The Relationship Among Changes in Brain Network Activation in Adult Outpatients With Major Depressive Disorder

• Sponsor: Rush University Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT02749721
• Collaborator: Takeda Pharmaceuticals North America, Inc. (Industry), ElMindA Ltd (Industry)
• Enrollment: 31
• Locations: 2
• Arm: 1
• Actual Duration (Months): 26
• Patients Per Site: 15.5
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

The purpose of this study is to explore patterns of Brain Network Activation (BNA) changes from baseline to endpoint on 1) efficacy of core symptoms of Major Depressive Disorder (MDD) and 2) improvement of cognitive dysfunction with acute treatment with flexible dose vortioxetine in adult outpatients with MDD and subjective complaints of cognitive dysfunction.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: vortioxetine	Phase 4

Detailed Description

Vortioxetine is a novel antidepressant with hypothetical multimodal mechanism of action. It is thought to work through a combination of multiple pharmacological modes of action: 5-HT (hydroxytryptamine, or serotonin) reuptake inhibition, 5-HT3 (hydroxytryptamine, or serotonin) and 5-HT7 (hydroxytryptamine, or serotonin) receptor antagonism, 5-HT1A (hydroxytryptamine, or serotonin) receptor agonism, and 5-HT1B (hydroxytryptamine, or serotonin) receptor partial agonism. In vivo nonclinical studies have demonstrated that vortioxetine enhances levels of the neurotransmitters 5-HT (hydroxytryptamine, or serotonin), norepinephrine (NE), dopamine (DA), acetylcholine and histamine in specific areas of the brain. These affinities are all considered to be of clinical relevance and involved in the mechanism of action at therapeutic doses.

Vortioxetine has been shown to improve core depressive symptoms and improve cognitive function in adult outpatients with MDD and subjective complaints of cognitive function. This pilot study is intended to evaluate the extent to which BNA technology can provide clinically valuable information and provide information toward designing a subsequent confirmatory study that will further elucidate the effect of vortioxetine on MDD and cognitive function in this population. This exploratory study will ascertain the acute changes in core depression symptoms, cognitive function, tolerability, and safety using flexible-dose vortioxetine in adult outpatients with MDD with subjective complaints of cognitive functioning, as measured by BNA changes and standard outcome measures for depression and cognition.

The study consists of 8 weeks of open-label treatment for MDD with response to treatment measured by standard research depression scales and BNA electroencephalogram (EEG) readings taken at certain points during the trial. An important aim in this study is to explore what correlations may exist between changes in measured brainwave patterns and reported change in depressive symptoms

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Relationship Among Changes in Brain Network Activation, Changes in Core Depressive and Cognitive Symptoms and Safety and Tolerability in Adults With Major Depressive Disorder Treated With Open-Label, Flexible-Dose Vortioxetine
• Actual Study Start Date: Dec 1, 2016
• Actual Primary Completion Date: Jan 31, 2019
• Actual Study Completion Date: Jan 31, 2019

Arms and Interventions

Arm	Intervention/Treatment
Other: Other - vortioxetine Open-label vortioxetine	Drug: vortioxetine; Open-label vortioxetine

Outcome Measures

Primary Outcome Measures

1. Change in Montgomery and Asberg Depression Rating Scale (MADRS) [from baseline to endpoint (up to 8 weeks)]

   The MADRS is a 10-item rating scale designed to assess the severity of symptoms of depression. Range is 0-60. Higher score means more severe.

2. Change From Baseline to Endpoint in Digital Symbol Substitution Test. [Baseline to endpoint (week 8)]

   Change in cognitive function defined as change from baseline to endpoint. The Digital Symbol Substitution Test (DSST) is a cognitive test designed to assess psychomotor speed of performance requiring visual perception, spatial decision-making and motor skills. The DSST consists of 133 digits and requires the subject to substitute each digit with a simple symbol in a 90-second period. The number of correct symbols within the allowed time (eg, 90 sec) is measured. It takes approximately 5 minutes to complete and score the DSST.

3. BNA Scores Amplitudes [Baseline to Endpoint (8 weeks)]

   Brain Network Analytics (BNA) is a tool intended for the post-hoc statistical analysis of the human EEG, utilizing both resting-state EEG and event-related potentials (ERP) waveforms. The BNA algorithm compares a patient's ERP amplitudes and latencies to those of a large group of healthy, age-matched subjects in order to visualize and quantify changes in specific brain functions. The BNA algorithm was used to detect subjects' P200 and P300 ERP components from EEG data recorded during the AOB and VGNG tasks. BNA scores represent these ERP components in terms of amplitude (in microvolts) and latency (in milliseconds).

4. BNA Scores Latencies [Baseline to Endpoint (8 weeks)]

   Brain Network Analytics (BNA) is a tool intended for the post-hoc statistical analysis of the human EEG, utilizing both resting-state EEG and event-related potentials (ERP) waveforms. The BNA algorithm compares a patient's ERP amplitudes and latencies to those of a large group of healthy, age-matched subjects in order to visualize and quantify changes in specific brain functions. The BNA algorithm was used to detect subjects' P200 and P300 ERP components from EEG data recorded during the AOB and VGNG tasks. BNA scores represent these ERP components in terms of amplitude (in microvolts) and latency (in milliseconds).

Secondary Outcome Measures

1. Changes in Hamilton Depression Rating Scale (HDRS) 17 From Baseline to 8 Week Endpoint [Baseline to endpoint (week 8)]

   The HDRS is a clinician-rated used to rate the patient's depressive state. The 17 question version of the scale rates depressive state based on feelings of depression, guilt, suicidality, anxiety, agitation, somatic symptoms, level of insight, patterns of insomnia, loss of interest in work and other activities, weight loss, and hypochondriasis. Additionally, the 28 question version rates depersonalization, paranoia, obsessions/compulsions, hypersomnia, appetite increase, and psychomotor slowing. The total score is obtained by summing the score of each item, 0-4 (symptom is absent, mild, moderate, or severe) or 0-2 (absent, slight or trivial, clearly present). Scores can range from 0 to 54 for the 17 question version and 0 to 83 for the 28 question version. Scores between 0 and 6 do not indicate the presence of depression, scores between 7 and 17 indicate mild depression, scores between 18 and 24 indicate moderate depression, and scores over 24 indicate severe depression.

