A Study to Compare the Efficacy, Safety, and Tolerability of JNJ-42847922 Versus Quetiapine Extended-Release as Adjunctive Therapy to Antidepressants in Adult Participants With Major Depressive Disorder Who Have Responded Inadequately to Antidepressant Therapy

Percentage of Participants With Sustained Remission up to Week 24

Remission is defined as Montgomery-Asberg Depression Rating Scale (MADRS) total score of less than or equal to (\<=) 12. A participant was defined as having achieved sustained remission if the MADRS total score was ≤12 at Week 12 and was sustained at Weeks 18 and 24. Participants with missing values at a given time point were imputed as non-evaluable for remission. MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score range of 0-60 which is calculated by adding the scores of all 10 items. Higher scores represent a more severe condition.

Time frame: Up to Week 24

Percentage of Participants With Sustained Response up to Week 24

A participant was defined as having achieved a sustained response if there was at least a 50% improvement from baseline in the MADRS total score at Week 12, and that response was maintained at Week 18 and Week 24. Participants who did not meet such criterion were considered as non-sustained responders. MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score range of 0-60 which is calculated by adding the scores of all 10 items. Higher scores represent a more severe condition.

Time frame: Up to Week 24

Change From Baseline in MADRS Total Score in Participants With Significant Insomnia (Baseline Insomnia Severity Index [ISI] Score >=15) Versus Those Without Significant Insomnia (Baseline ISI Score Less Than [<] 15) at Week 12

MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score range of 0-60 which is calculated by adding the scores of all 10 items. Higher scores represent a more severe condition. The ISI has 7 questions, each rated on a 5-point Likert scale ranging from 0 to 4. The total score is calculated as the sum of the 7 items ranging from 0 to 28. Higher scores represent a more severe condition.

Time frame: Baseline and Week 12

Change From Baseline in MADRS Total Score in Participants With Significant Insomnia (Baseline ISI Score >=15) Versus Those Without Significant Insomnia (Baseline ISI Score <15) at Week 18

MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score range of 0-60 which is calculated by adding the scores of all 10 items. Higher scores represent a more severe condition. The ISI has 7 questions, each rated on a 5-point Likert scale ranging from 0 to 4. The total score is calculated as the sum of the 7 items ranging from 0 to 28. Higher scores represent a more severe condition.

Time frame: Baseline and Week 18

Change From Baseline in MADRS Total Score in Participants With Significant Insomnia (Baseline ISIscore >=15) Versus Those Without Significant Insomnia (Baseline ISI Score 15) at Week 24

MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score range of 0-60 which is calculated by adding the scores of all 10 items. Higher scores represent a more severe condition. The ISI has 7 questions, each rated on a 5-point Likert scale ranging from 0 to 4. The total score is calculated as the sum of the 7 items ranging from 0 to 28. Higher scores represent a more severe condition.

Time frame: Baseline and Week 24

Change From Baseline in the Hamilton Anxiety Rating Scale (HAM-A) Total Score at Weeks 12, 18, and 24

HAM-A is a 14-item scale designed to measure anxiety in individuals. Each question reflects a symptom of anxiety and physical as well as mental symptoms are represented. Each of the 14-items in the scale is scored on a 5-point scale, ranging from 0 (a complete lack of that symptom) to 4 (a very severe show of anxiety with that symptom). The total score ranges from 0 to 56 which is calculated by adding the scores of all 14 items, where 0-13 indicates normal range, 14-17 indicates mild severity, 18 -24: mild to moderate severity, 25 -30: moderate to severe, and \>=31: severe. Higher score indicates worsening. Negative change in score indicates improvement.

Time frame: Baseline, Weeks 12, 18, and 24

Percentage of Participants With Weight Gain of >=7% of Baseline Body Weight at Week 24

Percentage of participants with weight gain of \>=7% of baseline body weight at Week 24 were reported.

