Trial Outcomes & Findings for Vortioxetine, 5, 10, and 20 mg, Relapse Prevention Study in Adults With Major Depressive Disorder (MDD) (NCT NCT02371980)

NCT ID: NCT02371980

Last Updated: 2021-01-06

Results Overview

Relapse was defined as either 1) MADRS Score ≥22, 2) lack of efficacy as determined by the investigator or 3) other unsatisfactory treatment response judged by the investigator. Time to relapse was defined as date of relapse - date of randomization + 1 (where date of relapse is the date of last dose, or date of last contact if date of last dose is missing, for participant with a relapse). Participants without relapse were censored at date of withdrawal or date of Week 28 visit, whichever was earliest. MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score ranges from 0 to 60. Higher scores indicate greater severity of symptoms. The inter-quartile range (IQR) was 25th percentile to 75th percentile.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

1106 participants

Primary outcome timeframe

From date of double-blind randomization (Week 16) up to relapse or first 28 weeks of Double-blind Period which occurs first (Up to Week 44)

Results posted on

2021-01-06

Participant Flow

Participants took part in the study at 74 investigative sites in the United States from 10 February 2015 to 25 April 2019.

Participants with diagnosis of major depressive disorder (MDD) were enrolled to receive vortioxetine 10 mg in the Open-label Period for up to 16 weeks. Responders (defined below) were randomized in 1:1:1:1 ratio to receive vortioxetine 5 mg, 10 mg or 20 mg or placebo for up to 32 weeks in the Double-blind Period.

Participant milestones

Participant milestones
Measure	Open-label: Vortioxetine 10 mg Vortioxetine 10 mg, capsules, orally, once, daily (QD) up to 8 weeks. Participants who achieved response (defined as a ≥50% reduction in Montgomery Asberg Depression Rating Scale (MADRS) total score from Baseline) continued to receive vortioxetine 10 mg, capsules, orally, QD for up to Week 16 (stabilization period) in the Open-label Period.	Double-blind: Placebo Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine placebo-matching capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.	Double-blind: Vortioxetine 5 mg Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 5 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.	Double-blind: Vortioxetine 10 mg Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 10 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.	Double-blind: Vortioxetine 20 mg Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 20 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Open-label Period STARTED	1106	0	0	0	0
Open-label Period COMPLETED	580	0	0	0	0
Open-label Period NOT COMPLETED	526	0	0	0	0
Double-blind Period STARTED	0	151	140	145	144
Double-blind Period COMPLETED	0	70	84	96	86
Double-blind Period NOT COMPLETED	0	81	56	49	58

Reasons for withdrawal

Reasons for withdrawal
Measure	Open-label: Vortioxetine 10 mg Vortioxetine 10 mg, capsules, orally, once, daily (QD) up to 8 weeks. Participants who achieved response (defined as a ≥50% reduction in Montgomery Asberg Depression Rating Scale (MADRS) total score from Baseline) continued to receive vortioxetine 10 mg, capsules, orally, QD for up to Week 16 (stabilization period) in the Open-label Period.	Double-blind: Placebo Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine placebo-matching capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.	Double-blind: Vortioxetine 5 mg Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 5 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.	Double-blind: Vortioxetine 10 mg Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 10 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.	Double-blind: Vortioxetine 20 mg Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 20 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Open-label Period Pretreatment Event/Adverse Event	63	0	0	0	0
Open-label Period Significant Protocol Deviation	19	0	0	0	0
Open-label Period Noncompliance with Study Drug	10	0	0	0	0
Open-label Period Lost to Follow-up	55	0	0	0	0
Open-label Period Voluntary Withdrawal	91	0	0	0	0
Open-label Period Pregnancy	1	0	0	0	0
Open-label Period Lack of Efficacy	116	0	0	0	0
Open-label Period Did not Meet Randomization Criteria	162	0	0	0	0
Open-label Period Reason not Specified	9	0	0	0	0
Double-blind Period Pretreatment Event/Adverse Event	0	4	3	2	9
Double-blind Period Significant Protocol Deviation	0	2	7	3	3
Double-blind Period Noncompliance with Study Drug	0	1	2	2	3
Double-blind Period Lost to Follow-up	0	8	8	6	5
Double-blind Period Voluntary Withdrawal	0	12	8	9	11
Double-blind Period Relapse	0	50	25	25	26
Double-blind Period Reason not Specified	0	3	3	2	1
Double-blind Period Missing	0	1	0	0	0