2. Changes in Hamilton Depression Rating Scale (HDRS) 28 From Baseline to 8 Week Endpoint [Baseline to endpoint (week 8)]

   The HDRS is a clinician-rated used to rate the patient's depressive state. The 17 question version of the scale rates depressive state based on feelings of depression, guilt, suicidality, anxiety, agitation, somatic symptoms, level of insight, patterns of insomnia, loss of interest in work and other activities, weight loss, and hypochondriasis. Additionally, the 28 question version rates depersonalization, paranoia, obsessions/compulsions, hypersomnia, appetite increase, and psychomotor slowing. The total score is obtained by summing the score of each item, 0-4 (symptom is absent, mild, moderate, or severe) or 0-2 (absent, slight or trivial, clearly present). Scores can range from 0 to 54 for the 17 question version and 0 to 83 for the 28 question version. Scores between 0 and 6 do not indicate the presence of depression, scores between 7 and 17 indicate mild depression, scores between 18 and 24 indicate moderate depression, and scores over 24 indicate severe depression.

3. Changes in Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-16-SR) From Baseline to 8 Week Endpoint [Baseline to endpoint (week 8)]

   The QIDS-16-SR is a 16-item self-rated assessment of the severity of depressive symptoms. The assessments can be used to screen for depression, although they have been used predominantly as measures of symptom severity. The nine domains comprise 1) sad mood; 2) concentration; 3) self-criticism; 4) suicidal ideation; 5) interest; 6) energy/fatigue; 7) sleep disturbance (initial, middle, and late insomnia or hypersomnia); 8) decrease or increase in appetite or weight; and 9) psychomotor agitation or retardation. The total score ranges from 0 to 27 with higher scores equating to more severe symptomatology. The seven day period prior to assessment is the usual time frame for assessing symptom severity.

4. Changes in Clinical Global Impression Scale (CGI-S) From Baseline to 8 Week Endpoint [Baseline to endpoint (week 8)]

   The CGI-S assesses the clinician's impression of the subject's current mental illness state (considering their total clinical experience with this particular population) via 7 point scale (ranging from 1-7) with higher scores equating to more symptoms. For example, a score of 1 = normal, not at all ill and a score of 7 = severely ill.

5. Correlations Between BNA Amplitude Scores and Clinical, Cognitive, and Functionality Assessments Using Baseline Scores [Baseline to Endpoint (8 weeks)]

   Pearson correlation was used to examine the associations between baseline BNA amplitude scores and outcomes including measures of MDD symptoms, cognitive function and functionality.

6. Correlations Between BNA Latency Scores and Clinical, Cognitive, and Functionality Assessments Using Baseline Scores [Baseline to Endpoint (8 weeks)]

   Pearson correlation was used to examine the associations between baseline BNA latency scores and outcomes including measures of MDD symptoms, cognitive function and functionality.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• The subject has single episode or recurrent MDD (acute onset of recurrence of recurrent MDD with poor inter-episode recovery) (inter-episode periods cannot meet full MDD criteria) as the primary diagnosis according to DSM-IV-TR criteria. The current major depressive episode (MDE) will be confirmed using the Mini International Neuropsychiatric Interview (MINI V6.0.0).

• The subject has a MADRS total score ≥26.

• Subject reports subjective cognitive dysfunction (such as difficulty concentrating, slow thinking, and difficulty in learning new things or remembering things).

• The reported duration of the current MDE is at least 3 months and no longer than 24 months.

• The subject is a man or woman between 18 and 65 years old, inclusive.

• Right-handed, normal (corrected) vision, and normal hearing.

Exclusion Criteria:

• The subject has a score of ≥70 on the Digit Symbol Substitution Test (DSST) at the Baseline Visit.

• Failure to respond to or inability to tolerate an adequate trial of vortioxetine in the past.

• Exposure to an investigational compound 30 days prior to enrollment

• Exposure to any psychoactive or otherwise excluded medication within five half-lives of the baseline visit or during the study. Excluded medications include: antidepressants, anxiolytics, anticonvulsants, barbiturates, chloral hydrate, lithium, antipsychotics, benzodiazepines, hypnotics, monoamine oxidase inhibitors (MAOIs), muscle relaxers, triptans, centrally-acting antihistamines, central alpha-2 agonists, decongestants, psychostimulants, dopamine agonists, opioid pain medications, oral corticosteroids, L-methylfolate, S-adenosyl methionine (SAMe), 5-HTP (hydroxytryptophan), St. John's Wort,

• The subject has 1 or more of the following:

• Primary psychiatric disorder other than MDD as defined in the Diagnostic and Statistical Manual of Mental Disorders 4 Text Revision (DSM-IV-TR) (as assessed by the MINI, Version 6.0.0).

• Current or history of attention deficit hyperactivity disorder (ADHD), pervasive developmental disorder, manic or hypomanic episode, schizophrenia, or any other psychotic disorder, including major depression with psychotic features, mental retardation, organic mental disorders, or mental disorders due to a general medical condition as defined in the DSM-IV-TR.

• Current diagnosis of alcohol or other substance abuse or dependence (excluding nicotine or caffeine) as defined in the DSM-IV-TR that has not been in sustained full remission for at least 6 months (for abuse) and 12 months (for dependence) prior to Screening.

• Positive urine drug screen prior to Baseline.

• Presence or history of a clinically significant neurological disorder (including epilepsy).

• Neurodegenerative disorder (Alzheimer Disease, Parkinson Disease, multiple sclerosis, Huntington Disease, etc).

• Any unstable medical condition as determined by the principal investigator (PI).

• Any DSM-IV Axis II disorder that might compromise the study as determined by the PI.

• The subject has any other disorder for which the treatment takes priority over treatment of MDD or is likely to interfere with study treatment or impair treatment compliance.

• The subject has physical, cognitive, or language impairment of such severity as to adversely affect the validity of the data derived from the neuropsychological tests.

• The subject has a significant risk of suicide according to the PI's clinical judgment.

