Trial Outcomes & Findings for Neural Mechanisms of Monoaminergic Engagement in Late-life Depression Treatment Response (NEMO) (NCT NCT03128021)
NCT ID: NCT03128021
Last Updated: 2025-03-10
Results Overview
Treatment response will be defined as either a MADRS score of less than 12 or 30% or greater reduction in MADRS score.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
57 participants
Primary outcome timeframe
Change in Baseline MADRS score through Week 12
Results posted on
2025-03-10
Participant Flow
Participant milestones
| Measure |
Escitalopram Pill
Participants in this arm will receive an initial dose of 5 mg. Further titrations will be decided based on clinical response and tolerability (maximum dose of 20 mg). The medication will be taken by mouth in pill form, once daily.
Escitalopram Pill: Double-blinded, randomly assigned
|
Placebo
Participants will be given a sugar pill (placebo) to be taken by mouth once daily for the 6 week duration of Phase I. As this arm is also double-blinded, participants will receive an initial dose of 5 mg and further titrations (maximum dose of 20 mg) will be decided based on clinical response and tolerability.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima.
Placebo: Double-blinded, randomly assigned
|
Escitalopram Pill (Phase II)
Participants who were in the placebo arm for Phase I who do not show signs of response to treatment by week 6 (defined as either a MADRS score of greater than 12 or less than a 30% reduction in MADRS score to be deemed a non-responder) will be given the option to have an open-label trial of escitalopram in Phase II.
Participants in this arm will receive an initial dose of 5 mg. Further titrations throughout the 6 week duration of Phase 2 (maximum dose of 20 mg) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima and the assignment does not change throughout the study.
Escitalopram Pill: Double-blinded, randomly assigned
|
Levomilnacipran Pill
Participants will receive an initial dose of 20 mg blinded levomilnacipran. At day 7, the doses will be titrated to 40 mg of levomilnacipran. Further titrations (maximum dose of 120 mg of levomilnacipran) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Levomilnacipran Pill: Double-blinded, randomly assigned
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
25
|
4
|
6
|
22
|
|
Overall Study
COMPLETED
|
20
|
2
|
4
|
9
|
|
Overall Study
NOT COMPLETED
|
5
|
2
|
2
|
13
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
8 participants were eligible after screening measures, were randomized, but were then terminated from the study before "baseline" MADRS scores were recorded.
Baseline characteristics by cohort
| Measure |
Escitalopram Pill
n=25 Participants
Participants in this arm will receive an initial dose of 5 mg. Further titrations will be decided based on clinical response and tolerability (maximum dose of 20 mg). The medication will be taken by mouth in pill form, once daily.
Escitalopram Pill: Double-blinded, randomly assigned
|
Placebo
n=4 Participants
Participants will be given a sugar pill (placebo) to be taken by mouth once daily for the 6 week duration of Phase I. As this arm is also double-blinded, participants will receive an initial dose of 5 mg and further titrations (maximum dose of 20 mg) will be decided based on clinical response and tolerability.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima.
Placebo: Double-blinded, randomly assigned
|
Escitalopram Pill (Phase II)
n=6 Participants
Participants who were in the placebo arm for Phase I who do not show signs of response to treatment by week 6 (defined as either a MADRS score of greater than 12 or less than a 30% reduction in MADRS score to be deemed a non-responder) will be given the option to have an open-label trial of escitalopram in Phase II.
Participants in this arm will receive an initial dose of 5 mg. Further titrations throughout the 6 week duration of Phase 2 (maximum dose of 20 mg) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima and the assignment does not change throughout the study.
