Trial Outcomes & Findings for 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 (NCT NCT03321526)

Results Overview

Time to all-cause discontinuation of study drug is defined as the number of days from the first dose of study drug to the last dose of study drug. Participants who completed double-blind treatment were not considered to have discontinued.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

107 participants

Primary outcome timeframe

Up to Week 24

Results posted on

2025-04-29

Participant Flow

Participant milestones

Participant milestones
Measure	Seltorexant Participants in the double-blind treatment phase received seltorexant 20 milligrams (mg) tablet orally once daily as the starting dose on Day 1. From Day 14, participants received either seltorexant 20 mg or 40 mg up to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).	Quetiapine XR Participants in the double-blind treatment phase received quetiapine XR 50 mg once daily for the first two days and then 150 mg tablets orally once daily from Day 3 to Day 14. From Day 14, participants received either quetiapine XR 150 mg or 300 mg up to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).
Double-blind Treatment Phase (24 Weeks) STARTED	54	53
Double-blind Treatment Phase (24 Weeks) COMPLETED	30	27
Double-blind Treatment Phase (24 Weeks) NOT COMPLETED	24	26
Follow-up Phase (2 Weeks) STARTED	54	52
Follow-up Phase (2 Weeks) COMPLETED	30	28
Follow-up Phase (2 Weeks) NOT COMPLETED	24	24

Reasons for withdrawal

Reasons for withdrawal
Measure	Seltorexant Participants in the double-blind treatment phase received seltorexant 20 milligrams (mg) tablet orally once daily as the starting dose on Day 1. From Day 14, participants received either seltorexant 20 mg or 40 mg up to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).	Quetiapine XR Participants in the double-blind treatment phase received quetiapine XR 50 mg once daily for the first two days and then 150 mg tablets orally once daily from Day 3 to Day 14. From Day 14, participants received either quetiapine XR 150 mg or 300 mg up to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).
Double-blind Treatment Phase (24 Weeks) Lost to Follow-up	2	2
Double-blind Treatment Phase (24 Weeks) Withdrawal by Subject	9	3
Double-blind Treatment Phase (24 Weeks) Lack of Efficacy	1	3
Double-blind Treatment Phase (24 Weeks) Adverse Event	7	8
Double-blind Treatment Phase (24 Weeks) Death	1	0
Double-blind Treatment Phase (24 Weeks) Non-Compliance with Study Drug	3	6
Double-blind Treatment Phase (24 Weeks) Other	1	4
Follow-up Phase (2 Weeks) Other	24	24

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Seltorexant n=52 Participants Participants in the double-blind treatment phase received seltorexant 20 milligrams (mg) tablet orally once daily as the starting dose on Day 1. From Day 14, participants received either seltorexant 20 mg or 40 mg up to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).	Quetiapine XR n=52 Participants Participants in the double-blind treatment phase received quetiapine XR 50 mg once daily for the first two days and then 150 mg tablets orally once daily from Day 3 to Day 14. From Day 14, participants received either quetiapine XR 150 mg or 300 mg up to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).	Total n=104 Participants Total of all reporting groups
Age, Continuous	55.3 years STANDARD_DEVIATION 9.67 • n=5 Participants	53.6 years STANDARD_DEVIATION 10.83 • n=7 Participants	54.5 years STANDARD_DEVIATION 10.26 • n=5 Participants
Age, Customized Adults (18-64 years)	43 Participants n=5 Participants	43 Participants n=7 Participants	86 Participants n=5 Participants
Age, Customized From 65 to 84 years	9 Participants n=5 Participants	9 Participants n=7 Participants	18 Participants n=5 Participants
Age, Customized 85 years and over	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	34 Participants n=5 Participants	35 Participants n=7 Participants	69 Participants n=5 Participants
Sex: Female, Male Male	18 Participants n=5 Participants	17 Participants n=7 Participants	35 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	17 Participants n=5 Participants	10 Participants n=7 Participants	27 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	34 Participants n=5 Participants	41 Participants n=7 Participants	75 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	14 Participants n=5 Participants	14 Participants n=7 Participants	28 Participants n=5 Participants
Race (NIH/OMB) White	36 Participants n=5 Participants	36 Participants n=7 Participants	72 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment UNITED STATES	52 Participants n=5 Participants	52 Participants n=7 Participants	104 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Week 24

Population: Full analysis set included all randomized participants who received at least 1 dose of study drug except 2 participants who received potentially defective investigational products (IPs) and were subsequently discontinued early because of the IP issues.

