The percentage of participants achieving a response (defined as a ≥50% improvement from baseline on the HAMD21 total score) was calculated by dividing the number of participants achieving a response at last observation by the total number of participants at risk, multiplied by 100.

The percentage of participants achieving a remission (defined as a HAMD21 total score ≤7) was calculated by dividing the number of participants achieving a remission at last observation by the total number of participants at risk, multiplied by 100.

CGI-S measures severity of illness at the time of assessment with scores ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). LS means were calculated using MMRM adjusting for the random effect of participant and fixed categorical effects of treatment, pooled investigative site, visit, and treatment-by-visit interaction, as well as the continuous fixed covariate of baseline CGI-S score.

HAMD17 total scores and subscale scores from the HAMD21 are presented. HAMD17 is a 17-item assessment of depression severity (total scores range from 0-52). The Maier subscale (Items 1, 2, 7-10) represents the core symptoms of depression (0-24). Anxiety/Somatization subscale (Items 10-13, 15, 17) evaluates severity of psychic and somatic manifestations of anxiety as well as agitation (0-18). Retardation/Somatization subscale (Items 1, 7, 8, 14) evaluates dysfunction in mood, work, and sexual activity, as well as overall motor retardation (0-14). Sleep subscale (Items 4-6) assesses insomnia (0-6). Individual item scores may range from 0-4 or 0-2. Higher scores indicate more severe symptoms. LS means were calculated using MMRM adjusting for the random effect of participant and fixed categorical effects of treatment, pooled investigative site, visit, and treatment-by-visit interaction, as well as the continuous fixed covariate of baseline score.

SDS was completed by the participant and was used to assess the effect of the participant's symptoms on their work/school (Item 1), social life/leisure activities (Item 2), and family life/home responsibilities (Item 3). Each item was measured on a 0 (not at all) to 10 (extremely) point scale with higher values indicating greater disruption. Total score was the sum of the 3 items and ranged from 0 to 30 with higher values indicating greater disruption in the participant's work/social/family life. LS means were calculated using analysis of covariance (ANCOVA) adjusting for treatment, pooled investigative site, and baseline SDS score.

Participants randomized to fluoxetine 40 mg/day in Study B1Y-JE-HCLV and continued on fluoxetine (20-40 mg/day) in Study B1Y-JE-HCLW.

Total of all reporting groups

Participants randomized to fluoxetine 40 mg/day in Study B1Y-JE-HCLV and continued on fluoxetine (20-40 mg/day) in Study B1Y-JE-HCLW.

C-SSRS captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal behavior is defined as a "yes" answer to any of 5 suicidal behavior questions: preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide. Suicidal ideation is defined as a "yes" answer to any one of 5 suicidal ideation questions: wish to be dead, and 4 different categories of active suicidal ideation.

Participants who received at least 1 dose of study drug with at least 1 post-baseline C-SSRS score during Study Period 1.

HAMD21 is a 21-item assessment used to measure depression severity. Items were rated on a scale from 0 (symptoms not present) to a maximum of 2 to 4 (symptom extremely severe) for a total score ranging from 0 (not at all depressed) to 64 (severely depressed). Least squares (LS) means were calculated using mixed-model repeated measures (MMRM) adjusting for the random effect of participant and fixed categorical effects of treatment, pooled investigative site, visit, and treatment-by-visit interaction, as well as the continuous fixed covariate of baseline HAMD21 total score.

Participants who received at least 1 dose of study drug with a baseline and at least 1 post-baseline HAMD21 total score during Study Period 1.

The percentage of participants achieving a response (defined as a ≥50% improvement from baseline on the HAMD21 total score) was calculated by dividing the number of participants achieving a response at last observation by the total number of participants at risk, multiplied by 100.

Participants who received at least 1 dose of study drug with a baseline and at least 1 post-baseline HAMD21 total score during the Treatment Period. Missing endpoints were imputed with the last observation carried forward (LOCF) method, using only post-baseline data.

The percentage of participants achieving a remission (defined as a HAMD21 total score ≤7) was calculated by dividing the number of participants achieving a remission at last observation by the total number of participants at risk, multiplied by 100.

Participants who received at least 1 dose of study drug with a baseline (which had not achieved remission threshold criteria) and had at least 1 post-baseline HAMD21 total score during the Treatment Period. Missing endpoints were imputed with the last observation carried forward (LOCF) method, using only post-baseline data.

CGI-S measures severity of illness at the time of assessment with scores ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). LS means were calculated using MMRM adjusting for the random effect of participant and fixed categorical effects of treatment, pooled investigative site, visit, and treatment-by-visit interaction, as well as the continuous fixed covariate of baseline CGI-S score.

Participants who received at least 1 dose of study drug with a baseline and at least 1 post-baseline CGI-S score during the Treatment Period.

HAMD17 total scores and subscale scores from the HAMD21 are presented. HAMD17 is a 17-item assessment of depression severity (total scores range from 0-52). The Maier subscale (Items 1, 2, 7-10) represents the core symptoms of depression (0-24). Anxiety/Somatization subscale (Items 10-13, 15, 17) evaluates severity of psychic and somatic manifestations of anxiety as well as agitation (0-18). Retardation/Somatization subscale (Items 1, 7, 8, 14) evaluates dysfunction in mood, work, and sexual activity, as well as overall motor retardation (0-14). Sleep subscale (Items 4-6) assesses insomnia (0-6). Individual item scores may range from 0-4 or 0-2. Higher scores indicate more severe symptoms. LS means were calculated using MMRM adjusting for the random effect of participant and fixed categorical effects of treatment, pooled investigative site, visit, and treatment-by-visit interaction, as well as the continuous fixed covariate of baseline score.

Participants who received at least 1 dose of study drug with a baseline and at least 1 post-baseline HAMD21 subscale score. LSM (least square mean) and SE (standard error) are from visit 16.

SDS was completed by the participant and was used to assess the effect of the participant's symptoms on their work/school (Item 1), social life/leisure activities (Item 2), and family life/home responsibilities (Item 3). Each item was measured on a 0 (not at all) to 10 (extremely) point scale with higher values indicating greater disruption. Total score was the sum of the 3 items and ranged from 0 to 30 with higher values indicating greater disruption in the participant's work/social/family life. LS means were calculated using analysis of covariance (ANCOVA) adjusting for treatment, pooled investigative site, and baseline SDS score.

Participants who received at least 1 dose of study drug with a baseline and at least 1 post-baseline SDS score. Missing endpoints were imputed with the last observation carried forward (LOCF) method, using only post-baseline data.

Participants randomized to fluoxetine 20 mg/day in Study B1Y-JE-HCLV and continued on fluoxetine (20-40 mg/day) in Study B1Y-JE-HCLW.

Participants randomized to fluoxetine 40 mg/day in Study B1Y-JE-HCLV and continued on fluoxetine (20-40 mg/day) in Study B1Y-JE-HCLW.

Participants in the PLA/FLX group in Study Period 1, and discontinuing from fluoxetine in Study Period 2,

Participants in the FLX20/FLX group in Study Period 1, and discontinuing from fluoxetine in Study Period 2.

Participants in the FLX40/FLX group in Study Period 1, and discontinuing from fluoxetine in Study Period 2.