Escitalopram Pill: Double-blinded, randomly assigned
|
Levomilnacipran Pill
n=22 Participants
Participants will receive an initial dose of 20 mg blinded levomilnacipran. At day 7, the doses will be titrated to 40 mg of levomilnacipran. Further titrations (maximum dose of 120 mg of levomilnacipran) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Levomilnacipran Pill: Double-blinded, randomly assigned
|
Total
n=57 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
68.13 age at randomzation
STANDARD_DEVIATION 6.29 • n=25 Participants
|
63.74 age at randomzation
STANDARD_DEVIATION 3.02 • n=4 Participants
|
64.47 age at randomzation
STANDARD_DEVIATION 2.17 • n=6 Participants
|
68.43 age at randomzation
STANDARD_DEVIATION 7.72 • n=22 Participants
|
67.55 age at randomzation
STANDARD_DEVIATION 6.53 • n=57 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=25 Participants
|
3 Participants
n=4 Participants
|
5 Participants
n=6 Participants
|
10 Participants
n=22 Participants
|
31 Participants
n=57 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=25 Participants
|
1 Participants
n=4 Participants
|
1 Participants
n=6 Participants
|
12 Participants
n=22 Participants
|
26 Participants
n=57 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=25 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=22 Participants
|
1 Participants
n=57 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
24 Participants
n=25 Participants
|
4 Participants
n=4 Participants
|
6 Participants
n=6 Participants
|
22 Participants
n=22 Participants
|
56 Participants
n=57 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=25 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=22 Participants
|
0 Participants
n=57 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=25 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=22 Participants
|
0 Participants
n=57 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=25 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=22 Participants
|
0 Participants
n=57 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=25 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=22 Participants
|
0 Participants
n=57 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=25 Participants
|
2 Participants
n=4 Participants
|
3 Participants
n=6 Participants
|
3 Participants
n=22 Participants
|
11 Participants
n=57 Participants
|
|
Race (NIH/OMB)
White
|
22 Participants
n=25 Participants
|
2 Participants
n=4 Participants
|
3 Participants
n=6 Participants
|
18 Participants
n=22 Participants
|
45 Participants
n=57 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=25 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=6 Participants
|
1 Participants
n=22 Participants
|
1 Participants
n=57 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=25 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=6 Participants
|
0 Participants
n=22 Participants
|
0 Participants
n=57 Participants
|
|
Region of Enrollment
United States
|
25 participants
n=25 Participants
|
4 participants
n=4 Participants
|
6 participants
n=6 Participants
|
22 participants
n=22 Participants
|
57 participants
n=57 Participants
|
|
Montgomery Asberg Depression Rating Scale
|
19.43 units on a scale
STANDARD_DEVIATION 6.68 • n=23 Participants • 8 participants were eligible after screening measures, were randomized, but were then terminated from the study before "baseline" MADRS scores were recorded.
|
25.33 units on a scale
STANDARD_DEVIATION 5.51 • n=3 Participants • 8 participants were eligible after screening measures, were randomized, but were then terminated from the study before "baseline" MADRS scores were recorded.
|
23.83 units on a scale
STANDARD_DEVIATION 5.19 • n=6 Participants • 8 participants were eligible after screening measures, were randomized, but were then terminated from the study before "baseline" MADRS scores were recorded.
|
21.94 units on a scale
STANDARD_DEVIATION 6.35 • n=17 Participants • 8 participants were eligible after screening measures, were randomized, but were then terminated from the study before "baseline" MADRS scores were recorded.
|
21.20 units on a scale
STANDARD_DEVIATION 6.45 • n=49 Participants • 8 participants were eligible after screening measures, were randomized, but were then terminated from the study before "baseline" MADRS scores were recorded.
|
PRIMARY outcome
Timeframe: Change in Baseline MADRS score through Week 12Treatment response will be defined as either a MADRS score of less than 12 or 30% or greater reduction in MADRS score.
Outcome measures
| Measure |
Escitalopram Pill
n=20 Participants
Participants in this arm will receive an initial dose of 5 mg. Further titrations will be decided based on clinical response and tolerability (maximum dose of 20 mg). The medication will be taken by mouth in pill form, once daily.
Escitalopram Pill: Double-blinded, randomly assigned
|
Placebo
n=2 Participants
Participants will be given a sugar pill (placebo) to be taken by mouth once daily for the 6 week duration of Phase I. As this arm is also double-blinded, participants will receive an initial dose of 5 mg and further titrations (maximum dose of 20 mg) will be decided based on clinical response and tolerability.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima.
Placebo: Double-blinded, randomly assigned
|
Escitalopram Pill (Phase II)
n=4 Participants
Participants who were in the placebo arm for Phase I who do not show signs of response to treatment by week 6 (defined as either a MADRS score of greater than 12 or less than a 30% reduction in MADRS score to be deemed a non-responder) will be given the option to have an open-label trial of escitalopram in Phase II.
