Trial Outcomes & Findings for Mechanisms of Antidepressant Non-Response in Late-Life Depression (NCT NCT01931202)

NCT ID: NCT01931202

Last Updated: 2020-07-02

Results Overview

Our target is depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD). The HRSD is a 24-item questionnaire used as an indication of depression and a guide to evaluate recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score of 16 or above is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 138 participants
• Primary outcome timeframe: Baseline
• Results posted on: 2020-07-02

Participant Flow

138 subjects signed consent, 108 were randomized to one of the 3 arms therefore they cannot be classified to any of the below arms.

Participant milestones

Measure	Double Blind-Placebo Group Blinded treatment with placebo, one pill a day. If after the 4 weeks, the patient has not remitted, they will be increased to 2 pills a day.	Double Blind-Escitalopram Group Blinded treatment with escitalopram 10mg increased to escitalopram 20mg or placebo at week 4 if depression has not remitted Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.	Open Treatment With Escitalopram Open treatment with 10mg of escitalopram, increased to 20mg if depression has not remitted at week 4. Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.
Overall Study STARTED	8	51	49
Overall Study COMPLETED	8	46	45
Overall Study NOT COMPLETED	0	5	4

Reasons for withdrawal

Measure	Double Blind-Placebo Group Blinded treatment with placebo, one pill a day. If after the 4 weeks, the patient has not remitted, they will be increased to 2 pills a day.	Double Blind-Escitalopram Group Blinded treatment with escitalopram 10mg increased to escitalopram 20mg or placebo at week 4 if depression has not remitted Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.	Open Treatment With Escitalopram Open treatment with 10mg of escitalopram, increased to 20mg if depression has not remitted at week 4. Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.
Overall Study Withdrawal by Subject	0	0	2
Overall Study Lost to Follow-up	0	5	2

Baseline Characteristics

Mechanisms of Antidepressant Non-Response in Late-Life Depression

Baseline characteristics by cohort

Measure	Placebo n=8 Participants Blinded treatment with placebo. Placebo oral tablet: Inert substance or treatment which is designed to have no therapeutic value but resemble the active medication in this study	Escitalopram n=51 Participants Blinded treatment with either escitalopram, increased to escitalopram 20mg or placebo at week 4 if depression has not remitted Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.	Open Treatment With Escitalopram n=49 Participants Open treatment with 10mg of escitalopram, increased to 20mg if depression has not remitted at week 4. Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.	Total n=108 Participants Total of all reporting groups
Age, Customized Age at Screening	73.9 years STANDARD_DEVIATION 7.2 • n=5 Participants	70.7 years STANDARD_DEVIATION 8.4 • n=7 Participants	69.2 years STANDARD_DEVIATION 7.2 • n=5 Participants	70.2 years STANDARD_DEVIATION 7.8 • n=4 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	32 Participants n=7 Participants	32 Participants n=5 Participants	70 Participants n=4 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	19 Participants n=7 Participants	17 Participants n=5 Participants	38 Participants n=4 Participants
Race/Ethnicity, Customized Asian	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants
Race/Ethnicity, Customized Black/African American	1 participants n=5 Participants	6 participants n=7 Participants	8 participants n=5 Participants	15 participants n=4 Participants
Race/Ethnicity, Customized White	5 participants n=5 Participants	35 participants n=7 Participants	34 participants n=5 Participants	74 participants n=4 Participants
Race/Ethnicity, Customized More than one	1 participants n=5 Participants	6 participants n=7 Participants	3 participants n=5 Participants	10 participants n=4 Participants
Race/Ethnicity, Customized Don't Know	1 participants n=5 Participants	3 participants n=7 Participants	3 participants n=5 Participants	7 participants n=4 Participants
Race/Ethnicity, Customized Missing	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants
Region of Enrollment United States	8 Participants n=5 Participants	51 Participants n=7 Participants	49 Participants n=5 Participants	108 Participants n=4 Participants
Hamilton Rating Scale for Depression (HRSD)	22.8 units on a scale STANDARD_DEVIATION 4.9 • n=5 Participants	23.6 units on a scale STANDARD_DEVIATION 6.1 • n=7 Participants	22.9 units on a scale STANDARD_DEVIATION 6.3 • n=5 Participants	23.2 units on a scale STANDARD_DEVIATION 6.1 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline

Our target is depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD). The HRSD is a 24-item questionnaire used as an indication of depression and a guide to evaluate recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score of 16 or above is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity.