• The subject, in the opinion of the PI, poses a risk of harm to others.

• The subject has initiated formal cognitive or behavioral therapy, systemic psychotherapy within less than 6 months of study screening, or has plans to initiate such therapy during the study.

• The subject has received electroconvulsive therapy, vagus nerve stimulation, or repetitive transcranial magnetic stimulation within 12 months prior to Screening.

• The current MDE is considered by the PI to have been resistant to 2 adequate antidepressant treatments of at least 6 weeks duration each at the recommended dose.

• The subject is pregnant or breastfeeding, or is intending to become pregnant before, during, or within 30 days after participating in this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rush University Medical Center	Chicago	Illinois	United States	60612
2	Rush University Medical Center	Skokie	Illinois	United States	60076

Sponsors and Collaborators

• Rush University Medical Center
• Takeda Pharmaceuticals North America, Inc.
• ElMindA Ltd

Investigators

• Principal Investigator: John M Zajecka, MD, Rush University Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 16, 2017
• Informed Consent Form: Consent version 08-29-16 IRB APPROVED - Aug 29, 2016
• Informed Consent Form: onsent version 08-29-16 IRB APPROVED for 2017 - Apr 26, 2017
• Informed Consent Form: consent version 04-09-18 IRB APPROVED - Apr 9, 2018

More Information

Publications

None provided.

• Responsible Party: Rush University Medical Center
• ClinicalTrials.gov Identifier: NCT02749721
• Other Study ID Numbers: IISR-2014-100702a; NCT02559947
• First Posted: Apr 25, 2016
• Last Update Posted: Oct 4, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Rush University Medical Center: depression; brain network activation; vortioxetine
• Additional relevant MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major; Vortioxetine

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from several sources, including referrals, advertisements and following completion of another clinical trial.
Pre-assignment Detail	Participants were screened over a 1-2 week period to assess inclusion/exclusion criteria (i.e., to obtain lab results, to ensure adequate washout of any prohibited concomitant medications, etc).

Arm/Group Title	Vortioxetine
Arm/Group Description	vortioxetine 5-20 mg/day
Period Title: Screening
STARTED	31
COMPLETED	25
NOT COMPLETED	6
Period Title: Screening
STARTED	25
COMPLETED	22
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Vortioxetine
Arm/Group Description	vortioxetine 5-20 mg/day
Overall Participants	25
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	25 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	15 60%
Male	10 40%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 12%
Not Hispanic or Latino	22 88%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	2 8%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	6 24%
White	17 68%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	25 100%
Major Depressive Disorder-single or recurrent (participants) [Number]
Recurrent episode	19 76%
Single episode	6 24%

Outcome Measures

1. Primary Outcome

Title	Change in Montgomery and Asberg Depression Rating Scale (MADRS)
Description	The MADRS is a 10-item rating scale designed to assess the severity of symptoms of depression. Range is 0-60. Higher score means more severe.
Time Frame	from baseline to endpoint (up to 8 weeks)

Outcome Measure Data

Analysis Population Description

25 subjects were included in the baseline analysis, and 22 subjects completed all visits and were included in subsequent analyses

Arm/Group Title	Vortioxetine
Arm/Group Description	vortioxetine 5-20 mg/day
Measure Participants	25
Baseline	33.28
Week 8	16.23

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Paired t-test
	Comments

2. Primary Outcome

Title	Change From Baseline to Endpoint in Digital Symbol Substitution Test.
Description	Change in cognitive function defined as change from baseline to endpoint. The Digital Symbol Substitution Test (DSST) is a cognitive test designed to assess psychomotor speed of performance requiring visual perception, spatial decision-making and motor skills. The DSST consists of 133 digits and requires the subject to substitute each digit with a simple symbol in a 90-second period. The number of correct symbols within the allowed time (eg, 90 sec) is measured. It takes approximately 5 minutes to complete and score the DSST.
Time Frame	Baseline to endpoint (week 8)

Outcome Measure Data

Analysis Population Description

25 subjects were included in the baseline analysis, and 22 subjects completed all visits and were included in subsequent analyses

Arm/Group Title	Vortioxetine
Arm/Group Description	vortioxetine 5-20 mg/day
Measure Participants	25
Baseline	48.24
Endpoint (week 8)	55.55

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments
	Method	Paired t-test
	Comments

