A Study to Evaluate ALKS 5461 in Subjects With Major Depressive Disorder (MDD)

The study will measure efficacy using the HAM-D-17, the MADRS, and the CGI-S as well as
using other scales and assessments.

Inclusion Criteria:

- Diagnosed with a major depressive episode (MDE)

- Body mass index less than or equal to 40 kg/m2

- Have been treated with an adequate dose of SSRI/SNRI during the current MDE for at
least 8 weeks, with the same, adequate dose over the last 4 weeks that is expected to
remain stable throughout the study

- History of inadequate response during the entire current MDE to 1 or 2 adequate
antidepressant treatments, including current treatment

- Be otherwise physically healthy

Exclusion Criteria:

- Have an axis I diagnosis of delirium, dementia, amnestic or other cognitive disorder,
schizophrenia or other psychotic disorder, bipolar I or II disorder, eating disorder,
obsessive-compulsive disorder, panic disorder, acute stress disorder, or
posttraumatic stress disorder

- Have a clinically significant current axis II diagnosis of borderline, antisocial,
paranoid, schizoid, schizotypal, or histrionic personality disorder

- Are experiencing hallucinations, delusions, or any psychotic symptomatology in the
current MDE

- Receive new onset psychotherapy within 6 weeks of screening

- Use of opioid agonists (eg, codeine, oxycodone, morphine) within 14 days before
screening

- Have received electroconvulsive therapy during the current MDE

- Have attempted suicide within the past 2 years

- Have a thyroid pathology

- Have a history of a seizure disorder or of neuroleptic malignant syndrome/serotonin
syndrome

- Have a positive test for human immunodeficiency virus (HIV)

Additional inclusion/exclusion criteria may apply