Outcome measures

Measure	Double Blind-Placebo Group n=8 Participants Blinded treatment with placebo, one pill a day. If after the 4 weeks, the patient has not remitted, they will be increased to 2 pills a day.	Double Blind-Escitalopram Group n=51 Participants Blinded treatment with escitalopram 10mg, increased to escitalopram 20mg at week 4 if depression has not remitted Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.	Open Treatment With Escitalopram n=49 Participants Open treatment with 10mg of escitalopram, increased to 20mg if depression has not remitted at week 4. Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.
Hamilton Rating Scale for Depression (HRSD)	22.8 units on a scale Standard Deviation 4.9	23.6 units on a scale Standard Deviation 6.1	22.9 units on a scale Standard Deviation 6.3

SECONDARY outcome

Timeframe: Week 8

Population: Although 138 subjects were enrolled (signed consent) and 108 were randomized, only 99 completed the Hamilton Rating Scale for Depression (HRSD) at week 8.

Our target is depressive symptomatology as measured by the Hamilton Rating Scale for Depression (HRSD). The HRSD is a 24-item questionnaire used as an indication of depression and a guide to evaluate recovery. Total scores range from 0-74, not including atypical symptoms sub-scale. A score of 16 or above is typically considered to indicate the presence of depressive symptoms. Higher scores indicate greater severity.

Outcome measures

Measure	Double Blind-Placebo Group n=8 Participants Blinded treatment with placebo, one pill a day. If after the 4 weeks, the patient has not remitted, they will be increased to 2 pills a day.	Double Blind-Escitalopram Group n=46 Participants Blinded treatment with escitalopram 10mg, increased to escitalopram 20mg at week 4 if depression has not remitted Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.	Open Treatment With Escitalopram n=45 Participants Open treatment with 10mg of escitalopram, increased to 20mg if depression has not remitted at week 4. Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.
Hamilton Rating Scale for Depression (HRSD)	13.25 units on a scale Standard Deviation 5.50	14.39 units on a scale Standard Deviation 8.13	11.67 units on a scale Standard Deviation 7.58

SECONDARY outcome

Timeframe: Baseline

Population: 138 subjects were consented, of which 108 were randomized, however only 107 completed baseline Quick Inventory of Depressive Symptoms (QIDS-SR).

QIDS-SR is a 16 item scale self-report form that was used to measure depression outcomes. This self-report is valuable in this study, because it is less susceptible to clinician and rater bias. The QIDS-SR has been increasingly used in antidepressant studies due to its equivalent weightings for each symptom item, clearly understandable anchor points, and inclusion of all DSM criteria for depression. The scores range from 0-27 with 27 being worse depressive symptoms.

Outcome measures

Measure	Double Blind-Placebo Group n=8 Participants Blinded treatment with placebo, one pill a day. If after the 4 weeks, the patient has not remitted, they will be increased to 2 pills a day.	Double Blind-Escitalopram Group n=50 Participants Blinded treatment with escitalopram 10mg, increased to escitalopram 20mg at week 4 if depression has not remitted Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.	Open Treatment With Escitalopram n=49 Participants Open treatment with 10mg of escitalopram, increased to 20mg if depression has not remitted at week 4. Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.
Quick Inventory of Depressive Symptoms (QIDS-SR)	12.4 units on a scale Standard Deviation 4.4	13.5 units on a scale Standard Deviation 4.5	13.0 units on a scale Standard Deviation 4.7

SECONDARY outcome

Timeframe: Week 8

Population: 138 subjects were consented, of which 108 were randomized, however only 99 completed week 8 Quick Inventory of Depressive Symptoms (QIDS-SR).