3. Primary Outcome

Title	BNA Scores Amplitudes
Description	Brain Network Analytics (BNA) is a tool intended for the post-hoc statistical analysis of the human EEG, utilizing both resting-state EEG and event-related potentials (ERP) waveforms. The BNA algorithm compares a patient's ERP amplitudes and latencies to those of a large group of healthy, age-matched subjects in order to visualize and quantify changes in specific brain functions. The BNA algorithm was used to detect subjects' P200 and P300 ERP components from EEG data recorded during the AOB and VGNG tasks. BNA scores represent these ERP components in terms of amplitude (in microvolts) and latency (in milliseconds).
Time Frame	Baseline to Endpoint (8 weeks)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vortioxetine
Arm/Group Description	vortioxetine 5-20 mg/day
Measure Participants	25
AOB P200 amplitude Baseline	4.04 (2.60)
AOB P200 amplitude Endpoint (8 weeks)	3.96 (2.31)
AOB P3a amplitude Baseline	9.43 (5.00)
AOB P3a amplitude Endpoint (8 weeks)	7.13 (4.10)
AOB P3b amplitude Baseline	6.48 (3.69)
AOB P3b amplitude Endpoint (8 weeks)	6.75 (4.30)
VGNG P200 amplitude Baseline	3.40 (1.37)
VGNG P200 amplitude Endpoint (8 weeks)	3.66 (1.53)
VGNG P3a amplitude Baseline	3.33 (1.60)
VGNG P3a amplitude Endpoint (8 weeks)	3.55 (1.77)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between MADRS and AOB P200 (amplitude) baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.610
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.125
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between MADRS and AOB P3a (amplitude) baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.288
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.294
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between MADRS and AOB P3b (amplitude) baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.134
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.405
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between MADRS and VGNG P200 (amplitude) baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.083
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.397
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between MADRS and VGNG P3a (amplitude) baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.034
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.476
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between DSST and AOB P200 baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.031
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.509
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between DSST and AOB P3a (amplitude) baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.500
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.197
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between DSST and AOB P3b baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.185
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.376
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between DSST and VGNG P200 baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.659
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.108
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between DSST and VGNG P3a baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.611
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.125
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P200 (amplitude) and MADRS (baseline to endpoint percent change)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.671
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.111
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3a (amplitude) and MADRS (baseline to endpoint percent change)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.931
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.026
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3b (amplitude) and MADRS (baseline to endpoint percent change)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.155
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.516
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P200 (amplitude) and MADRS (baseline to endpoint percent change)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.297
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.268
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P3a (amplitude) and MADRS (baseline to endpoint percent change)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.494
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.184
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P200 (amplitude) and DSST (baseline to endpoint percent change)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.811
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.065
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3a (amplitude) and DSST (baseline to endpoint percent change)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.877
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.048
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3b (amplitude) and DSST (baseline to endpoint percent change)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.557
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.246
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P200 (amplitude) and DSST (baseline to endpoint percent change)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.500
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.182
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P3a (amplitude) and DSST (baseline to endpoint percent change)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.297
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.288
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	A comparison between vortioxetine arm patients' and healthy controls' AOB P200 amplitudes at baseline. The healthy control group subjects have been previously documented in NCT02418208 (Clinical trials of the Rockies, Inc. Denver, Colorado, US and Clinical Research Center of Nevada Las Vegas, Nevada, US ) and in NCT02875496 (The Villages Health, The Villages, Florida, US).
	Type of Statistical Test	Other
	Comments	Differences in BNA scores between MDD and healthy subjects were analyzed for baseline visits using an ANCOVA model with group as a factor, and age as a covariate.
Statistical Test of Hypothesis	p-Value	0.575
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	F statistic
	Estimated Value	0.318
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	A comparison between vortioxetine arm patients' and healthy controls' AOB P200 amplitudes at Endpoint. The healthy control group subjects have been previously documented in NCT02418208 (Clinical trials of the Rockies, Inc. Denver, Colorado, US and Clinical Research Center of Nevada Las Vegas, Nevada, US ) and in NCT02875496 (The Villages Health, The Villages, Florida, US).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.541
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	F statistic
	Estimated Value	0.378
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	A comparison between vortioxetine arm patients' and healthy controls' AOB P3a amplitudes at baseline. The healthy control group subjects have been previously documented in NCT02418208 (Clinical trials of the Rockies, Inc. Denver, Colorado, US and Clinical Research Center of Nevada Las Vegas, Nevada, US ) and in NCT02875496 (The Villages Health, The Villages, Florida, US).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.912
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	F
	Estimated Value	0.012
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	A comparison between vortioxetine arm patients' and healthy controls' AOB P3a amplitudes at Endpoint. The healthy control group subjects have been previously documented in NCT02418208 (Clinical trials of the Rockies, Inc. Denver, Colorado, US and Clinical Research Center of Nevada Las Vegas, Nevada, US ) and in NCT02875496 (The Villages Health, The Villages, Florida, US).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.214
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	F statistic
	Estimated Value	1.586
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	A comparison between vortioxetine arm patients' and healthy controls' AOB P3b amplitudes at baseline. The healthy control group subjects have been previously documented in NCT02418208 (Clinical trials of the Rockies, Inc. Denver, Colorado, US and Clinical Research Center of Nevada Las Vegas, Nevada, US ) and in NCT02875496 (The Villages Health, The Villages, Florida, US).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.504
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	F statistic
	Estimated Value	0.453
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	A comparison between vortioxetine arm patients' and healthy controls' AOB P3b amplitudes at Endpoint. The healthy control group subjects have been previously documented in NCT02418208 (Clinical trials of the Rockies, Inc. Denver, Colorado, US and Clinical Research Center of Nevada Las Vegas, Nevada, US ) and in NCT02875496 (The Villages Health, The Villages, Florida, US).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.546
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	F statistic
	Estimated Value	0.37
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	A comparison between vortioxetine arm patients' and healthy controls' VGNG P200 amplitudes at baseline. The healthy control group subjects have been previously documented in NCT02418208 (Clinical trials of the Rockies, Inc. Denver, Colorado, US and Clinical Research Center of Nevada Las Vegas, Nevada, US ) and in NCT02875496 (The Villages Health, The Villages, Florida, US).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.895
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	F statistic
	Estimated Value	0.017
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	A comparison between vortioxetine arm patients' and healthy controls' VGNG P200 amplitudes at Endpoint. The healthy control group subjects have been previously documented in NCT02418208 (Clinical trials of the Rockies, Inc. Denver, Colorado, US and Clinical Research Center of Nevada Las Vegas, Nevada, US ) and in NCT02875496 (The Villages Health, The Villages, Florida, US).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.673
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	F statistic
	Estimated Value	0.179
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	A comparison between vortioxetine arm patients' and healthy controls' VGNG P3a amplitudes at baseline. The healthy control group subjects have been previously documented in NCT02418208 (Clinical trials of the Rockies, Inc. Denver, Colorado, US and Clinical Research Center of Nevada Las Vegas, Nevada, US ) and in NCT02875496 (The Villages Health, The Villages, Florida, US).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.27
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	F statistic
	Estimated Value	1.241
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	A comparison between vortioxetine arm patients' and healthy controls' VGNG P3a amplitudes at Endpoint. The healthy control group subjects have been previously documented in NCT02418208 (Clinical trials of the Rockies, Inc. Denver, Colorado, US and Clinical Research Center of Nevada Las Vegas, Nevada, US ) and in NCT02875496 (The Villages Health, The Villages, Florida, US).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.837
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	F statistic
	Estimated Value	0.042
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Primary Outcome

Title	BNA Scores Latencies
Description	Brain Network Analytics (BNA) is a tool intended for the post-hoc statistical analysis of the human EEG, utilizing both resting-state EEG and event-related potentials (ERP) waveforms. The BNA algorithm compares a patient's ERP amplitudes and latencies to those of a large group of healthy, age-matched subjects in order to visualize and quantify changes in specific brain functions. The BNA algorithm was used to detect subjects' P200 and P300 ERP components from EEG data recorded during the AOB and VGNG tasks. BNA scores represent these ERP components in terms of amplitude (in microvolts) and latency (in milliseconds).
Time Frame	Baseline to Endpoint (8 weeks)