Time to all-cause discontinuation of study drug is defined as the number of days from the first dose of study drug to the last dose of study drug. Participants who completed double-blind treatment were not considered to have discontinued.

Outcome measures

Outcome measures
Measure	Seltorexant n=51 Participants Participants in the double-blind treatment phase received seltorexant 20 milligrams (mg) tablet orally once daily as the starting dose on Day 1. From Day 14, participants received either seltorexant 20 mg or 40 mg up to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).	Quetiapine XR n=51 Participants Participants in the double-blind treatment phase received quetiapine XR 50 mg once daily for the first two days and then 150 mg tablets orally once daily from Day 3 to Day 14. From Day 14, participants received either quetiapine XR 150 mg or 300 mg up to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).	Quetiapine XR 150 mg Participants in the double-blind treatment phase received flexibly dosed quetiapine XR 50 mg once daily for the first two days and then 150 mg tablets orally once daily from Day 3 to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).	Quetiapine XR 300 mg Participants in the double-blind treatment phase received flexibly dosed quetiapine XR 50 mg once daily for the first two days and then 300 mg tablets orally once daily from Day 3 to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).
Time to All-Cause Discontinuation of Study Drug	NA days NA refers that median and 80 percent (%) confidence interval (CI) were not estimable as fewer than 50% of participants withdrew from the study.	NA days NA refers that median and 80% CI were not estimable as fewer than 50% of participants withdrew from the study.	—	—

SECONDARY outcome

Timeframe: Up to Week 24

Population: Full analysis set included all randomized participants who received at least 1 dose of study drug except 2 participants who received potentially defective IPs and were subsequently discontinued early because of the IP issues. Here, N (number of participants analyzed) signifies number of participants that were evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Seltorexant n=38 Participants Participants in the double-blind treatment phase received seltorexant 20 milligrams (mg) tablet orally once daily as the starting dose on Day 1. From Day 14, participants received either seltorexant 20 mg or 40 mg up to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).	Quetiapine XR n=36 Participants Participants in the double-blind treatment phase received quetiapine XR 50 mg once daily for the first two days and then 150 mg tablets orally once daily from Day 3 to Day 14. From Day 14, participants received either quetiapine XR 150 mg or 300 mg up to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).	Quetiapine XR 150 mg Participants in the double-blind treatment phase received flexibly dosed quetiapine XR 50 mg once daily for the first two days and then 150 mg tablets orally once daily from Day 3 to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).	Quetiapine XR 300 mg Participants in the double-blind treatment phase received flexibly dosed quetiapine XR 50 mg once daily for the first two days and then 300 mg tablets orally once daily from Day 3 to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).
Percentage of Participants With Sustained Remission up to Week 24	13.2 percentage of participants	19.4 percentage of participants	—	—

SECONDARY outcome

Timeframe: Up to Week 24

Population: Full analysis set included all randomized participants who received at least 1 dose of study drug except 2 participants who received potentially defective IPs and were subsequently discontinued early because of the IP issues. Here, N (number of participants analyzed) signifies number of participants that were evaluable for this outcome measure.

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.

