QIDS-SR16 is a 16-item, participant-rated measure of depressive symptomatology with 4 possible answers per question that are specific to the question. Each question (Q) is scored from 0 (no problems) to 3 (increased symptoms). The total score for each visit is the sum of 9 of the 16 items: the highest number from Q1-4 (sleep), number from Q5 (feeling sad), highest number from Q6-9 (appetite and weight), total for Q10-14 (concentration, view of self, thoughts of death or suicide, general interest and energy level respectively) and the highest number from Q15-16 (psychomotor changes). The total score ranges from 0 to 27 with higher scores indicating greater severity of depression. Least Squares (LS) means are calculated using mixed model repeating measures (MMRM) and adjusted for treatment, investigator, visit, treatment-by-visit, baseline score, and baseline-by-visit.

Intent-to-treat population analysis is determined by the treatment groups to which participants are randomly assigned regardless of treatment received, and includes all participants who do not meet response criteria during Weeks 1-2, have baseline and at least 1 post-baseline QIDS-SR16 Total Score.

QIDS-SR16 is a 16-item, participant-rated measure of depressive symptomatology with 4 possible answers per question that are specific to the question. Each question (Q) is scored from 0 (no problems) to 3 (increased symptoms). The total score for each visit is the sum of 9 of the 16 items: the highest number from Q1-4 (sleep), number from Q5 (feeling sad), highest number from Q6-9 (appetite and weight), total for Q10-14 (concentration, view of self, thoughts of death or suicide, general interest and energy level respectively) and the highest number from Q15-16 (psychomotor changes). Least Squares (LS) means are calculated using mixed model repeated measure (MMRM) and adjusted for treatment, investigator, visit, treatment-by-visit, baseline score, and baseline-by-visit.

Intent-to-treat population analysis is determined by the treatment groups to which participants are randomly assigned regardless of treatment received, and includes all participants who do not meet response criteria during Weeks 1-2, have baseline and at least 1 post-baseline QIDS-SR16 Individual Score.

The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS is a 10-item checklist with items rated on a scale of 0-6, for a total scores range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Least Squares (LS) means are calculated using mixed model repeating measures (MMRM) and adjusted for investigator, treatment-by-visit, baseline score, and baseline-by-visit.

Intent-to-treat population analysis is determined by the treatment groups to which participants are randomly assigned regardless of treatment received, and includes all participants who do not meet response criteria during Weeks 1-2, have baseline and at least 1 post-baseline MADRS Total Score.

HADS is a 14-item questionnaire with 2 subscales: anxiety and depression. Each item is rated on a 4-point scale (0-3), giving maximum scores of 21 for each subscale. Scores of 11 or more on either subscale are considered to be a significant 'case' of psychological morbidity, while scores of 8-10 represent 'borderline' and 0-7 is 'normal.' Least Squares (LS) means are calculated using analysis of covariance (ANCOVA) and adjusted for treatment, investigator, visit, treatment-by-visit, investigator, and baseline score.

Intent-to-treat population analysis is determined by the treatment groups to which participants are randomly assigned regardless of treatment received, and includes all participants who do not meet response criteria during Weeks 1-2, have baseline and at least 1 post-baseline HADS Score; last observation carried forward (LOCF).

CGI-S measures severity of illness at the time of assessment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). Least Squares (LS) means are calculated using mixed model repeated measures (MMRM) and adjusted for treatment, investigator, visit, treatment-by visit, baseline score, and baseline-by-visit.

Intent-to-treat population analysis is determined by the treatment groups to which participants are randomly assigned regardless of treatment received, and includes all participants who do not meet response criteria during Weeks 1-2, have baseline and at least 1 post-baseline CGI-Severity Score.

The CPFQ is a 7-item participant-rated questionnaire pertaining to a participant's cognitive and physical well-being. It assesses motivation, wakefulness, energy, focus, recall, word-finding difficulty, and mental acuity. Each item is scored on a 6-point scale ranging from 1 (greater than normal) to 6 (totally absent). Total score ranges from 7 to 42. Higher scores indicate greater disease severity. Least Squares (LS) means are calculated using mixed model repeated measures (MMRM) and adjusted for treatment, investigator, visit, treatment-by-visit, baseline score, and baseline-by-visit.

Intent-to-treat population analysis is determined by the treatment groups to which participants are randomly assigned regardless of treatment received, and includes all participants who do not meet response criteria during Weeks 1-2, have baseline and at least 1 post-baseline CPFQ Total Score.

The FAsD PRO is a 16-item participant-rated scale. Seven items ask how often the participants experience different aspects of fatigue with each item rated on a 5-point scale: 1 (Never) to 5 (Always). Nine items ask how often fatigue impacts various aspects of the participants lives with each item rated on a 5-point scale: 1 (Not at all) to 5 (Very much). The Fatigue Experience Score is the mean of Items 1-5, and 7, the Fatigue Impact Score is the mean of Items 8-12, 14, and 16, and the Overall Average Score is the mean of Items 1-5, 7-12, 14 and 16. The Experience, Impact and Overall Mean Scores range from 1 to 5, lower scores indicate less experience/impact. Least Squares (LS) means are calculated using analysis of covariance (ANCOVA) and adjusted for treatment, investigator, and baseline score.

Intent-to-treat population analysis is determined by the treatment groups to which participants are randomly assigned regardless of treatment received, and includes all participants who do not meet response criteria during Weeks 1-2, have baseline and at least 1 post-baseline FAsD-PRO Score; last observation carried forward (LOCF).