Outcome Measure Data

Analysis Population Description

These correlation analyses were done only on participants in the vortioxetine arm and did not include the group of healthy controls

Arm/Group Title	Vortioxetine
Arm/Group Description	vortioxetine 5-20 mg/day
Measure Participants	25
AOB P200 latency Baseline	177.37 (12.66)
AOB P200 latency Endpoint (8 weeks)	177.90 (14.12)
AOB P3a latency Baseline	308.47 (50.93)
AOB P3a latency Endpoint (8 weeks)	281.38 (40.63)
AOB P3b latency Baseline	370.07 (55.87)
AOB P3b latency Endpoint (8 weeks)	367.27 (37.59)
VGNG P200 latency Baseline	170.35 (14.05)
VGNG P200 latency Endpoint (8 weeks)	172.11 (16.35)
VGNG P3a latency Baseline	433.75 (24.91)
VGNG P3a latency Endpoint (8 weeks)	431.44 (32.36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between DSST and AOB P200 (Latency) baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.143
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.359
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between DSST and AOB P3b (latency) baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.500
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.197
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between DSST and AOB P3b (latency) baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.337
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.277
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between DSST and VGNG P200 (latency) baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.832
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.052
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between DSST and VGNG P3a (latency) baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.68
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.103
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between DSST and AOB P200 (Latency) baseline to endpoint percentage change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.777
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.074
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between DSST and AOB P3a (Latency) baseline to endpoint percentage change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.834
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.061
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between DSST and AOB P3b (Latency) baseline to endpoint percentage change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.988
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.006
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between DSST and VGNG P200 (Latency) baseline to endpoint percentage change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.788
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.073
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between DSST and VGNG P3a (Latency) baseline to endpoint percentage change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.168
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.375
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between MADRS and AOB P200 (Latency) baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.108
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.392
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between MADRS and AOB P3a (Latency) baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.124
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.415
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between MADRS and AOB P3b (Latency) baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.185
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.362
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between MADRS and VGNG P200 (Latency) baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.923
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.023
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between MADRS and VGNG P3a (Latency) baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.77
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.071
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between MADRS and AOB P200 (Latency) baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.712
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.097
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between MADRS and AOB P3a (Latency) baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.845
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.058
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between MADRS and AOB P3b (Latency) baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.616
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.194
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between MADRS and VGNG P200 (Latency) baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.323
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.255
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between MADRS and VGNG P3a (Latency) baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.473
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.193
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	A comparison between vortioxetine arm patients' and healthy controls' AOB P200 latencies at baseline. The healthy control group subjects have been previously documented in NCT02418208 (Clinical trials of the Rockies, Inc. Denver, Colorado, US and Clinical Research Center of Nevada Las Vegas, Nevada, US ) and in NCT02875496 (The Villages Health, The Villages, Florida, US).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.031
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	F statistic
	Estimated Value	4.909
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	A comparison between vortioxetine arm patients' and healthy controls' AOB P200 latencies at Endpoint. The healthy control group subjects have been previously documented in NCT02418208 (Clinical trials of the Rockies, Inc. Denver, Colorado, US and Clinical Research Center of Nevada Las Vegas, Nevada, US ) and in NCT02875496 (The Villages Health, The Villages, Florida, US).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.281
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	F statistic
	Estimated Value	1.189
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	A comparison between vortioxetine arm patients' and healthy controls' AOB P3a latencies at baseline. The healthy control group subjects have been previously documented in NCT02418208 (Clinical trials of the Rockies, Inc. Denver, Colorado, US and Clinical Research Center of Nevada Las Vegas, Nevada, US ) and in NCT02875496 (The Villages Health, The Villages, Florida, US).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.966
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	F statistic
	Estimated Value	0.001
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	A comparison between vortioxetine arm patients' and healthy controls' AOB P3a latencies at Endpoint. The healthy control group subjects have been previously documented in NCT02418208 (Clinical trials of the Rockies, Inc. Denver, Colorado, US and Clinical Research Center of Nevada Las Vegas, Nevada, US ) and in NCT02875496 (The Villages Health, The Villages, Florida, US).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.048
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	F statistic
	Estimated Value	4.121
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	A comparison between vortioxetine arm patients' and healthy controls' AOB P3b latencies at baseline. The healthy control group subjects have been previously documented in NCT02418208 (Clinical trials of the Rockies, Inc. Denver, Colorado, US and Clinical Research Center of Nevada Las Vegas, Nevada, US ) and in NCT02875496 (The Villages Health, The Villages, Florida, US).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	F statistic
	Estimated Value	8.573
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	A comparison between vortioxetine arm patients' and healthy controls' AOB P3b latencies at Endpoint. The healthy control group subjects have been previously documented in NCT02418208 (Clinical trials of the Rockies, Inc. Denver, Colorado, US and Clinical Research Center of Nevada Las Vegas, Nevada, US ) and in NCT02875496 (The Villages Health, The Villages, Florida, US).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.101
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	F statistic
	Estimated Value	2.823
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	A comparison between vortioxetine arm patients' and healthy controls' VGNG P200 latencies at baseline. The healthy control group subjects have been previously documented in NCT02418208 (Clinical trials of the Rockies, Inc. Denver, Colorado, US and Clinical Research Center of Nevada Las Vegas, Nevada, US ) and in NCT02875496 (The Villages Health, The Villages, Florida, US).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.373
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	F statistic
	Estimated Value	0.806
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	A comparison between vortioxetine arm patients' and healthy controls' VGNG P200 latencies at Endpoint. The healthy control group subjects have been previously documented in NCT02418208 (Clinical trials of the Rockies, Inc. Denver, Colorado, US and Clinical Research Center of Nevada Las Vegas, Nevada, US ) and in NCT02875496 (The Villages Health, The Villages, Florida, US).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.183
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	F statistic
	Estimated Value	1.822
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	A comparison between vortioxetine arm patients' and healthy controls' VGNG P3a latencies at baseline. The healthy control group subjects have been previously documented in NCT02418208 (Clinical trials of the Rockies, Inc. Denver, Colorado, US and Clinical Research Center of Nevada Las Vegas, Nevada, US ) and in NCT02875496 (The Villages Health, The Villages, Florida, US).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.475
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	F statistic
	Estimated Value	0.516
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	A comparison between vortioxetine arm patients' and healthy controls' VGNG P3a latencies at Endpoint. The healthy control group subjects have been previously documented in NCT02418208 (Clinical trials of the Rockies, Inc. Denver, Colorado, US and Clinical Research Center of Nevada Las Vegas, Nevada, US ) and in NCT02875496 (The Villages Health, The Villages, Florida, US).
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.645
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	F statistic
	Estimated Value	0.214
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Changes in Hamilton Depression Rating Scale (HDRS) 17 From Baseline to 8 Week Endpoint
Description	The HDRS is a clinician-rated used to rate the patient's depressive state. The 17 question version of the scale rates depressive state based on feelings of depression, guilt, suicidality, anxiety, agitation, somatic symptoms, level of insight, patterns of insomnia, loss of interest in work and other activities, weight loss, and hypochondriasis. Additionally, the 28 question version rates depersonalization, paranoia, obsessions/compulsions, hypersomnia, appetite increase, and psychomotor slowing. The total score is obtained by summing the score of each item, 0-4 (symptom is absent, mild, moderate, or severe) or 0-2 (absent, slight or trivial, clearly present). Scores can range from 0 to 54 for the 17 question version and 0 to 83 for the 28 question version. Scores between 0 and 6 do not indicate the presence of depression, scores between 7 and 17 indicate mild depression, scores between 18 and 24 indicate moderate depression, and scores over 24 indicate severe depression.
Time Frame	Baseline to endpoint (week 8)