Time frame: At Week 24

Percentage of Participants With Shifts in Triglycerides From Normal to High

Percentage of participants with shifts in triglycerides from normal to high (\<150 milligrams per deciliter \[mg/dL\] at baseline to \>=200 mg/dL at any post-baseline assessment) were reported.

Time frame: Up to Week 24

Percentage of Participants With Shifts in Triglycerides From Borderline to High

Percentage of participants with shifts in triglycerides from borderline to high (\>=150 to \<200 mg/dL at baseline to \>=200 mg/dL at any post-baseline assessment) were reported.

Time frame: Up to Week 24

Percentage of Participants With Shifts in Triglycerides From Normal to Very High

Percentage of participants with shifts in triglycerides from normal to very high (\<150 mg/dL at baseline to \>=500 mg/dL at any post-baseline assessment) were reported.

Time frame: Up to Week 24

Percentage of Participants With Shifts in Triglycerides From Borderline to Very High

Percentage of participants with shifts in triglycerides from borderline to very high (\>=150 mg/dL to \<200 mg/dL at baseline to \>=500 mg/dL at any post-baseline assessment) were reported.

Time frame: Up to Week 24

Percentage of Participants With Shifts in Triglycerides From High to Very High

Percentage of participants with shifts in triglycerides from high to very high (\>=200 mg/dL to \<500 mg/dL at baseline to \>=500 mg/dL at any post-baseline assessment) were reported.

Time frame: Up to Week 24

Percentage of Participants With Shifts in Fasting Blood Glucose From Normal to Borderline

Percentage of participants with shifts in fasting blood glucose from normal to borderline (\<100 mg/dL at baseline to between \>=100 and \<126 mg/dL at any post-baseline assessment) were reported.

Time frame: Up to Week 24

Percentage of Participants With Shifts in Fasting Blood Glucose From Borderline to High

Percentage of participants with shifts in fasting blood glucose from borderline to high (\>=100 to \<126 mg/dL at baseline to \>=126 mg/dL at any post-baseline assessment) were reported.

Time frame: Up to Week 24

Percentage of Participants With Shifts in Fasting Blood Glucose From Normal to High

Percentage of participants with shifts in fasting blood glucose from normal to high (\<100 mg/dL at baseline to \>=126 mg/dL at any post-baseline assessment) were reported.

Time frame: Up to Week 24

Change From Baseline in the Clinical Global Impression-Severity (CGI-S) Scale Score at Weeks 12 and 24

The CGI-S provides an overall clinician-determined summary measure of the severity of the participant's illness that takes into account all available information, including knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. The CGI-S is a 7-point global assessment scale that measures the clinician's impression of the severity of illness exhibited by a participant, rating according to: 1=normal (not at all ill); 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7=among the most extremely ill participants. Higher scores indicate worsening. Negative change in score indicates improvement.

Time frame: Baseline, Weeks 12 and 24

Change From Baseline in the Patient Global Impression Severity (PGI-S) Scale Score at Weeks 12 and 24

The PGI-S is a self-report scale to measure severity of illness (1=none, 2=mild, 3=moderate, 4=severe). Higher score indicates more illness severity. Negative change in score indicates improvement.

Time frame: Baseline, Weeks 12 and 24

Change From Baseline in Quality of Life in Depression Scale (QLDS) Score at Weeks 12 and 24

The QLDS is a disease specific patient-reported outcome (PRO) designed to assess health related quality of life in participants with major depressive disorder (MDD). The instrument has a recall period of "at the present time", contains 34-items with "true"/"not true" response options. Each statement on the QLDS is given a score of "1" (adverse quality of life) or "0" good quality of life. All item scores are summed to give a total score that ranges from 0 (good quality of life) to 34 (very poor quality of life). A higher score indicates a more severe condition. Negative change indicates improvement.

