This study will evaluate the efficacy and safety of ALKS 5461.

Inclusion Criteria:

• Have a Body Mass Index (BMI) of 18.0 to 40.0 kg/m2, inclusive
• Agree to use an acceptable method of contraception for the duration of the study
• Have a Major Depressive Disorder (MDD) primary diagnosis
• Have no more than 2 inadequate responses to antidepressant therapy (ADT) in the current Major Depressive Episode (MDE)
• Additional criteria may apply

Exclusion Criteria:

• Have a current primary Axis-I disorder other than MDD
• Have used opioid agonists (eg, codeine, oxycodone, tramadol, morphine) or opioid antagonists (eg, naloxone, naltrexone) within 14 days
• Have received electroconvulsive therapy treatment within the last 2 years or received more than one course of electroconvulsive treatment during lifetime
• Have attempted suicide within the past 2 years
• Have a positive test for drugs of abuse
• Are pregnant, planning to become pregnant, or breastfeeding
• Have a history of intolerance, allergy, or hypersensitivity to buprenorphine or opioid antagonists (eg, naltrexone, naloxone)
• Have had a significant blood loss or blood donation within 60 days
• Additional criteria may apply

Should an Investigator desire to disclose study results, Sponsor will review the results disclosure prior to public release and can embargo the disclosure for a period of at least 60 days. Revisions to the disclosure will be negotiated in good faith. For a multicenter study the Investigators agree to publish/publicly present the results together with the other sites for the 12 month period after study results are available unless Sponsor grants written permission in advance.