Outcome measures

Outcome measures
Measure	Seltorexant n=38 Participants Participants in the double-blind treatment phase received seltorexant 20 milligrams (mg) tablet orally once daily as the starting dose on Day 1. From Day 14, participants received either seltorexant 20 mg or 40 mg up to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).	Quetiapine XR n=36 Participants Participants in the double-blind treatment phase received quetiapine XR 50 mg once daily for the first two days and then 150 mg tablets orally once daily from Day 3 to Day 14. From Day 14, participants received either quetiapine XR 150 mg or 300 mg up to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).	Quetiapine XR 150 mg Participants in the double-blind treatment phase received flexibly dosed quetiapine XR 50 mg once daily for the first two days and then 150 mg tablets orally once daily from Day 3 to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).	Quetiapine XR 300 mg Participants in the double-blind treatment phase received flexibly dosed quetiapine XR 50 mg once daily for the first two days and then 300 mg tablets orally once daily from Day 3 to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).
Percentage of Participants With Sustained Response up to Week 24	13.2 percentage of participants	22.2 percentage of participants	—	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Full analysis set included all randomized participants who received at least 1 dose of study drug except 2 participants who received potentially defective IPs and were subsequently discontinued early because of the IP issues. Here, N (number of participants analyzed) signifies number of participants that were evaluable for this outcome measure and n (number analyzed) signifies those participants who were evaluable for specific categories.

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.

Outcome measures

Outcome measures
Measure	Seltorexant n=38 Participants Participants in the double-blind treatment phase received seltorexant 20 milligrams (mg) tablet orally once daily as the starting dose on Day 1. From Day 14, participants received either seltorexant 20 mg or 40 mg up to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).	Quetiapine XR n=35 Participants Participants in the double-blind treatment phase received quetiapine XR 50 mg once daily for the first two days and then 150 mg tablets orally once daily from Day 3 to Day 14. From Day 14, participants received either quetiapine XR 150 mg or 300 mg up to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).	Quetiapine XR 150 mg Participants in the double-blind treatment phase received flexibly dosed quetiapine XR 50 mg once daily for the first two days and then 150 mg tablets orally once daily from Day 3 to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).	Quetiapine XR 300 mg Participants in the double-blind treatment phase received flexibly dosed quetiapine XR 50 mg once daily for the first two days and then 300 mg tablets orally once daily from Day 3 to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).
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 Baseline ISI score <15	-10.4 score on a scale Standard Deviation 12.68	-12.8 score on a scale Standard Deviation 9.67	—	—
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 Baseline ISI score >=15	-13.4 score on a scale Standard Deviation 10.73	-17.3 score on a scale Standard Deviation 9.70	—	—

SECONDARY outcome

Timeframe: Baseline and Week 18

Population: Full analysis set included all randomized participants who received at least 1 dose of study drug except 2 participants who received potentially defective IPs and were subsequently discontinued early because of the IP issues. Here, N (number of participants analyzed) signifies number of participants that were evaluable for this outcome measure and n (number analyzed) signifies those participants who were evaluable for specific categories.

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.

Outcome measures

Outcome measures
Measure	Seltorexant n=34 Participants Participants in the double-blind treatment phase received seltorexant 20 milligrams (mg) tablet orally once daily as the starting dose on Day 1. From Day 14, participants received either seltorexant 20 mg or 40 mg up to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).	Quetiapine XR n=31 Participants Participants in the double-blind treatment phase received quetiapine XR 50 mg once daily for the first two days and then 150 mg tablets orally once daily from Day 3 to Day 14. From Day 14, participants received either quetiapine XR 150 mg or 300 mg up to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).	Quetiapine XR 150 mg Participants in the double-blind treatment phase received flexibly dosed quetiapine XR 50 mg once daily for the first two days and then 150 mg tablets orally once daily from Day 3 to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).	Quetiapine XR 300 mg Participants in the double-blind treatment phase received flexibly dosed quetiapine XR 50 mg once daily for the first two days and then 300 mg tablets orally once daily from Day 3 to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).
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 Baseline ISI score <15	-13.9 score on a scale Standard Deviation 16.66	-16.2 score on a scale Standard Deviation 10.46	—	—
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 Baseline ISI score >=15	-10.3 score on a scale Standard Deviation 14.96	-12.9 score on a scale Standard Deviation 11.58	—	—

SECONDARY outcome

Timeframe: Baseline and Week 24

Population: Full analysis set included all randomized participants who received at least 1 dose of study drug except 2 participants who received potentially defective IPs and were subsequently discontinued early because of the IP issues. Here, N (number of participants analyzed) signifies number of participants that were evaluable for this outcome measure. and n (number analyzed) signifies those participants who were evaluable for specific categories.

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.