QIDS-SR is a 16 item scale self-report form that was used to measure depression outcomes. This self-report is valuable in this study, because it is less susceptible to clinician and rater bias. The QIDS-SR has been increasingly used in antidepressant studies due to its equivalent weightings for each symptom item, clearly understandable anchor points, and inclusion of all DSM criteria for depression. The scores range from 0-27 with 27 being worse depressive symptoms.

Outcome measures

Measure	Double Blind-Placebo Group n=8 Participants Blinded treatment with placebo, one pill a day. If after the 4 weeks, the patient has not remitted, they will be increased to 2 pills a day.	Double Blind-Escitalopram Group n=46 Participants Blinded treatment with escitalopram 10mg, increased to escitalopram 20mg at week 4 if depression has not remitted Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.	Open Treatment With Escitalopram n=44 Participants Open treatment with 10mg of escitalopram, increased to 20mg if depression has not remitted at week 4. Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.
Quick Inventory of Depressive Symptoms (QIDS-SR)	8.00 units on a scale Standard Deviation 2.93	6.93 units on a scale Standard Deviation 5.14	6.34 units on a scale Standard Deviation 5.31

SECONDARY outcome

Timeframe: Pre-Baseline

Population: 138 subjects were consented, of which 108 were randomized, however only 101 completed pre-baseline Credibility and Expectancy Scale-Better (CES).

CES is an 8 item scale in which subjects rate their impression of the credibility of the treatment and how they estimate their expectation of improvement. The CES is the most widely used measure of expectancy and has demonstrated good psychometric properties in multiple studies. Question 2 ('Better') asks the patient the chances of their depression being completely better at the end of this study, from 1 = very poor to 7 = very good. The higher the number, the higher the expectancy that they will be better.

Outcome measures

Measure	Double Blind-Placebo Group n=8 Participants Blinded treatment with placebo, one pill a day. If after the 4 weeks, the patient has not remitted, they will be increased to 2 pills a day.	Double Blind-Escitalopram Group n=46 Participants Blinded treatment with escitalopram 10mg, increased to escitalopram 20mg at week 4 if depression has not remitted Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.	Open Treatment With Escitalopram n=47 Participants Open treatment with 10mg of escitalopram, increased to 20mg if depression has not remitted at week 4. Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.
Credibility and Expectancy Scale-Better (CES)	6 units on a scale Standard Deviation 1.1	5.5 units on a scale Standard Deviation 1.2	5.3 units on a scale Standard Deviation 1.3

SECONDARY outcome

Timeframe: Week 0

Population: 138 subjects were consented, of which 108 were randomized, however only 106 completed week 0 Credibility and Expectancy Scale-Better (CES).

CES is an 8 item scale in which subjects rate their impression of the credibility of the treatment and how they estimate their expectation of improvement. The CES is the most widely used measure of expectancy and has demonstrated good psychometric properties in multiple studies. Question 2 ('Better') asks the patient the chances of their depression being completely better at the end of this study, from 1 = very poor to 7 = very good. The higher the number, the higher the expectancy that they will be better.

Outcome measures

Measure	Double Blind-Placebo Group n=8 Participants Blinded treatment with placebo, one pill a day. If after the 4 weeks, the patient has not remitted, they will be increased to 2 pills a day.	Double Blind-Escitalopram Group n=50 Participants Blinded treatment with escitalopram 10mg, increased to escitalopram 20mg at week 4 if depression has not remitted Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.	Open Treatment With Escitalopram n=48 Participants Open treatment with 10mg of escitalopram, increased to 20mg if depression has not remitted at week 4. Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.
Credibility and Expectancy Scale-Better (CES)	5.63 units on a scale Standard Deviation 0.92	5.00 units on a scale Standard Deviation 1.36	5.67 units on a scale Standard Deviation 1.40

SECONDARY outcome

Timeframe: Pre-baseline

Population: 138 subjects were consented, of which 108 were randomized, however only 101 completed pre-baseline Credibility and Expectancy Scale-Depression.