Baseline Characteristics

Vortioxetine, 5, 10, and 20 mg, Relapse Prevention Study in Adults With Major Depressive Disorder (MDD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Open-label: Vortioxetine 10 mg n=1106 Participants Vortioxetine 10 mg, capsules, orally, once, daily (QD) up to 8 weeks. Participants who achieved response (defined as a ≥50% reduction in Montgomery Asberg Depression Rating Scale (MADRS) total score from Baseline) continued to receive vortioxetine 10 mg, capsules, orally, QD for up to Week 16 (stabilization period) in the Open-label Period.
Age, Continuous	44.3 years STANDARD_DEVIATION 13.69 • n=5 Participants
Sex: Female, Male Female	807 Participants n=5 Participants
Sex: Female, Male Male	299 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	145 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	961 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	7 Participants n=5 Participants
Race (NIH/OMB) Asian	19 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	10 Participants n=5 Participants
Race (NIH/OMB) Black or African American	258 Participants n=5 Participants
Race (NIH/OMB) White	790 Participants n=5 Participants
Race (NIH/OMB) More than one race	19 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants
Region of Enrollment United States	1106 Participants n=5 Participants
Height	167.7 cm STANDARD_DEVIATION 9.38 • n=5 Participants
Weight	82.92 kg STANDARD_DEVIATION 18.695 • n=5 Participants
Body Mass Index (BMI)	29.39 kg/m^2 STANDARD_DEVIATION 5.731 • n=5 Participants
Smoking Classification Participant has Never Smoked	705 Participants n=5 Participants
Smoking Classification Participant is a Current Smoker	215 Participants n=5 Participants
Smoking Classification Participant is an Ex-smoker	186 Participants n=5 Participants
Alcohol Consumption Participant has Never Consumed	332 Participants n=5 Participants
Alcohol Consumption Consumes Once Monthly or Less Consumes Often	286 Participants n=5 Participants
Alcohol Consumption Consumes Once a Week	167 Participants n=5 Participants
Alcohol Consumption Consumes 2 to 6 Times per Week	159 Participants n=5 Participants
Alcohol Consumption Consumes Daily	11 Participants n=5 Participants
Alcohol Consumption Participant was an Ex-Drinker	151 Participants n=5 Participants

PRIMARY outcome

Timeframe: From date of double-blind randomization (Week 16) up to relapse or first 28 weeks of Double-blind Period which occurs first (Up to Week 44)

Population: Full Analysis Set (FAS) included all participants who were randomized in the double-blind period and received at least 1 dose of double-blind study drug.

Outcome measures

Outcome measures
Measure	Double-blind: Vortioxetine 10 mg n=145 Participants Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 10 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.	Double-blind: Vortioxetine 20 mg n=144 Participants Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 20 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.	Double-blind: Vortioxetine 5 mg n=140 Participants Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 5 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.	Double-blind: Placebo n=151 Participants Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine placebo-matching capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Time From Randomization to Relapse of Major Depressive Disorder During the First 28 Weeks of the 32-Week Double-Blind Treatment Period	NA weeks Interval 28.0 to Median and upper limit of IQR were not reached due to low number of participants with events.	NA weeks Interval 28.0 to Median and upper limit of IQR were not reached due to low number of participants with events.	NA weeks Interval 28.0 to Median and upper limit of IQR were not reached due to low number of participants with events.	NA weeks Interval 12.0 to Median and upper limit of IQR were not reached due to low number of participants with events.

SECONDARY outcome

Timeframe: Double-blind Baseline (BL) II and Double-blind Period: Weeks 2, 4, 8, 12, 16, 20, 24, 28, and 32

Population: FAS included all participants who were randomized in the double-blind period and received at least 1 dose of double-blind study drug. Number analyzed is the number of participants with data available for analysis at the given time-point.

MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score range from 0 to 60. Higher score indicates greater severity of symptoms. Baseline II is defined as the last non-missing observation prior to the first dose of double-blind study drug. Mixed model for repeated measures (MMRM) was used for analyses.

