Study to Evaluate the Efficacy, Safety and Tolerability of an Oral Aripiprazole/Escitalopram Combination Therapy in Patients With Major Depressive Disorder (MDD) (ACES 255)

This will be a multicenter, randomized, double-blind study designed to assess the efficacy, safety and tolerability of an oral Aripiprazole/Escitalopram combination therapy in subjects with MDD who have demonstrated an incomplete response to a prospective trial of Escitalopram, and report a treatment history for the current MDD episode of an inadequate response to at least one and no more than three adequate trials of an approved antidepressant other than Escitalopram. An inadequate response is defined as less than a 50% reduction in depressive symptom severity as assessed by the subject's self-report on the Massachusetts General Hospital Antidepressant Treatment Response Questionnaire (ATRQ) and evaluated by the investigator as part of the subject's medical and psychiatric history. An adequate trial is defined as an antidepressant treatment for at least 6 weeks duration (or at least 3 weeks for combination treatments) at an approved dose as specified in the ATRQ.

The study will be organized as follows:

• Screening Phase
• Single-blind Prospective Treatment Phase
• Single-blind Continuation Phase (Responder) or Double-blind Randomization Phase (non-Responder)
• 30 day Post Treatment Follow-up

Assigned Interventions:

• Escitalopram monotherapy
• Aripiprazole/Escitalopram combination therapy
• Aripiprazole monotherapy

• Drug: Escitalopram
  Escitalopram monotherapy
• Drug: Aripiprazole
  Aripiprazole monotherapy
• Drug: Aripiprazole/Escitalopram combination
  Aripiprazole/Escitalopram combination therapy

• Active Comparator: Escitalopram monotherapy
  Intervention: Drug: Escitalopram
• Active Comparator: Aripiprazole monotherapy
  Intervention: Drug: Aripiprazole
• Active Comparator: Aripiprazole/Escitalopram combination therapy
  Intervention: Drug: Aripiprazole/Escitalopram combination

Inclusion Criteria:

• Subjects with a current diagnosis of a major depressive episode. The current depressive episode must be ≥ 8 weeks in duration
• Subjects willing to discontinue all prohibited psychotropic medication starting from the time of signing the informed consent and during the study period
• Subjects with a HAM-D17 Total Score ≥ 18 at the Baseline Visit for the Prospective Treatment Phase

Exclusion Criteria:

• Lack of prior treatment with an antidepressant during the current depressive episode
• Subjects who report treatment with adjunctive or monotherapy antipsychotic treatment during the current depressive episode.
• Subjects experiencing hallucinations, delusions or any psychotic symptomatology in the current depressive episode
• Subjects with epilepsy or significant history of seizure disorders
• Subjects with a clinically significant current diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal or histrionic personality disorder
• Subjects who have received electroconvulsive therapy (ECT) in the last 10 years