Outcome Measure Data

Analysis Population Description

25 subjects were included in the baseline analysis, and 22 subjects completed all visits and were included in subsequent analyses

Arm/Group Title	Vortioxetine
Arm/Group Description	Open-label vortioxetine vortioxetine: Open-label vortioxetine
Measure Participants	25
Baseline	23.76
Endpoint (week 8)	11.59

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Paired t-test
	Comments

6. Secondary Outcome

Title	Changes in Hamilton Depression Rating Scale (HDRS) 28 From Baseline to 8 Week Endpoint
Description	The HDRS is a clinician-rated used to rate the patient's depressive state. The 17 question version of the scale rates depressive state based on feelings of depression, guilt, suicidality, anxiety, agitation, somatic symptoms, level of insight, patterns of insomnia, loss of interest in work and other activities, weight loss, and hypochondriasis. Additionally, the 28 question version rates depersonalization, paranoia, obsessions/compulsions, hypersomnia, appetite increase, and psychomotor slowing. The total score is obtained by summing the score of each item, 0-4 (symptom is absent, mild, moderate, or severe) or 0-2 (absent, slight or trivial, clearly present). Scores can range from 0 to 54 for the 17 question version and 0 to 83 for the 28 question version. Scores between 0 and 6 do not indicate the presence of depression, scores between 7 and 17 indicate mild depression, scores between 18 and 24 indicate moderate depression, and scores over 24 indicate severe depression.
Time Frame	Baseline to endpoint (week 8)

Outcome Measure Data

Analysis Population Description

25 subjects were included in the baseline analysis, and 22 subjects completed all visits and were included in subsequent analyses

Arm/Group Title	Vortioxetine
Arm/Group Description	Open-label vortioxetine: 5-20 mg
Measure Participants	25
Baseline	28.44
Endpoint (week 8)	14.77

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Paired t-test
	Comments

7. Secondary Outcome

Title	Changes in Quick Inventory of Depressive Symptomatology - Self-Report (QIDS-16-SR) From Baseline to 8 Week Endpoint
Description	The QIDS-16-SR is a 16-item self-rated assessment of the severity of depressive symptoms. The assessments can be used to screen for depression, although they have been used predominantly as measures of symptom severity. The nine domains comprise 1) sad mood; 2) concentration; 3) self-criticism; 4) suicidal ideation; 5) interest; 6) energy/fatigue; 7) sleep disturbance (initial, middle, and late insomnia or hypersomnia); 8) decrease or increase in appetite or weight; and 9) psychomotor agitation or retardation. The total score ranges from 0 to 27 with higher scores equating to more severe symptomatology. The seven day period prior to assessment is the usual time frame for assessing symptom severity.
Time Frame	Baseline to endpoint (week 8)

Outcome Measure Data

Analysis Population Description

25 subjects were included in the baseline analysis, and 22 subjects completed all visits and were included in subsequent analyses

Arm/Group Title	Vortioxetine
Arm/Group Description	Open-label vortioxetine: 5-20 mg
Measure Participants	25
Baseline	16.24
Endpoint (week 8)	7.91

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Paired t-test
	Comments

8. Secondary Outcome

Title	Changes in Clinical Global Impression Scale (CGI-S) From Baseline to 8 Week Endpoint
Description	The CGI-S assesses the clinician's impression of the subject's current mental illness state (considering their total clinical experience with this particular population) via 7 point scale (ranging from 1-7) with higher scores equating to more symptoms. For example, a score of 1 = normal, not at all ill and a score of 7 = severely ill.
Time Frame	Baseline to endpoint (week 8)

Outcome Measure Data

Analysis Population Description

25 subjects were included in the baseline analysis, and 22 subjects completed all visits and were included in subsequent analyses

Arm/Group Title	Vortioxetine
Arm/Group Description	Open-label vortioxetine: 5-20 mg
Measure Participants	25
Baseline	4.88
Endpoint (week 8)	2.64

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Paired t-test
	Comments

9. Secondary Outcome

Title	Correlations Between BNA Amplitude Scores and Clinical, Cognitive, and Functionality Assessments Using Baseline Scores
Description	Pearson correlation was used to examine the associations between baseline BNA amplitude scores and outcomes including measures of MDD symptoms, cognitive function and functionality.
Time Frame	Baseline to Endpoint (8 weeks)