CES is an 8 item scale in which subjects rate their impression of the credibility of the treatment and how they estimate their expectation of improvement. The CES is the most widely used measure of expectancy and has demonstrated good psychometric properties in multiple studies. CES question 3 ('Depression') asks how the patient's depression will be at the end of the study, compared with now, from 1 = much worse to 7= much better. The higher the number, the higher the expectancy that their depression will be much better.

Outcome measures

Measure	Double Blind-Placebo Group n=8 Participants Blinded treatment with placebo, one pill a day. If after the 4 weeks, the patient has not remitted, they will be increased to 2 pills a day.	Double Blind-Escitalopram Group n=46 Participants Blinded treatment with escitalopram 10mg, increased to escitalopram 20mg at week 4 if depression has not remitted Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.	Open Treatment With Escitalopram n=47 Participants Open treatment with 10mg of escitalopram, increased to 20mg if depression has not remitted at week 4. Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.
Credibility and Expectancy Scale-Depression	6.3 units on a scale Standard Deviation 1.2	6.0 units on a scale Standard Deviation 0.9	5.9 units on a scale Standard Deviation 0.9

SECONDARY outcome

Timeframe: Week 0

Population: 138 subjects were consented, of which 108 were randomized, however only 106 completed week 0 Credibility and Expectancy Scale-Depression.

CES is an 8 item scale in which subjects rate their impression of the credibility of the treatment and how they estimate their expectation of improvement. The CES is the most widely used measure of expectancy and has demonstrated good psychometric properties in multiple studies. CES question 3 ('Depression') asks how the patient's depression will be at the end of the study, compared with now, from 1 = much worse to 7= much better. The higher the number, the higher the expectancy that their depression will be much better.

Outcome measures

Measure	Double Blind-Placebo Group n=8 Participants Blinded treatment with placebo, one pill a day. If after the 4 weeks, the patient has not remitted, they will be increased to 2 pills a day.	Double Blind-Escitalopram Group n=50 Participants Blinded treatment with escitalopram 10mg, increased to escitalopram 20mg at week 4 if depression has not remitted Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.	Open Treatment With Escitalopram n=48 Participants Open treatment with 10mg of escitalopram, increased to 20mg if depression has not remitted at week 4. Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.
Credibility and Expectancy Scale-Depression	5.88 units on a scale Standard Deviation 0.99	5.40 units on a scale Standard Deviation 1.09	6.06 units on a scale Standard Deviation 0.84

SECONDARY outcome

Timeframe: Pre-Baseline

Population: 138 subjects were consented, of which 108 were randomized, however only 101 completed pre-baseline Quick Inventory of Depression Scale (QIDS-SR): Expectancy.

This 16-items assessment is used to rate the 9 criterion symptom domains of a major depressive episode: 4 items are used to rate sleep disturbance (early, middle, and late insomnia plus hypersomnia); 2 items are used to rate psychomotor disturbance (agitation and retardation); 4 items are used to rate appetite/weight disturbance (appetite increase or decrease and weight increase or decrease). Only 1 item is used to rate the remaining 6 domains (depressed mood, decreased interest, decreased energy, worthlessness/guilt, concentration/decision making, and suicidal ideation). Each item is rated 0-3. For symptom domains that require more than 1 item, the highest score of the item relevant for each domain is taken. The total score ranges from 0-27. A lower rating indicates higher expectancy of improvement and lower expectation of depressive symptomatology, and a higher rating indicates lower expectancy of improvement, higher expectation of depression.

Outcome measures

Measure	Double Blind-Placebo Group n=8 Participants Blinded treatment with placebo, one pill a day. If after the 4 weeks, the patient has not remitted, they will be increased to 2 pills a day.	Double Blind-Escitalopram Group n=46 Participants Blinded treatment with escitalopram 10mg, increased to escitalopram 20mg at week 4 if depression has not remitted Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.	Open Treatment With Escitalopram n=47 Participants Open treatment with 10mg of escitalopram, increased to 20mg if depression has not remitted at week 4. Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.
Quick Inventory of Depression Scale (QIDS-SR): Expectancy	5.3 units on a scale Standard Deviation 6.2	4.8 units on a scale Standard Deviation 3.7	5.8 units on a scale Standard Deviation 4.5

SECONDARY outcome

Timeframe: Week 0

Population: 138 subjects were consented, of which 108 were randomized, however only 107 completed week 0 Quick Inventory of Depression Scale (QIDS-SR): Expectancy.