Outcome measures

Outcome measures
Measure	Double-blind: Vortioxetine 10 mg n=145 Participants Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 10 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.	Double-blind: Vortioxetine 20 mg n=144 Participants Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 20 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.	Double-blind: Vortioxetine 5 mg n=140 Participants Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 5 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.	Double-blind: Placebo n=151 Participants Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine placebo-matching capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Change From BL II at Week 2	1.47 scores on scale Standard Error 0.471	2.29 scores on scale Standard Error 0.481	2.23 scores on scale Standard Error 0.490	2.70 scores on scale Standard Error 0.461
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Change From BL II at Week 4	1.98 scores on scale Standard Error 0.581	2.48 scores on scale Standard Error 0.602	2.56 scores on scale Standard Error 0.599	4.99 scores on scale Standard Error 0.576
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Change From BL II at Week 8	2.14 scores on scale Standard Error 0.679	2.97 scores on scale Standard Error 0.708	3.03 scores on scale Standard Error 0.698	5.98 scores on scale Standard Error 0.688
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Change From BL II at Week 12	1.92 scores on scale Standard Error 0.684	2.79 scores on scale Standard Error 0.707	3.51 scores on scale Standard Error 0.701	6.43 scores on scale Standard Error 0.704
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Change From BL II at Week 16	2.08 scores on scale Standard Error 0.688	3.14 scores on scale Standard Error 0.712	3.73 scores on scale Standard Error 0.707	5.77 scores on scale Standard Error 0.724
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Change From BL II at Week 20	1.86 scores on scale Standard Error 0.653	3.18 scores on scale Standard Error 0.675	3.34 scores on scale Standard Error 0.673	5.95 scores on scale Standard Error 0.699
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Change From BL II at Week 24	2.19 scores on scale Standard Error 0.707	3.16 scores on scale Standard Error 0.730	3.78 scores on scale Standard Error 0.733	5.69 scores on scale Standard Error 0.765
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Change From BL II at Week 28	2.72 scores on scale Standard Error 0.699	3.20 scores on scale Standard Error 0.726	3.18 scores on scale Standard Error 0.730	5.07 scores on scale Standard Error 0.774
Change From Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score Change From BL II at Week 32	2.58 scores on scale Standard Error 0.784	2.97 scores on scale Standard Error 0.815	3.46 scores on scale Standard Error 0.815	6.55 scores on scale Standard Error 0.858

SECONDARY outcome

Timeframe: Double-blind Baseline (BL) II and Double-blind Period: Weeks 2, 4, 8, 12, 16, 20, 24, 28, and 32

The CGI-S is a 7-point scale that requires the clinician to rate the severity of the participant's illness at the time of assessment, relative to the clinician's past experience with participant who have the same diagnosis. Considering total clinical experience, a participant was assessed on severity of mental illness on the following scale: 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=extremely ill. Baseline II is defined as the last non-missing observation prior to the first dose of double-blind study drug. MMRM was used for analyses.

Outcome measures

Outcome measures
Measure	Double-blind: Vortioxetine 10 mg n=145 Participants Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 10 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.	Double-blind: Vortioxetine 20 mg n=144 Participants Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 20 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.	Double-blind: Vortioxetine 5 mg n=140 Participants Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 5 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.	Double-blind: Placebo n=151 Participants Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine placebo-matching capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Change From Baseline in Clinical Global Impression Scale-Severity (CGI-S) Score at Each Week Assessed Change From BL II at Week 2	0.26 scores on scale Standard Error 0.067	0.27 scores on scale Standard Error 0.068	0.32 scores on scale Standard Error 0.069	0.35 scores on scale Standard Error 0.065
Change From Baseline in Clinical Global Impression Scale-Severity (CGI-S) Score at Each Week Assessed Change From BL II at Week 4	0.30 scores on scale Standard Error 0.076	0.25 scores on scale Standard Error 0.078	0.32 scores on scale Standard Error 0.078	0.61 scores on scale Standard Error 0.075
Change From Baseline in Clinical Global Impression Scale-Severity (CGI-S) Score at Each Week Assessed Change From BL II at Week 8	0.29 scores on scale Standard Error 0.089	0.30 scores on scale Standard Error 0.093	0.38 scores on scale Standard Error 0.092	0.68 scores on scale Standard Error 0.091
Change From Baseline in Clinical Global Impression Scale-Severity (CGI-S) Score at Each Week Assessed Change From BL II at Week 12	0.24 scores on scale Standard Error 0.089	0.35 scores on scale Standard Error 0.092	0.46 scores on scale Standard Error 0.091	0.74 scores on scale Standard Error 0.092
Change From Baseline in Clinical Global Impression Scale-Severity (CGI-S) Score at Each Week Assessed Change From BL II at Week 16	0.25 scores on scale Standard Error 0.088	0.34 scores on scale Standard Error 0.091	0.50 scores on scale Standard Error 0.091	0.62 scores on scale Standard Error 0.094
Change From Baseline in Clinical Global Impression Scale-Severity (CGI-S) Score at Each Week Assessed Change From BL II at Week 20	0.17 scores on scale Standard Error 0.086	0.28 scores on scale Standard Error 0.089	0.40 scores on scale Standard Error 0.089	0.61 scores on scale Standard Error 0.094
Change From Baseline in Clinical Global Impression Scale-Severity (CGI-S) Score at Each Week Assessed Change From BL II at Week 24	0.24 scores on scale Standard Error 0.094	0.37 scores on scale Standard Error 0.097	0.45 scores on scale Standard Error 0.098	0.60 scores on scale Standard Error 0.103
Change From Baseline in Clinical Global Impression Scale-Severity (CGI-S) Score at Each Week Assessed Change From BL II at Week 28	0.30 scores on scale Standard Error 0.090	0.34 scores on scale Standard Error 0.093	0.33 scores on scale Standard Error 0.094	0.45 scores on scale Standard Error 0.101
Change From Baseline in Clinical Global Impression Scale-Severity (CGI-S) Score at Each Week Assessed Change From BL II at Week 32	0.26 scores on scale Standard Error 0.097	0.22 scores on scale Standard Error 0.100	0.41 scores on scale Standard Error 0.101	0.59 scores on scale Standard Error 0.108