Outcome Measure Data

Analysis Population Description

These correlation analyses were done only on participants in the vortioxetine arm and did not include the group of healthy controls

Arm/Group Title	Vortioxetine
Arm/Group Description	vortioxetine 5-20 mg/day
Measure Participants	25
AOB P200 amplitude Baseline	4.04 (2.60)
AOB P200 amplitude Endpoint (8 weeks)	3.96 (2.31)
AOB P3a amplitude Baseline	9.43 (5.00)
AOB P3a amplitude Endpoint (8 weeks)	7.13 (4.10)
AOB P3b amplitude Baseline	6.48 (3.69)
AOB P3b amplitude Endpoint (8 weeks)	6.75 (4.30)
VGNG P200 amplitude Baseline	3.40 (1.37)
VGNG P200 amplitude Endpoint (8 weeks)	3.66 (1.53)
VGNG P3a amplitude Baseline	3.33 (1.60)
VGNG P3a amplitude Endpoint (8 weeks)	3.55 (1.77)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P200 (amplitude) and HDRS-28 baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.859
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.044
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	AOB P3a (amplitude)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.451
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.211
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	AOB P3b (amplitude)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.957
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.015
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	VGNG P200 (amplitude)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.166
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.322
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	VGNG P3a (amplitude)
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.105
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.374
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P200 (amplitude) and HDRS-28 baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.601
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.137
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3a (amplitude) and HDRS-28 baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.421
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.234
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3b (amplitude) and HDRS-28 baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.316
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.378
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.478
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.185
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3a (amplitude) and HDRS-28 baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.969
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.011
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P200 (amplitude) and HDRS-17 baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.943
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.018
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3a (amplitude) and HDRS-17 baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.795
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.074
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3b (amplitude) and HDRS-17 baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.969
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.011
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P200 (amplitude) and HDRS-17 baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.406
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.197
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P3a (amplitude) and HDRS-17 baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.185
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.309
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P200 (amplitude) and HDRS-17 baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.454
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.195
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3a (amplitude) and HDRS-17 baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.579
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.162
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3b (amplitude) and HDRS-17 baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.549
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.232
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P200 (amplitude) and HDRS-17 baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.518
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.169
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P3a (amplitude) and HDRS-17 baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.922
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.027
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P200 (amplitude) and QIDS-SR baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.796
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.064
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3a (amplitude) and QIDS-SR baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.054
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.506
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3b (amplitude) and QIDS-SR baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.995
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.002
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P200 (amplitude) and QIDS-SR baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.668
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.102
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P3a (amplitude) and QIDS-SR baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.875
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.037
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P200 (amplitude) and QIDS-SR baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.852
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.049
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3a (amplitude) and QIDS-SR baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.234
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.340
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.056
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.655
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P200 (amplitude) and QIDS-SR baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.248
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.297
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P3a (amplitude) and QIDS-SR baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.507
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.179
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P200 (amplitude) and PDQ baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.841
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.049
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3a (amplitude) and PDQ baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.508
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.185
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3b (amplitude) and PDQ baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.916
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.030
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P200 (amplitude) and PDQ baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.147
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.345
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P3a (amplitude) and PDQ baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.225
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.284
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P200 (amplitude) and PDQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.868
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.044
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 37

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3a (amplitude) and PDQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.537
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.180
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 38

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3b (amplitude) and PDQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.195
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.476
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 39

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P200 (amplitude) and PDQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.015
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.594
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 40

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P3a (amplitude) and PDQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.972
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.009
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 41

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P200 (amplitude) and MGH-CPFQ baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.785
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.067
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 42

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3a (amplitude) and MGH-CPFQ baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.646
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.129
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 43

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3b (amplitude) and MGH-CPFQ baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.182
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.364
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 44

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P200 (amplitude) and MGH-CPFQ baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.069
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.414
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 45

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P3a (amplitude) and MGH-CPFQ baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.068
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.416
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 46

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P200 (amplitude) and MGH-CPFQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.929
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.023
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 47

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3a (amplitude) and MGH-CPFQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.802
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.074
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 48

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3b (amplitude) and MGH-CPFQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.153
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.518
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 49

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P200 (amplitude) and MGH-CPFQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.298
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.268
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 50

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P3a (amplitude) and MGH-CPFQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.996
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.001
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 51

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P200 (amplitude) and WLQ baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.531
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.242
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 52

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3a (amplitude) and WLQ baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.210
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.598
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 53

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3b (amplitude) and WLQ baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.899
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.054
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 54

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.087
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.568
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 55

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P3a (amplitude) and WLQ baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.087
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.568
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 56

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P200 (amplitude) and WLQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.550
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.231
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 57

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3a (amplitude) and WLQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.766
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.158
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 58

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3b (amplitude) and WLQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.498
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.406
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 59

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P200 (amplitude) and WLQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.599
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.221
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 60

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P3a (amplitude) and WLQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.064
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.679
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Correlations Between BNA Latency Scores and Clinical, Cognitive, and Functionality Assessments Using Baseline Scores
Description	Pearson correlation was used to examine the associations between baseline BNA latency scores and outcomes including measures of MDD symptoms, cognitive function and functionality.
Time Frame	Baseline to Endpoint (8 weeks)

Outcome Measure Data

Analysis Population Description

These correlation analyses were done only on participants in the vortioxetine arm and did not include the group of healthy controls

