A Study of ALKS 5461 for Treatment Refractory Major Depressive Disorder (MDD)

Inclusion Criteria: * Have a Major Depressive Disorder (MDD) primary diagnosis * Have a body mass index (BMI) of 18.0 to \</= 40.0 kg/m\^2 * Be willing and able to follow the study procedures and visits as outlined in the protocol (including agreeing not to enroll in any other clinical trials) * Have inadequate responses to antidepressant therapy (ADT) in the current Major Depressive Episode (MDE) * Additional criteria may apply Exclusion Criteria: * Has any finding that would compromise the safety of the subject or affect their ability to adhere to the protocol visit schedule or fulfill visit requirements * Has any other significant medical condition (eg, neurological, psychiatric, or metabolic) or clinical symptom that could unduly risk the subject or affect the interpretation of study data * Has any current primary diagnosis other than MDD, where primary diagnosis is defined as the primary source of current distress and functional impairment * Has experienced hallucinations, delusions, or any psychotic symptoms in the current MDE * Has been hospitalized for MDD within 3 months before screening * Has used opioid agonists (eg, codeine, oxycodone, tramadol, morphine) or opioid antagonists (eg, naloxone, naltrexone) within 14 days prior to screening * Has received electroconvulsive therapy treatment within the last 2 years or within the current MDE or failed a course of electroconvulsive treatment at any time * Has a significant risk for suicide * Has a positive breath alcohol test at screening * Has a positive test for drugs of abuse at screening or visit 2 * Is pregnant, planning to become pregnant, or is breastfeeding during the study * Additional criteria may apply