SECONDARY outcome

Timeframe: Week 32

Population: FAS included all participants who were randomized in the double-blind period and received at least 1 dose of double-blind study drug. Overall number of participants analyzed is the number of participants with data available for analyses.

The CGI-I scale assesses the participant's improvement (or worsening) as assessed by the clinician relative to Baseline on a 7-point scale where 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse.

Outcome measures

Outcome measures
Measure	Double-blind: Vortioxetine 10 mg n=126 Participants Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 10 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.	Double-blind: Vortioxetine 20 mg n=144 Participants Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 20 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.	Double-blind: Vortioxetine 5 mg n=120 Participants Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 5 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.	Double-blind: Placebo n=119 Participants Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine placebo-matching capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Clinical Global Impression Scale-Global Improvement Scale (CGI-I) Score	3.5 scores on scale Standard Deviation 1.72	3.7 scores on scale Standard Deviation 1.56	3.9 scores on scale Standard Deviation 1.51	4.4 scores on scale Standard Deviation 1.47

SECONDARY outcome

Timeframe: From date of double-blind randomization (Week 16) up to relapse or 32 weeks of Double-blind Period which occurs first (Up to Week 44)

Population: FAS included all participants who were randomized in the double-blind period and received at least 1 dose of double-blind study drug.

Relapse was defined as either 1) MADRS Score ≥22, 2) lack of efficacy as determined by the investigator or 3) other unsatisfactory treatment response judged by the investigator. Time to relapse was defined as date of relapse - date of randomization + 1 (where date of relapse is the date of last dose, or date of last contact if date of last dose is missing, for participant with a relapse). Participants without relapse were censored. MADRS is a 10-item clinician rated scale to measure overall severity of depressive symptoms (i.e., apparent sadness, reported sadness, inner tension, etc.) rated on a 7-point Likert scale from 0 (normal) to 6 (most abnormal) with a total score ranges from 0 to 60. Higher scores indicate greater severity of symptoms. The IQR was 25th percentile to 75th percentile.

Outcome measures

Outcome measures
Measure	Double-blind: Vortioxetine 10 mg n=145 Participants Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 10 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.	Double-blind: Vortioxetine 20 mg n=144 Participants Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 20 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.	Double-blind: Vortioxetine 5 mg n=140 Participants Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 5 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.	Double-blind: Placebo n=151 Participants Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine placebo-matching capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Time From Randomization to Relapse of Major Depressive Disorder During the Entire 32-Week Double-Blind Treatment Period	NA weeks Interval 32.0 to Median and upper limit of IQR was not reached due to low number of participants with events.	NA weeks Interval 32.0 to Median and upper limit of IQR was not reached due to low number of participants with events.	NA weeks Interval 32.0 to Median and upper limit of IQR was not reached due to low number of participants with events.	NA weeks Interval 12.0 to Median and upper limit of IQR was not reached due to low number of participants with events.