Outcome measures

Outcome measures
Measure	Seltorexant n=30 Participants Participants in the double-blind treatment phase received seltorexant 20 milligrams (mg) tablet orally once daily as the starting dose on Day 1. From Day 14, participants received either seltorexant 20 mg or 40 mg up to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).	Quetiapine XR n=27 Participants Participants in the double-blind treatment phase received quetiapine XR 50 mg once daily for the first two days and then 150 mg tablets orally once daily from Day 3 to Day 14. From Day 14, participants received either quetiapine XR 150 mg or 300 mg up to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).	Quetiapine XR 150 mg Participants in the double-blind treatment phase received flexibly dosed quetiapine XR 50 mg once daily for the first two days and then 150 mg tablets orally once daily from Day 3 to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).	Quetiapine XR 300 mg Participants in the double-blind treatment phase received flexibly dosed quetiapine XR 50 mg once daily for the first two days and then 300 mg tablets orally once daily from Day 3 to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).
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 Baseline ISI score <15	-14.3 score on a scale Standard Deviation 14.47	-15.6 score on a scale Standard Deviation 8.78	—	—
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 Baseline ISI score >=15	-13.5 score on a scale Standard Deviation 14.32	-15.4 score on a scale Standard Deviation 11.76	—	—

SECONDARY outcome

Timeframe: Baseline, Weeks 12, 18, and 24

Population: Full analysis set included all randomized participants who received at least 1 dose of study drug except 2 participants who received potentially defective IPs and were subsequently discontinued early because of the IP issues. Here, 'N' (numbers of participants analyzed) signifies numbers of participants evaluable for this outcome measure; 'n' (number analyzed) signifies those participants who were evaluable at specified timepoints for specific timepoints.

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.

Outcome measures

Outcome measures
Measure	Seltorexant n=37 Participants Participants in the double-blind treatment phase received seltorexant 20 milligrams (mg) tablet orally once daily as the starting dose on Day 1. From Day 14, participants received either seltorexant 20 mg or 40 mg up to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).	Quetiapine XR n=33 Participants Participants in the double-blind treatment phase received quetiapine XR 50 mg once daily for the first two days and then 150 mg tablets orally once daily from Day 3 to Day 14. From Day 14, participants received either quetiapine XR 150 mg or 300 mg up to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).	Quetiapine XR 150 mg Participants in the double-blind treatment phase received flexibly dosed quetiapine XR 50 mg once daily for the first two days and then 150 mg tablets orally once daily from Day 3 to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).	Quetiapine XR 300 mg Participants in the double-blind treatment phase received flexibly dosed quetiapine XR 50 mg once daily for the first two days and then 300 mg tablets orally once daily from Day 3 to Day 168 (Week 24) while continuing their current selective serotonin reuptake inhibitor (SSRI) or serotonin-norepinephrine reuptake inhibitor (SNRI) antidepressant on which they had an inadequate response at the time of screening. Participants had a follow-up visit within 7 to 14 days after double-blind treatment phase. During the follow-up phase, participants were followed-up for the safety assessments on Day 182 (Week 26).
Change From Baseline in the Hamilton Anxiety Rating Scale (HAM-A) Total Score at Weeks 12, 18, and 24 Week 12	-8.7 units on a scale Standard Deviation 6.05	-6.6 units on a scale Standard Deviation 6.75	—	—
Change From Baseline in the Hamilton Anxiety Rating Scale (HAM-A) Total Score at Weeks 12, 18, and 24 Week 18	-8.5 units on a scale Standard Deviation 6.66	-10.0 units on a scale Standard Deviation 5.69	—	—
Change From Baseline in the Hamilton Anxiety Rating Scale (HAM-A) Total Score at Weeks 12, 18, and 24 Week 24	-10.9 units on a scale Standard Deviation 6.55	-9.5 units on a scale Standard Deviation 7.26	—	—

SECONDARY outcome

Timeframe: At Week 24

Population: Safety analysis set included all randomized participants who received at least 1 dose of study drug including the 2 participants who received the potentially defective IP. Here, 'N' (numbers of participants analyzed) signifies number of participants evaluable for this outcome measure with at least one post-baseline value.

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