Time frame: Baseline, Weeks 12 and 24

Change From Baseline in Patient Reported Outcomes Measurement Information System-Sleep Disturbance (PROMIS-SD) Short Form 8a at Weeks 12 and 24

The PROMIS-SD Short Form 8a subscale consists of a static 8 item questionnaire. It assesses the concepts of sleep initiation (2 items), quality of sleep (3 items), early morning feelings (2 items) and worrying about sleep (1 item). Responses to each of the 8 items range from 1 to 5, and the range of possible summed raw scores is 8 to 40. Higher scores on the PROMIS-SD indicate more of the concept measured (disturbed sleep). Negative change in score indicates improvement.

Time frame: Baseline, Weeks 12 and 24

Change From Baseline in Patient Reported Outcomes Measurement Information System-Sleep Related Impairment (PROMIS-SRI) Short Form 8a at Weeks 12 and 24

The PROMIS-SRI Short Form 8a subscale consists of a static 8 item questionnaire and use five-point likert scale to capture the participant's impressions. It assesses sleep-related impairment over the past 7 days. Responses to each of the 8 items range from 1 (less impairment) to 5 (more impairment), and the range of possible summed raw scores is 8 to 40. Lower scores indicate less sleep related impairment. Negative change in score indicates improvement.

Time frame: Baseline, Weeks 12 and 24

Change From Baseline in Symptoms of Major Depressive Disorder Scale (SMDDS) Score at Weeks 12 and 24

The SMDDS assesses participant-reported symptoms associated with MDD. This 16-item instrument has a 7-day recall period, and participants respond to each question using a rating scale between 0 ("Not at all" or "Never") to 4 ("Extremely" or "Always"). Before summing the items to create a total score, item 11 ("how often did you have a poor appetite") and item 12 ("how often did you over eat") are combined into a single score by selecting the highest severity on either item. The total score is then created by summing the responses on the 15 items. The total score ranges from 0 to 60 with a higher score indicating more severe depressive symptomatology. Negative change in score indicates improvement.

Time frame: Baseline, Weeks 12 and 24

Change From Baseline in Symbol Digit Modalities Test (SDMT) at Weeks 6, 12, and 24

SDMT is a widely used, paper-and-pencil assessment of complex scanning and visual tracking, requiring elements of attention, visuoperceptual processing, working memory, and cognitive/psychomotor speed. The test is viewed as a robust screening test for adult neuropsychological impairment and is sensitive to impairments in cognitive function associated with MDD. The SDMT measured the time to pair abstract symbols with specific numbers. The test included a coding key consisting of 9 abstract symbols, each paired with a number ranging from 1 to 9. Following the key, the participant was presented with randomly ordered symbols and was required to write the number corresponding to each symbol as fast as possible. The number of correct substitutions within 90 seconds was recorded and total score derived from the total number of correct responses with a minimum possible score of 0 and maximum of 110 where high scores indicate better outcome. Positive change in score indicates improvement.

Time frame: Baseline, Weeks 6, 12, and 24

Change From Baseline in Trail Making Test - Part B (TMT-Part B) at Weeks 6, 12, and 24

The TMT-Part B measures divided attention and executive function (tracking and sequencing). The participant is instructed to draw a line to connect a set of 25 consecutively numbered and lettered circles, alternating sequentially between numbers and letters (that is, 1 A 2 B). The participant is instructed to work as quickly as possible while still maintaining accuracy. Score included time (seconds) to completion and number of errors in performing the test which ranges from 0 (no errors) to 25 (more errors), where shorter time and less number of errors indicates better performance. The TMT-Part B is sensitive to cognitive decline associated with MDD. Negative change in score indicates improvement.

Time frame: Baseline, Weeks 6, 12, and 24

Change From Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) at Weeks 6, 12, and 24

The HVLT-R measures performance in verbal memory, learning, and long-term recall in which a list of words is read up to three times. Approximately 20-25 minutes later, a delayed recall trial and a recognition trial are completed. The delayed recall requires free recall of any words remembered. The recognition trial is composed of 24 words, including the 12 target words and 12 false-positives. When scoring the HVLT, the three learning trials are combined to calculate a total recall score (0-36); the delayed recall trial creates the delayed recall score (0 -12); the total number of true-positive errors (0-12); and the recognition discrimination index is comprised by subtracting the total number of false positives from the total number of true positives. A higher score indicates higher cognition.