Adverse Events

Open-label: Vortioxetine 10 mg

Serious events: 9 serious events

Other events: 417 other events

Deaths: 0 deaths

Double-blind: Placebo

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

Double-blind: Vortioxetine 5 mg

Serious events: 3 serious events

Other events: 30 other events

Deaths: 0 deaths

Double-blind: Vortioxetine 10 mg

Serious events: 4 serious events

Other events: 27 other events

Deaths: 1 deaths

Double-blind: Vortioxetine 20 mg

Serious events: 0 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Open-label: Vortioxetine 10 mg n=1106 participants at risk Vortioxetine 10 mg, capsules, orally, once, daily (QD) up to 8 weeks. Participants who achieved response (defined as a ≥50% reduction in Montgomery Asberg Depression Rating Scale (MADRS) total score from Baseline) continued to receive vortioxetine 10 mg, capsules, orally, QD for up to Week 16 (stabilization period) in the Open-label Period.	Double-blind: Placebo n=151 participants at risk Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine placebo-matching capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.	Double-blind: Vortioxetine 5 mg n=140 participants at risk Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 5 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.	Double-blind: Vortioxetine 10 mg n=145 participants at risk Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 10 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.	Double-blind: Vortioxetine 20 mg n=144 participants at risk Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 20 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Cardiac disorders Cardiac failure	0.00% 0/1106 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.66% 1/151 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/140 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/145 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/144 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Ear and labyrinth disorders Vertigo	0.00% 0/1106 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/151 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.71% 1/140 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/145 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/144 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Post procedural cellulitis	0.00% 0/1106 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/151 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/140 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.69% 1/145 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/144 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Pyelonephritis	0.00% 0/1106 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/151 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/140 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.69% 1/145 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/144 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Ankle fracture	0.00% 0/1106 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/151 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.71% 1/140 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/145 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/144 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Intraductal proliferative breast lesion	0.00% 0/1106 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/151 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.71% 1/140 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/145 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/144 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Completed suicide	0.00% 0/1106 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/151 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/140 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.69% 1/145 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/144 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Renal and urinary disorders Nephrolithiasis	0.00% 0/1106 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/151 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/140 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.69% 1/145 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/144 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Abdominal pain upper	0.09% 1/1106 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/151 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/140 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/145 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/144 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Hepatobiliary disorders Cholecystitis acute	0.09% 1/1106 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/151 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/140 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/145 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/144 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Appendicitis	0.09% 1/1106 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/151 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/140 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/145 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/144 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Injury, poisoning and procedural complications Hand fracture	0.09% 1/1106 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/151 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/140 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/145 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/144 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.09% 1/1106 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/151 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/140 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/145 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/144 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Pregnancy, puerperium and perinatal conditions Abortion missed	0.09% 1/1106 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/151 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/140 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/145 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/144 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Suicidal ideation	0.18% 2/1106 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/151 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/140 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/145 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/144 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Psychiatric disorders Panic attack	0.09% 1/1106 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/151 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/140 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/145 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/144 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Other adverse events

Other adverse events
Measure	Open-label: Vortioxetine 10 mg n=1106 participants at risk Vortioxetine 10 mg, capsules, orally, once, daily (QD) up to 8 weeks. Participants who achieved response (defined as a ≥50% reduction in Montgomery Asberg Depression Rating Scale (MADRS) total score from Baseline) continued to receive vortioxetine 10 mg, capsules, orally, QD for up to Week 16 (stabilization period) in the Open-label Period.	Double-blind: Placebo n=151 participants at risk Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine placebo-matching capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.	Double-blind: Vortioxetine 5 mg n=140 participants at risk Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 5 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.	Double-blind: Vortioxetine 10 mg n=145 participants at risk Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 10 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.	Double-blind: Vortioxetine 20 mg n=144 participants at risk Following Open-label Period, participants who achieved remission criteria (defined as MADRS total score ≤12 at Weeks 14 and 16) were randomized to receive vortioxetine 20 mg, capsules, orally, QD from Week 17 up to Week 44 in the Double-blind Period.
Infections and infestations Upper respiratory tract infection	0.00% 0/1106 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.0% 6/151 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.4% 9/140 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.2% 9/145 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	6.2% 9/144 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Infections and infestations Nasopharyngitis	5.1% 56/1106 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.6% 4/151 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.0% 7/140 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.8% 7/145 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.6% 8/144 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Nausea	26.4% 292/1106 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.3% 2/151 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.9% 4/140 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	3.4% 5/145 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	9.0% 13/144 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Investigations Weight increased	0.00% 0/1106 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	2.0% 3/151 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	3.6% 5/140 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	4.8% 7/145 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.6% 8/144 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/1106 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.3% 2/151 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	5.7% 8/140 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/145 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	1.4% 2/144 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Nervous system disorders Headache	8.2% 91/1106 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/151 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/140 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/145 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/144 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.
Gastrointestinal disorders Dry mouth	5.2% 58/1106 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/151 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/140 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/145 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.	0.00% 0/144 • From first dose of study drug and up to 30 days after the last dose (Up to 48 weeks) At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER