A Study of Aticaprant 10 mg as Adjunctive Therapy in Adult Participants With Major Depressive Disorder (MDD) With Moderate-to-severe Anhedonia and Inadequate Response to Current Antidepressant Therapy and Long-term Extension Treatment With Aticaprant

Inclusion Criteria:

• Be medically stable based on physical examination (including a brief neurologicexamination), medical history, vital signs (including blood pressure), and 12-leadelectrocardiogram (ECG) performed at screening and double blind (DB) baseline

• Meet diagnostic and statistical manual of mental disorders-5th edition (DSM-5)diagnostic criteria for recurrent or single episode major depressive disorder (MDD),without psychotic features (DSM-5 296.22, 296.23, 296.32, or 296.33), based uponclinical assessment and confirmed by the structured clinical interview for DSM-5axis I disorders-clinical trials version (SCID-CT)

• Have symptoms of anhedonia based on clinical assessment and confirmed by presence ofanhedonia (positive response to MDE module symptom Item 2) on the SCID-CT atscreening

• Have had an inadequate response to at least 1 and up to 5 (inclusive) oralantidepressant treatments, administered at an adequate dose

• Is currently receiving and tolerating well any one of the following selectiveserotonin reuptake inhibitor or serotonin-norepinephrine reuptake inhibitor (SSRI orSNRI) antidepressants at screening, in any approved formulation and available in theparticipating country/territory: citalopram, duloxetine, escitalopram, fluvoxamine,fluoxetine, milnacipran, levomilnacipran, paroxetine, sertraline, venlafaxine, ordesvenlafaxine at a stable dose (at or above the minimum therapeutic dose perMassachusetts general hospital antidepressant treatment response questionnaire (MGHATRQ) for at least 6 weeks. The current antidepressant cannot be the firstantidepressant treatment for the first lifetime episode of depression

Exclusion Criteria:

• Has had no response (treatment failure) to 2 or more consecutive antidepressanttreatments administered at an adequate dose (at or above the minimum therapeuticdose) and duration (at least 6 weeks) in the current episode of depression includingthe current SSRI/SNRI (that is the one to be continued in the treatment phases)assessed using the MGH ATRQ

• Has one or more of the following diagnoses: (1) a current or prior (lifetime) DSM-5diagnosis of: (a) a psychotic disorder or MDD with psychotic features, (b) bipolaror related disorders, (c) intellectual disability, (d) autism spectrum disorder, (e)borderline personality disorder, (f) antisocial personality disorder, (g) histrionicpersonality disorder, (h) narcissistic personality disorders, (i) somatoformdisorders; (2) A primary DSM-5 diagnosis (which has been the primary focus ofpsychiatric treatment within the past 2 years) of: (a) panic disorder, (b)generalized anxiety disorder, (c) social anxiety disorder, (d) specific phobia; (3)A current (in the past year) DSM-5 diagnosis of: (a) obsessive-compulsive disorder, (b) post-traumatic stress disorder, (c) anorexia nervosa, (d) bulimia nervosa

• Has a history or evidence of clinically meaningful noncompliance with currentantidepressant therapy

• Has a history of moderate-to-severe substance use disorder including alcohol usedisorder according to DSM-5 criteria within 6 months before screening

• Has in the current depressive episode had vagal nerve stimulation or deep brainstimulation device in the current episode or has had an inadequate response to anadequate course of intravenous or intranasal ketamine or esketamine (greater than [>] 2 treatments), or electroconvulsive therapy (that is at least 7 treatments)

• Has homicidal ideation/intent, per the investigator's clinical judgment, or hassuicidal ideation with some intent to act within 3 months prior to the start of thescreening phase, per the investigator's clinical judgment or based on the columbiasuicidality severity rating scale (C-SSRS), corresponding to a response of "Yes" onItem 4 (active suicidal ideation with some intent to act, without specific plan) orItem 5 (active suicidal ideation with specific plan and intent) for suicidalideation on the C-SSRS, or a history of suicidal behavior within the past 6 monthsprior to the start of the screening phase. Participants reporting suicidal ideationwith intent to act or suicidal behavior at DB baseline should be excluded