Placebo tablet will be administered orally.

Change from baseline over time in MADRS total score is reported. The MADRS is a clinician-rated scale designed to measure depression severity and detect changes due to antidepressant treatment. The scale consists of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms). MADRS total score is the sum of scores from individual question items, which ranges from 0 to 60; higher scores represent a more severe condition. Negative change in MADRS total score indicates improvement.

Percentage of participants who achieved response on depressive symptoms scale based on MADRS total score at Day 43 are reported. Responders are defined as participants with a >=50 percent (%) improvement in the MADRS total score from baseline to a given timepoint. The MADRS is a clinician-rated scale designed to measure depression severity and detect changes due to antidepressant treatment. The scale consists of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms). MADRS total score is the sum of scores from individual question items, which ranges from 0 to 60; higher scores represent a more severe condition. Negative change in MADRS total score indicates improvement.

Percentage of participants with remission of depressive symptoms based on MADRS total score at Day 43 is reported. Participant is defined as a remitter at a given time point if the MADRS total score is less than or equal to (<=)10 at that time point. The MADRS is a clinician-rated scale designed to measure depression severity and detect changes due to antidepressant treatment. The scale consists of 10 items (apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms). MADRS total score is the sum of scores from individual question items, which ranges from 0 to 60; higher scores represent a more severe condition. Negative change in MADRS total score indicates improvement.

Change from baseline to Day 43 in PHQ-9 total score is reported. The PHQ-9 is a 9-item, participant reported outcome measure to assess depressive symptoms. The scale scores each of the 9 symptom domains of the Diagnostic and Statistical Manual of Mental Disorders-5th Edition (DSM-5) MDD criteria. Each item is rated on a 4 point scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The participant's item responses are summed to provide a total score (range of 0 to 27), with higher scores indicating greater severity of depressive symptoms. The severity of the PHQ-9 is categorized as follows: none-minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19) and severe (20-27). Negative changes in PHQ-9 total score indicate improvement.

Change from baseline over time in DARS total score is reported. The DARS is a 17-item self-report questionnaire that is designed to assess anhedonia in MDD across the 4 domains: hobbies, social activities, food/drink, and sensory experience. The DARS scale measures desire, motivation, effort, and consummatory pleasure. The DARS is rated on a 5-point Likert scale (0=not at all, 1=slightly, 2=moderately, 3=mostly, 4=very much) and responses are summed to generate the total score (range of 0 to 68). A lower total score is indicative of greater anhedonia. Positive changes in DARS total score indicate improvement.

Change from baseline over time in the PHQ-9 anhedonia-specific item (PHQ-9, item 1 is little interest or pleasure in doing things) is reported. The PHQ-9 is a 9-item, participant reported outcome measure to assess depressive symptoms. The scale scores each of the 9 symptom domains of the Diagnostic and Statistical Manual of Mental Disorders-5th Edition (DSM-5) MDD criteria. Each item is rated on a 4 point scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The participant's item responses are summed to provide a total score (range of 0 to 27), with higher scores indicating greater severity of depressive symptoms. The severity of the PHQ-9 is categorized as follows: none-minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19) and severe (20-27). PHQ-9, item 1 score ranged from 0-3. Higher score indicates more severe disease. Negative change in PHQ-9, item 1 score indicates improvement.

Percentage of participants with a score <2 in the PHQ-9 anhedonia-specific item (PHQ-9, item 1 is little interest or pleasure in doing things) at Day 43 is reported. The PHQ-9 is a 9-item, participant reported outcome measure to assess depressive symptoms. The scale scores each of the 9 symptom domains of the Diagnostic and Statistical Manual of Mental Disorders-5th Edition (DSM-5) MDD criteria. Each item is rated on a 4 point scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The participant's item responses are summed to provide a total score (range of 0 to 27), with higher scores indicating greater severity of depressive symptoms. The severity of the PHQ-9 is categorized as follows: none-minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19) and severe (20-27).

Change from baseline over time in the PROMIS-APS 8a is reported. This 8-item measure assesses participants' ability to participate in social roles and activities. The items measures the degree of involvement in social roles, activities, and responsibilities, including work, family, friends, and leisure. Each item is rated on a 5-point ordinal scale including 1=always, 2=usually, 3=sometimes, 4=rarely and 5=never, with higher scores indicating better social functioning. The total scores of PROMIS-APS 8a are scaled on a T-score metric with a mean of 50 and a standard deviation of 10. PROMIS-APS 8a total score ranges from 8 to 40 and T-score ranges from 25.9 to 65.4, a higher score indicates better social functioning. Positive change in score indicates improvement.

Percentage of participants with TEAEs during DB treatment phase are reported. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAE is defined as any AE occurring at or after the initial administration of study intervention through the end of DB phase.