This 16-items assessment is used to rate the 9 criterion symptom domains of a major depressive episode: 4 items are used to rate sleep disturbance (early, middle, and late insomnia plus hypersomnia); 2 items are used to rate psychomotor disturbance (agitation and retardation); 4 items are used to rate appetite/weight disturbance (appetite increase or decrease and weight increase or decrease). Only 1 item is used to rate the remaining 6 domains (depressed mood, decreased interest, decreased energy, worthlessness/guilt, concentration/decision making, and suicidal ideation). Each item is rated 0-3. For symptom domains that require more than 1 item, the highest score of the item relevant for each domain is taken. The total score ranges from 0-27. A lower rating indicates higher expectancy of improvement and lower expectation of depressive symptomatology, and a higher rating indicates lower expectancy of improvement, higher expectation of depression.

Outcome measures

Measure	Double Blind-Placebo Group n=8 Participants Blinded treatment with placebo, one pill a day. If after the 4 weeks, the patient has not remitted, they will be increased to 2 pills a day.	Double Blind-Escitalopram Group n=50 Participants Blinded treatment with escitalopram 10mg, increased to escitalopram 20mg at week 4 if depression has not remitted Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.	Open Treatment With Escitalopram n=49 Participants Open treatment with 10mg of escitalopram, increased to 20mg if depression has not remitted at week 4. Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.
Quick Inventory of Depression Scale (QIDS-SR): Expectancy	6.63 units on a scale Standard Deviation 3.42	6.20 units on a scale Standard Deviation 4.83	4.92 units on a scale Standard Deviation 3.83

SECONDARY outcome

Timeframe: Pre-Baseline

Population: 138 subjects were consented, of which 108 were randomized, however only 106 completed pre-baseline Executive Dysfunction: Stroop Color Word.

Stroop Color Word test asks patients to name the color of a word rather than reading the word. Stroop Color Word is how many colors they can name in 45 sec (higher is better, e.g., less executive dysfunction).

Outcome measures

Measure	Double Blind-Placebo Group n=7 Participants Blinded treatment with placebo, one pill a day. If after the 4 weeks, the patient has not remitted, they will be increased to 2 pills a day.	Double Blind-Escitalopram Group n=50 Participants Blinded treatment with escitalopram 10mg, increased to escitalopram 20mg at week 4 if depression has not remitted Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.	Open Treatment With Escitalopram n=49 Participants Open treatment with 10mg of escitalopram, increased to 20mg if depression has not remitted at week 4. Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.
Executive Dysfunction: Stroop Color Word	31.7 correct items Standard Deviation 6.1	31.0 correct items Standard Deviation 9.0	32.6 correct items Standard Deviation 11.0

SECONDARY outcome

Timeframe: Pre-Baseline

Population: 138 subjects were consented, of which 108 were randomized, however only 105 completed pre-baseline Executive Dysfunction: Stroop Interference.

The Stroop is a measure of inhibition under distracting conditions that is sensitive to frontal lobe dysfunction. in Stroop Color Word test patients are to name the color of a word rather than reading the word. Stroop Color Word is how many colors they can name in 45 sec (higher is better, e.g., less executive dysfunction). Stroop Interference is this score adjusted for age and education.

