A study to evaluate if aticaprant added to a current antidepressant and given up to one year is safe and would help improve depression.

Prior treatment

• Has a current homicidal ideation/intent, per the investigator's clinical judgment, or has suicidal ideation with some intent to act within 3 months prior to the start of the screening phase
• Participant has taken any prohibited therapies that would not permit dosing on Day 1, as noted in the pre-study and concomitant therapy section.
• Has a history or evidence of clinically meaningful noncompliance with current antidepressant therapy.
• Has a history of moderate-to-severe substance use disorder including alcohol use disorder according to DSM-5 criteria within 6 months before screening.
• Has had in the current episode an inadequate response to adequate course of intravenous or intranasal ketamine or esketamine, electroconvulsive therapy (i.e, at least 7 treatments), vagal nerve stimulation, or a deep brain stimulation device

Other illness

• Participant has any condition or situation/circumstance for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
• Direct-entry participants: - Have had in the current depressive episode, no response (treatment failure) to 5 or more antidepressant treatments including the current SSRI/SNRI

Other

• Transferred-entry participants: - Participant has been non-compliant with the study intervention administration in the Double Blind (DB) Treatment Phase in either of Studies 67953964MDD3001 or 67953964MDD3002
• The evaluation of the benefit versus risk of continued aticaprant treatment is not favorable for the participant in the opinion of the investigator.
• Participant is reporting suicidal ideation with intent to act or suicidal behavior at baseline.

• Transferred patients: - Participants must have completed the Double Blind Treatment Phase of Study 67953964MDD3001 or Study 67953964MDD3002 study.
• Participant must be medically stable on the basis of physical examination, medical history, vital signs (including blood pressure), and 12-lead ECG performed at baseline and prior to Open Label treatment initiation.
• Direct entry patients: - Male or female, aged 18 to 74 years of age, inclusive.
• Be medically stable on the basis of physical examination, medical history, vital signs, and 12-lead ECG performed at screening and baseline
• Be medically stable on the basis of clinical laboratory tests performed at screening
• Meet DSM-5 diagnostic criteria for recurrent or single episode MDD, without psychotic features. Participants 65 years of age or older must have had the first onset of depression prior to 55 years of age.
• Have had an inadequate response to at least 1 oral antidepressant treatment, administered at an adequate dose and duration in the current episode of depression.
• Is receiving and tolerating well a SSRI/SNRI for depressive symptoms at screening, at a stable dose for at least 6 weeks
• Have a HDRS-17 total score of 20 or higher at the first and second screening interviews and must not demonstrate a clinically significant improvement between the first and the second independent HDRS-17 assessments