Time frame: Baseline, Weeks 6, 12, and 24

Change From Baseline in Salivary Cortisol Levels as Measured at Home Upon Awakening and During the Evening at Weeks 6 and 24

Change from baseline in salivary cortisol levels as measured upon awakening and at home during the evening at Weeks 6 and 24 were reported.

Time frame: Baseline, Weeks 6 and 24

Percentage of Participants With Treatment-emergent Adverse Events as a Measure of Safety and Tolerability

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Treatment-emergent AEs were AEs with onset during the double-blind treatment phase or that were a consequence of a preexisting condition that worsened since baseline.

Time frame: Up to 24 weeks

Percentage of Participants With Treatment-emergent Serious Adverse Events (SAEs) and Events of Special Interest

An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was any untoward medical occurrence that at any dose may result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a suspected transmission of any infectious agent via a medicinal product. AESIs were significant AEs that were judged to be of special interest because of clinical importance, known or suspected class effects, or based on nonclinical signals. Adverse events of special interest were cataplexy, sleep paralysis, complex, and sleep-related behaviors (parasomnias).

Time frame: Up to 24 weeks

Percentage of Participants With Abnormalities in Vital Sign Parameters

Percentage of participants with abnormalities in vital sign parameters (pulse, supine and standing blood pressure \[systolic and diastolic\], body temperature, and body weight) were reported. Abnormally low values for parameters included pulse (beats per minute)- decrease value from baseline (\>=) 15 to \<=50; Systolic Blood Pressure (BP) (mmHg \[Millimeter of mercury\])- decrease value from baseline \>=20 to \<=90; Diastolic BP- decrease value from baseline \>=15 to \<=50; weight (Kilogram\[Kg\])- decrease from baseline of \>=7%; Body temperature (Celsius \[C\])- \<35.5. Abnormally high values for parameters included pulse- increase value from baseline \>=15 to \>=100; Systolic BP(mmHg)- increase from baseline of \>=20 to \>=180; Diastolic BP- increase value from baseline \>=15 to \>=105; weight(Kg)- increase from baseline of \>=7%; body temperature (C)- \>37.5.

Time frame: Up to 24 weeks

Percentage of Participants With Abnormalities in Electrocardiogram (ECG) Parameters

Percentage of participants with abnormalities in ECG parameters were reported.

Time frame: Up to 24 weeks

Percentage of Participants With Abnormalities in Clinical Laboratory Parameters

Percentage of participants with abnormalities in clinical laboratory parameters were reported.

Time frame: Up to 24 weeks

Percentage of Participants With Sexual Dysfunction as Determined by Arizona Sexual Experiences Scale (ASEX) Total Score

Sexual dysfunction is defined as an ASEX total score of 19 or greater, or a score of 5 or greater on any item, or a score of 4 or greater on any 3 items. ASEX is a five-item rating scale that quantifies sex drive, arousal, vaginal lubrication/penile erection, ability to reach orgasm, and satisfaction from orgasm. Each of the 5 items is rated on a 6-point Likert scale, ranging from 1 to 6. The 5 items are summed to create a total score, ranging from 5 to 30, with the higher scores indicating more sexual dysfunction.

Time frame: Up to Endpoint (Up to 24 weeks)

Percentage of Participants With Clinically Relevant Changes in Extrapyramidal Symptoms Assessed by the Extrapyramidal Symptom Rating Scale-Abbreviated (ESRS-A) Score

The ESRS-A is an abbreviated manualized version of the ESRS, a semi-structured interview that rates parkinsonian symptoms, dystonia, dyskinesias, and akathisia over the previous 7 days. The ratings include a motor examination for rigidity, tremor, reduced facial expression or speech, impaired gait/posture, postural instability, and bradykinesia/hypokinesia. Twenty-four individual items are rated on a 6-point scale: 0=Absent, 1=Minimal, 2=Mild, 3=Moderate, 4=Severe, or 5=Extreme. Frequency is included as an index of severity.