Arm/Group Title	Vortioxetine
Arm/Group Description	vortioxetine 5-20 mg/day
Measure Participants	25
AOB P200 latency Baseline	177.37 (12.66)
AOB P200 latency Endpoint (8 weeks)	177.90 (14.12)
AOB P3a latency Baseline	308.47 (50.93)
AOB P3a latency Endpoint (8 weeks)	281.38 (40.63)
AOB P3b latency Baseline	370.07 (55.87)
AOB P3b latency Endpoint (8 weeks)	367.27 (37.59)
VGNG P200 latency Baseline	170.35 (14.05)
VGNG P200 latency Endpoint (8 weeks)	172.11 (16.35)
VGNG P3a latency Baseline	433.75 (24.91)
VGNG P3a latency Endpoint (8 weeks)	431.44 (32.36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P200 (latency) and HDRS-28 baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.881
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.038
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3a (latency) and HDRS-28 baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.279
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.299
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3b (latency) and HDRS-28 baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.039
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.538
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P200 (latency) and HDRS-28 baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.940
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.018
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P3a (latency) and HDRS-28 baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.65
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.107
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P200 (latency) and HDRS-28 baseline to endpoint percentage change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.340
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.247
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3a (latency) and HDRS-28 baseline to endpoint percentage change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.819
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.067
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3b (latency) and HDRS-28 baseline to endpoint percentage change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.400
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.321
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P200 (latency) and HDRS-28 baseline to endpoint percentage change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.278
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.279
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P3a (latency) and HDRS-28 baseline to endpoint percentage change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.614
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.136
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P200 (latency) and HDRS-17 baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.999
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.000
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3a (latency) and HDRS-17 baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.491
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.193
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3b (latency) and HDRS-17 baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.028
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.567
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P200 (latency) and HDRS-17 baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.900
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.030
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P3a (latency) and HDRS-17 baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.55
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.141
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P200 (latency) and HDRS-17 baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.373
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.231
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 17

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3a (latency) and HDRS-17 baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.949
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.019
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 18

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3b (latency) and HDRS-17 baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.754
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.122
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 19

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P200 (latency) and HDRS-17 baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.499
	Comments
	Method	0.176
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.176
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 20

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P3a (latency) and HDRS-17 baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.549
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.162
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 21

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P200 (latency) and QIDS-SR baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.617
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.126
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 22

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3a (latency) and QIDS-SR baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.722
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.100
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 23

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3b (latency) and QIDS-SR baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.371
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.249
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 24

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P200 (latency) and QIDS-SR baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.764
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.072
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 25

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P3a (latency) and QIDS-SR baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.34
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.225
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 26

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P200 (latency) and QIDS-SR baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.570
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.148
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 27

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3a (latency) and QIDS-SR baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.434
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.228
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 28

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3b (latency) and QIDS-SR baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.569
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.220
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 29

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P200 (latency) and QIDS-SR baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.005
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.645
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 30

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P3a (latency) and QIDS-SR baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.698
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.105
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 31

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P200 (latency) and PDQ baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.774
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.073
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 32

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3a (latency) and PDQ baseline score
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.024
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.577
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 33

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3b (latency) and PDQ baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.603
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.146
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 34

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P200 (latency) and PDQ baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.326
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.232
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 35

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P3a (latency) and PDQ baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.68
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.098
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 36

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P200 (latency) and PDQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.774
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.073
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 37

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3a (latency) and PDQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.024
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.577
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 38

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3b (latency) and PDQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.603
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.146
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 39

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P200 (latency) and PDQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.326
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.232
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 40

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P3a (latency) and PDQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.68
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.098
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 41

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P200 (latency) and MGH-CPFQ baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.692
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.100
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 42

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3a (latency) and MGH-CPFQ baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.059
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.498
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 43

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3b (latency) and MGH-CPFQ baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.227
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.332
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 44

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P200 (latency) and MGH-CPFQ baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.600
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.125
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 45

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P3a (latency) and MGH-CPFQ baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.69
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.096
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 46

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P200 (latency) and MGH-CPFQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.315
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.259
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 47

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3a (latency) and MGH-CPFQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.996
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.002
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 48

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3b (latency) and MGH-CPFQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.544
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.234
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 49

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P200 (latency) and MGH-CPFQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.066
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.455
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 50

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P3a (latency) and MGH-CPFQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.293
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.280
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 51

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P200 (latency) and WLQ baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.013
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.783
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 52

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3a (latency) and WLQ baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.799
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.135
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 53

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3b (latency) and WLQ baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.201
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.506
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 54

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P200 (latency) and WLQ baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.586
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.197
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 55

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P3a (latency) and WLQ baseline scores
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.95
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.024
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 56

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P200 (latency) and WLQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.920
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.039
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 57

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3a (latency) and WLQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.831
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.113
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 58

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between AOB P3b (latency) and WLQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.230
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	0.655
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 59

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P200 (latency) and WLQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.115
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.602
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 60

Statistical Analysis Overview	Comparison Group Selection	Vortioxetine
	Comments	Correlation between VGNG P3a (latency) and WLQ baseline to endpoint percent change
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.450
	Comments
	Method	Pearson's correlation
	Comments
Method of Estimation	Estimation Parameter	Pearson's R
	Estimated Value	-0.313
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	8 weeks
Arm/Group Title	Vortioxetine
Arm/Group Description	vortioxetine 5-20 mg/day
All Cause Mortality
	Vortioxetine
	Affected / at Risk (%)	# Events
Total	0/25 (0%)
Serious Adverse Events
	Vortioxetine
	Affected / at Risk (%)	# Events
Total	0/25 (0%)
Other (Not Including Serious) Adverse Events
	Vortioxetine
	Affected / at Risk (%)	# Events
Total	9/25 (36%)
Gastrointestinal disorders
Nausea	9/25 (36%)
Diarrhea	4/25 (16%)
General disorders
Headache	7/25 (28%)
Upper respiratory infection	6/25 (24%)
Insomnia	4/25 (16%)
Somnolence	3/25 (12%)
Esophageal reflux	2/25 (8%)
Sweating	2/25 (8%)
Dental/tooth pain	2/25 (8%)

Limitations/Caveats

Secondary outcomes #4 and #7, part c were not included in the results section for the following reasons: analysis became too complex based on low sample size; too many subgroups were needed. There were changes in BNA regardless of changes in symptoms and couldn't isolate meaningful or clinical useful data. In addition, several cognitive and functionality scores (i.e., CGI-I, TMT, UPSA, Stroop) were not collected at baseline and therefore not included in the "correlation with BNA" analysis.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.