Percentage of participants with AEs during FU phase are reported. An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention.

During DB treatment phase, participants received aticaprant 10 milligrams (mg) tablet orally once daily from Day 1 to Day 42 in addition to the ongoing antidepressant therapy (SSRI/SNRI). Participants were then followed up for safety up to 7 to 14 days after end of DB phase at Day 43 (up to Day 57). Participants who completed the DB phase (at Day 43) and were compliant to the study intervention were eligible to participate in a separate 52-week open-label long-term safety study 67953964MDD3003 (NCT05518149).

During DB treatment phase, participants received aticaprant 10 milligram (mg) tablet orally once daily from Day 1 to Day 42 in addition to the ongoing antidepressant therapy (SSRI/SNRI). Participants were then followed up for safety up to 7 to 14 days after end of DB phase at Day 43 (up to Day 57). Participants who completed the DB phase (at Day 43) and were compliant to the study intervention were eligible to participate in a separate 52-week open-label long-term safety study 67953964MDD3003 (NCT05518149).

During DB treatment phase, participants received aticaprant 10 milligram (mg) tablet orally once daily from Day 1 to Day 42 in addition to the ongoing antidepressant therapy (SSRI/SNRI). Participants were then followed up for safety up to 7 to 14 days after end of DB phase at Day 43 (up to Day 57). Participants who completed the DB phase (at Day 43) and were compliant to the study intervention were eligible to participate in a separate 52-week open-label long-term safety study 67953964MDD3003 (NCT05518149).

During DB treatment phase, participants received aticaprant 10 milligram (mg) tablet orally once daily from Day 1 to Day 42 in addition to the ongoing antidepressant therapy (SSRI/SNRI). Participants were then followed up for safety up to 7 to 14 days after end of DB phase at Day 43 (up to Day 57). Participants who completed the DB phase (at Day 43) and were compliant to the study intervention were eligible to participate in a separate 52-week open-label long-term safety study 67953964MDD3003 (NCT05518149).

During DB treatment phase, participants received aticaprant 10 milligram (mg) tablet orally once daily from Day 1 to Day 42 in addition to the ongoing antidepressant therapy (SSRI/SNRI). Participants were then followed up for safety up to 7 to 14 days after end of DB phase at Day 43 (up to Day 57). Participants who completed the DB phase (at Day 43) and were compliant to the study intervention were eligible to participate in a separate 52-week open-label long-term safety study 67953964MDD3003 (NCT05518149).

During DB treatment phase, participants received aticaprant 10 milligram (mg) tablet orally once daily from Day 1 to Day 42 in addition to the ongoing antidepressant therapy (SSRI/SNRI). Participants were then followed up for safety up to 7 to 14 days after end of DB phase at Day 43 (up to Day 57). Participants who completed the DB phase (at Day 43) and were compliant to the study intervention were eligible to participate in a separate 52-week open-label long-term safety study 67953964MDD3003 (NCT05518149).

During DB treatment phase, participants received aticaprant 10 milligram (mg) tablet orally once daily from Day 1 to Day 42 in addition to the ongoing antidepressant therapy (SSRI/SNRI). Participants were then followed up for safety up to 7 to 14 days after end of DB phase at Day 43 (up to Day 57). Participants who completed the DB phase (at Day 43) and were compliant to the study intervention were eligible to participate in a separate 52-week open-label long-term safety study 67953964MDD3003 (NCT05518149).

During DB treatment phase, participants received aticaprant 10 milligram (mg) tablet orally once daily from Day 1 to Day 42 in addition to the ongoing antidepressant therapy (SSRI/SNRI). Participants were then followed up for safety up to 7 to 14 days after end of DB phase at Day 43 (up to Day 57). Participants who completed the DB phase (at Day 43) and were compliant to the study intervention were eligible to participate in a separate 52-week open-label long-term safety study 67953964MDD3003 (NCT05518149).

During DB treatment phase, participants received aticaprant 10 milligram (mg) tablet orally once daily from Day 1 to Day 42 in addition to the ongoing antidepressant therapy (SSRI/SNRI). Participants were then followed up for safety up to 7 to 14 days after end of DB phase at Day 43 (up to Day 57). Participants who completed the DB phase (at Day 43) and were compliant to the study intervention were eligible to participate in a separate 52-week open-label long-term safety study 67953964MDD3003 (NCT05518149).

During DB treatment phase, participants received aticaprant 10 milligram (mg) tablet orally once daily from Day 1 to Day 42 in addition to the ongoing antidepressant therapy (SSRI/SNRI). Participants were then followed up for safety up to 7 to 14 days after end of DB phase at Day 43 (up to Day 57). Participants who completed the DB phase (at Day 43) and were compliant to the study intervention were eligible to participate in a separate 52-week open-label long-term safety study 67953964MDD3003 (NCT05518149).