Time frame: Up to Endpoint (Up to 24 weeks)

Percentage of Participants With Suicidality Assessed Using Columbia Suicide Severity Rating Scale (C-SSRS) Score

C-SSRS is a clinician-rated instrument that reports severity and frequency of suicide-related ideation and behaviors. Suicidal ideation was classified on a 5-item scale: 1 (wish to be dead), 2 (non-specific active suicidal thoughts), 3 (active suicidal ideation with any methods \[not plan\] without intent to act), 4 (active suicidal ideation with some intent to act, without specific plan), and 5 (active suicidal ideation with specific plan and intent). Suicidal behavior is classified on a 5-item scale: 6 (preparatory acts or behavior), 7 (aborted attempt), 8 (interrupted attempt), 9 (actual attempt \[non-fatal\]), and 10 (completed suicide \[only applicable for post baseline\]). Minimum total score 0, maximum total score 10; higher total scores indicate more suicidal ideation and/or suicidal behavior. If no events qualify for score of 1 to 10, score of 0 was assigned (0= "no event that can be assessed on the basis of C-SSRS"). Higher scores indicate greater severity.

Time frame: Up to Endpoint (Up to 24 weeks)

Percentage of Participant With Potential Withdrawal Effects Assessed by the Physician Withdrawal Checklist (PWC)

Intensity of discontinuation symptoms was assessed (anxiety-nervousness, dysphoric mood/depression, Depersonalization-Derealization, , Diaphoresis, Diarrhea, Difficulty Concentrating, Remember, Dizziness-Lightheadedness, Fatigue-Lethargy-Lack of Energy, Headaches, Increased Acuity Sound Smell Touch, Irritability, Loss of Appetite, Muscle Aches or Stiffness, Nausea-Vomiting, Paresthesias, Poor Coordination, Restlessness-Agitation, Tremor-Tremulousness, Weakness), using the Physician Withdrawal Checklist (PWC-20) administered by a trained clinician/rater. Symptoms are rated on a scale of 0 (no symptom present), 1 (mild), 2 (moderate), and 3 (severe). Total scores range from 0 (no symptom) to 24 (severe symptom) calculated by adding the scores of following 8 items: Nausea-Vomiting, Diarrhea, Poor Coordination, Diaphoresis, Tremor-Tremulousness, Dizziness-Lightheadedness, Increased Acuity Sound Smell Touch, Paresthesias. Higher scores indicates more severe symptoms.

Time frame: Up to 26 weeks

Change From Baseline in MADRS Total Score Over Time

MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score range of 0-60 which is calculated by adding the scores of all 10 items. Higher scores represent a more severe condition.

Time frame: Baseline, Weeks 2, 4, 6, 12, 18, 24

Change From Baseline in MADRS Total Score Over Time, by Mode Dose

MADRS is a clinician-administered scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates the following 10 items: apparent sadness, reported sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts. Each item is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score range of 0-60 which is calculated by adding the scores of all 10 items. Higher scores represent a more severe condition. Negative change in score indicates improvement.

Time frame: Baseline, Weeks 2, 4, 6, 12, 18, 24, and 26

Change From Baseline in MADRS-6 Score Over Time

MADRS-6 is the depression subscale of the full MADRS, including the following 6 items: apparent sadness, reported sadness, inner tension, lassitude, inability to feel, pessimistic thoughts. Each item is scored from 0 (absence of symptom) to 6 (severe symptom); the overall score ranges from 0 to 36 which is calculated by adding the scores of all 6 items. Higher scores represent a more severe condition.

Time frame: Baseline, Weeks 2, 4, 6, 12, 18, 24, and 26