The purpose of this 14 week, randomized, double-blind, placebo controlled study is to assess the safety and efficacy of brexipiprazole to placebo as adjunctive treatment to an assigned open-label marketed antidepressant therapy (ADT) in patients with Major Depressive Disorder.

Inclusion Criteria:

• Outpatients, or inpatients at the time of informed consent whose treatment status can be successfully shifted to outpatient status before enrollment in the antidepressant treatment period
• Male and female patients ≥ 20 to < 65 years of age (at the time of informed consent)
• Patients who have a level of comprehension sufficient to allow them to give written informed consent to all of the observation/examination/evaluation items specified in the protocol, and who can understand the contents of the trial
• Patients with a DSM-5 classification-based diagnosis of "major depressive disorder, single episode" or "major depressive disorder, recurrent episode," and whose current episode has persisted for at least 8 weeks

Exclusion Criteria:

• Women who are pregnant or breastfeeding or who have positive pregnancy test (urine) results at screening
• Sexually active male subjects or sexually active female subjects of childbearing potential, who will not agree to practice 2 different methods of birth control or to remain abstinent during the trial and for 30 days after the final

IMP administration. For birth control, 2 of the following methods must be used:

vasectomy, tubal ligation, vaginal diaphragm, intra-uterine contraceptive device (IUD), oral contraceptives, or condom with spermicide.

• Patients with a treatment history showing that all antidepressants (including those not used for the current major depressive episode) cannot be tolerated

• Patients with a history of electroconvulsive therapy

• Patients with a diagnosis of any of the following diseases according to DSM-5

  1. Neurocognitive disorders
  2. Schizophrenia spectrum and other psychotic disorders
  3. Bipolar and related disorders
  4. Feeding and eating disorders
  5. Obsessive-compulsive disorder
  6. Panic disorder
  7. Posttraumatic stress disorder

Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal.

Data will be available after marketing approval in global markets, or beginning 1-3 years following article Publication. There is no end date to the availability of the data.

Otsuka will share data on an Otsuka-owned remotely accessible data sharing platform with Python and R analytical software. Research requests should be directed to clinicaltransparency@Otsuka-us.com.

Full Analysis Set (FAS) which comprised subjects who, after randomization, had received at least 1 dose of the study medication in the double-blind period (Phase B), and from whose the Montgomery Åsberg Depression Rating Scale (MADRS) total scores had been obtained at baseline and at least 1 time point after initiation of the treatment.

Adverse events were monitored from signing of the informed consent form until post-treatment observation period for up to 30 days (±5 days) after the final day of study medication administration (end of trial date [final day of observation]).

Subjects who received at least one dose of IMP were included in the safety analysis.