VAS-F is a self-rated assessment on 2 items: the overall severity of fatigue and the interferences with daily activities due to fatigue. For the overall severity of fatigue the participant is asked to place a vertical mark on a 100 millimeter (mm) line between 2 anchors: 0 (not at all) and 100 (as severe as I can imagine). For the interference with daily activities due to fatigue, the participant is asked to place a vertical mark on a 100 mm line between 2 anchors: 0 (not at all) and 100 [complete disability (unable to do any activities)]. Least Squares (LS) means are calculated using analysis of covariance (ANCOVA) and adjusted for treatment, investigator, and baseline score.

Intent-to-treat population analysis is determined by the treatment groups to which participants are randomly assigned regardless of treatment received, and includes all participants who do not meet response criteria during Weeks 1-2, have baseline and at least 1 post-baseline VAS-F Score; last observation carried forward (LOCF).

VAS-P is a self-rated assessment for 2 items: the overall severity of pain and the interferences with daily activities due to pain. For the overall severity of pain the participant is asked to place a vertical mark on a 100 millimeter (mm) line between 2 anchors: 0 (not at all) and 100 (as severe as I can imagine). For the interference with daily activities due to pain, the participant is asked to place a vertical mark on a 100-mm line between 2 anchors: 0 (not at all) and 100 [complete disability (unable to do any activities)]. Least Squares (LS) means are calculated using analysis of covariance (ANCOVA) and adjusted for treatment, investigator, and baseline score.

Intent-to-treat population analysis is determined by the treatment groups to which participants are randomly assigned regardless of treatment received, and includes all participants who do not meet response criteria during Weeks 1-2, have baseline and at least 1 post-baseline VAS-P Score; last observation carried forward (LOCF).

The SDS is a 3-item, participant completed assessment and is used to assess the effect of the participant's symptoms on their work/social/family life. The Global Functional Impairment Total Score is a total of the 3 individual item scores, each with a scores range from 0 (not at all) to 10 (extremely). The Global Functional Impairment Total Scores range from 0 to 30 with higher values indicating greater disruption in the participant's work/social/family life. Least Squares (LS) means are calculated using analysis of covariance (ANCOVA) and adjusted for treatment, investigator, and baseline score.

Intent-to-treat analysis is determined by treatment group participants are randomly assigned regardless of treatment received, includes all participants who do not respond in Weeks 1-2, have baseline and at least 1 post-baseline SDS Total Score; last observation carried forward. Missing work score imputed with average of other 2-item scores.

The Q-LES-Q-SF is a self-administered 16-item questionnaire measuring degree of enjoyment and satisfaction experienced in various areas of daily life during the past week, and is rated on a 5-point Likert scale: 1 (very poor) to 5 (very good). The Q-LES-Q-SF Total Raw Score is the sum of Items 1 to 14 and ranges from 14 to 70. The Q-LES-Q-SF Raw Scores are converted to, and expressed as the percentage of the maximum possible score. Higher scores indicate higher levels of enjoyment/satisfaction. Least Squares (LS) means are calculated using analysis of covariance (ANCOVA) and adjusted for treatment, investigator, and baseline score.

Intent-to-treat analysis is determined by treatment group participants are randomly assigned regardless of treatment received, includes all participants who do not respond in Weeks 1-2, have baseline and at least 1 post-baseline Q-LES-Q-SF Total Score; last observation carried forward. If ≤2 items are missing mean of all other items are imputed.

The MGH-SFQ is a 6-item participant-rated scale quantifying sexual interest, arousal (subjective excitement), ability to reach orgasm, erectile function (for males), and overall satisfaction and are scored on a 6-point scale: 1 (greater than normal) to 6 (totally absent); and overall improvement since last medication change is scored on a 6-point scale: 1 (very much improved) to 6 (much worse). Least Squares (LS) means are calculated using analysis of covariance (ANCOVA) and adjusted for treatment, investigator, and baseline score.

Intent-to-treat population analysis is determined by the treatment groups to which participants are randomly assigned regardless of treatment received, and includes all participants who do not meet response criteria during Weeks 1-2, have baseline and at least 1 post-baseline MGH-SFQ Score.

Percent of participants with suicidal ideation, behavior and acts based on C-SSRS. The C-SSRS scale captures occurrence, severity, and frequency of suicide-related thoughts and behaviors. Suicidal behavior: a "yes" answer to any 1 of 5 suicidal behavior questions (preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt, and completed suicide). Suicidal ideation: a "yes" answer to any 1 of 5 suicidal ideation questions (wish to be dead, and 4 different categories of active suicidal ideation). Suicidal act: a "yes" answer to actual attempt or completed suicide.

Intent-to-treat population analysis is determined by the treatment groups to which participants are randomly assigned regardless of treatment received, and includes all participants who do not meet response criteria during Weeks 1-2, have baseline and at least 1 post-baseline C-SSRS Score.

Blood pressure is collected while the participant is in the supine position. Least Squares (LS) means are calculated using mixed model repeated measures (MMRM) and adjusted for treatment, investigator, visit, treatment-by-visit, baseline score, and baseline-by-visit.

Intent-to-treat population analysis is determined by the treatment groups to which participants are randomly assigned regardless of treatment received, and includes all participants who have baseline and at least 1 post-baseline supine systolic and diastolic blood pressure measure.

Pulse is collected while the participant is in the supine position. Least Squares (LS) means are calculated using mixed model repeated measures (MMRM) and adjusted for treatment, investigator, visit, treatment-by-visit, baseline score, and baseline-by-visit.

Intent-to-treat population analysis is determined by the treatment groups to which participants are randomly assigned regardless of treatment received, and included all participants who have baseline and at least 1 post-baseline supine pulse rate measure.