Outcome measures

Measure	Double Blind-Placebo Group n=6 Participants Blinded treatment with placebo, one pill a day. If after the 4 weeks, the patient has not remitted, they will be increased to 2 pills a day.	Double Blind-Escitalopram Group n=50 Participants Blinded treatment with escitalopram 10mg, increased to escitalopram 20mg at week 4 if depression has not remitted Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.	Open Treatment With Escitalopram n=49 Participants Open treatment with 10mg of escitalopram, increased to 20mg if depression has not remitted at week 4. Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.
Executive Dysfunction: Stroop Interference	42.2 correct items Standard Deviation 6.8	42.9 correct items Standard Deviation 11.2	44.1 correct items Standard Deviation 10.4

SECONDARY outcome

Timeframe: Pre-Baseline

Population: 138 subjects signed consent and 108 were randomized, however not all participants underwent MRI scanning.

Magnetic Resonance Imaging (MRI) of the Brain was acquired. We rated the severity of WMH on axial T2 FLAIR images using the Fazekas modified Coffey Rating Scale. Deep WMH are scored as 0 (absent), 1 (punctate foci), 2 (beginning confluence of foci), and 3 (large confluent areas); subcortical gray matter HIs (basal ganglia) are scored as 0 (absent), 1 (punctate), 2 (multipunctate), and 3 (diffuse); periventricular HIs are scored as 0 (absent), 1 (caps), 2 (smooth halo), and 3 (irregular and extending into the deep white matter). Our primary measure of WMH burden will be DWMH score, which has been used to establish the only empirically validated diagnostic criteria for vascular depression, where scores of 0-1 were normal, but 2-3 indicated WHM.

Outcome measures

Measure	Double Blind-Placebo Group n=5 Participants Blinded treatment with placebo, one pill a day. If after the 4 weeks, the patient has not remitted, they will be increased to 2 pills a day.	Double Blind-Escitalopram Group n=28 Participants Blinded treatment with escitalopram 10mg, increased to escitalopram 20mg at week 4 if depression has not remitted Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.	Open Treatment With Escitalopram n=33 Participants Open treatment with 10mg of escitalopram, increased to 20mg if depression has not remitted at week 4. Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.
White Matter Hyperintensity (WMH) Outcome- Total WMH	2.3 score on a scale Standard Deviation 1.7	2.1 score on a scale Standard Deviation 1.9	1.9 score on a scale Standard Deviation 2.2

Adverse Events

Double Blind-Placebo Group

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Double Blind-Escitalopram Group

Serious events: 2 serious events

Other events: 0 other events

Deaths: 0 deaths

Open Treatment With Escitalopram

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Double Blind-Placebo Group n=8 participants at risk Blinded treatment with placebo, 1 pill a day for 4 weeks. At week 4, if patients have not remitted, they were increased to 2 pills a day.	Double Blind-Escitalopram Group n=51 participants at risk Blinded treatment with either escitalopram 10mg, increased to escitalopram 20mg at week 4 if depression has not remitted Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.	Open Treatment With Escitalopram n=49 participants at risk Open treatment with 10mg of escitalopram, increased to 20mg if depression has not remitted at week 4. Escitalopram: Escitalopram is an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class. It is FDA approved for the treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD) in adults and children over 12 years of age.
Nervous system disorders Fall	0.00% 0/8 • Adverse events were collected through the 8 week period of the study. Adverse events were collected during weekly visit with the patients.	3.9% 2/51 • Number of events 2 • Adverse events were collected through the 8 week period of the study. Adverse events were collected during weekly visit with the patients.	0.00% 0/49 • Adverse events were collected through the 8 week period of the study. Adverse events were collected during weekly visit with the patients.
Respiratory, thoracic and mediastinal disorders Chest Pain	0.00% 0/8 • Adverse events were collected through the 8 week period of the study. Adverse events were collected during weekly visit with the patients.	0.00% 0/51 • Adverse events were collected through the 8 week period of the study. Adverse events were collected during weekly visit with the patients.	2.0% 1/49 • Number of events 1 • Adverse events were collected through the 8 week period of the study. Adverse events were collected during weekly visit with the patients.

Other adverse events

Adverse event data not reported

Additional Information

Bret R. Rutherford

New York State Psychiatric Institute

Phone: 6467748660

Email: bret.rutherford@nyspi.columbia.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place