Participants must have completed a previous study phase or meet specific medical criteria, including being medically stable and having a history of major depressive disorder (MDD).

Participants should be aged between 18 and 74 years and have an inadequate response to at least one oral antidepressant treatment in the current episode of depression.

Participants undergo a physical examination, medical history review, vital signs check, and a 12-lead ECG to ensure medical stability.

Clinical laboratory tests are performed to confirm eligibility.

Participants receive aticaprant in the form of a tablet for oral use.

Aticaprant is administered as an adjunctive therapy to a current antidepressant, which is either a selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI).

Regular monitoring of adverse events (AEs), including those of special interest, is conducted.

Changes in vital signs, weight, and body mass index (BMI) are tracked.

Suicidality is assessed using the Columbia Suicidality Severity Rating Scale (C-SSRS).

Laboratory parameters and 12-lead ECGs are regularly evaluated.

Withdrawal symptoms are assessed using the Physician Withdrawal Checklist, 20-item (PWC-20).

The proportion of participants with clinically relevant sexual dysfunction is monitored over time using the Arizona Sexual Experiences Scale (ASEX) score.

The study is designed to last up to one year, with an estimated end date of December 1, 2025.