criteria:

- The patient has any current psychiatric disorder or Axis I disorder (DSM-IV-TR™
criteria), established as the principal diagnosis, other than MDD. All anxiety
disorders, impulse-control disorders such as intermittent explosive disorder, as well
as non-suicidal self-injury are not excluded diagnoses as far as they are not
considered as principal diagnosis.

- The patient has a current Axis II (DSM-IV-TR™) diagnosis of antisocial, borderline,
paranoid, schizoid, schizotypical, or histrionic personality disorder.

- The patient has experienced/experiences hallucinations, delusions, or any psychotic
symptomatology in the current MDE.

- The patient, in the opinion of the investigator or based on C-SSRS rating, is at
significant risk of suicide.

- The patient has started formal cognitive or behavioural therapy or systematic
psychotherapy within 6 weeks prior to screening, or plans to start such therapy
during the study. Any ongoing formal psychotherapy initiated more than 6 weeks prior
to screening should be continued with the same methodology and at the same frequency
and intensity during the entire study.

- The patient has a current diagnosis or history of substance abuse or dependence
(excluding nicotine or caffeine) or alcohol abuse or dependence (DSM-IV-TR™ criteria)
<6 months prior to the Screening Visit.

- The patient reports adjunctive treatment with an antipsychotic medication together
with an antidepressant for 3 weeks or more during the current MDE.

- The patient has received electroconvulsive therapy (ECT) <6 months prior to the
Screening Visit or at any time during the current MDE (if its duration is longer than
6 months).

- The patient has had vagus nerve stimulation or a deep brain stimulation device
implanted for the management of depression.

Other inclusion and exclusion criteria may apply.