Participants in this arm will receive an initial dose of 5 mg. Further titrations throughout the 6 week duration of Phase 2 (maximum dose of 20 mg) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima and the assignment does not change throughout the study.
Escitalopram Pill: Double-blinded, randomly assigned
|
Levomilnacipran Pill
n=9 Participants
Participants will receive an initial dose of 20 mg blinded levomilnacipran. At day 7, the doses will be titrated to 40 mg of levomilnacipran. Further titrations (maximum dose of 120 mg of levomilnacipran) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Levomilnacipran Pill: Double-blinded, randomly assigned
|
Escitalopram Pill (NR)
Participants in this arm will receive an initial dose of 5 mg. Further titrations will be decided based on clinical response and tolerability (maximum dose of 20 mg). The medication will be taken by mouth in pill form, once daily.
Escitalopram Pill: Double-blinded, randomly assigned
|
Placebo (NR)
Participants will be given a sugar pill (placebo) to be taken by mouth once daily for the 6 week duration of Phase I. As this arm is also double-blinded, participants will receive an initial dose of 5 mg and further titrations (maximum dose of 20 mg) will be decided based on clinical response and tolerability.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima.
|
Escitalopram Pill (NR) (Phase II)
Participants who were in the placebo arm for Phase I who do not show signs of response to treatment by week 6 (defined as either a MADRS score of greater than 12 or less than a 30% reduction in MADRS score to be deemed a non-responder) will be given the option to have an open-label trial of escitalopram in Phase II.
Participants in this arm will receive an initial dose of 5 mg. Further titrations throughout the 6 week duration of Phase 2 (maximum dose of 20 mg) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima and the assignment does not change throughout the study.
Escitalopram Pill: Double-blinded, randomly assigned
|
Levomilnacipran Pill (NR)
Participants will receive an initial dose of 20 mg blinded levomilnacipran. At day 7, the doses will be titrated to 40 mg of levomilnacipran. Further titrations (maximum dose of 120 mg of levomilnacipran) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Levomilnacipran Pill: Double-blinded, randomly assigned
|
|---|---|---|---|---|---|---|---|---|
|
Change in Montgomery Asberg Depression Rating Scale Score
|
18 persons with positive treatment response
|
2 persons with positive treatment response
|
3 persons with positive treatment response
|
8 persons with positive treatment response
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: Change in Functional Connectivity from Baseline to Day 1Population: Total participants with available Baseline and Day 1 scans that could be analyzed.
The primary analysis will consist of linear mixed effects models with functional connectivity (for each region of interest) as the outcome measure and group (R \[responder\]/NR\[non-responder\], as defined by MADRS), time and their interaction. The results listed are the difference in Baseline to 12 hours after first dose of medication. The values derived by first preprocessing the raw data using SPM and using the AAL3 atlas to parcellate the images into anatomical brain regions. Then the mean residual time series for each region was calculated and the Pearson correlation between the time series of each region was calculated. Then the mean Pearson correlations between every other region with the region identified were calculated and these correlation values were then standardized to have a mean of 0 and a standard deviation of 1. Higher values indicate stronger and better connectivity.
Outcome measures
| Measure |
Escitalopram Pill
n=15 Participants
Participants in this arm will receive an initial dose of 5 mg. Further titrations will be decided based on clinical response and tolerability (maximum dose of 20 mg). The medication will be taken by mouth in pill form, once daily.
Escitalopram Pill: Double-blinded, randomly assigned
|
Placebo
Participants will be given a sugar pill (placebo) to be taken by mouth once daily for the 6 week duration of Phase I. As this arm is also double-blinded, participants will receive an initial dose of 5 mg and further titrations (maximum dose of 20 mg) will be decided based on clinical response and tolerability.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima.
Placebo: Double-blinded, randomly assigned
|
Escitalopram Pill (Phase II)
n=5 Participants
Participants who were in the placebo arm for Phase I who do not show signs of response to treatment by week 6 (defined as either a MADRS score of greater than 12 or less than a 30% reduction in MADRS score to be deemed a non-responder) will be given the option to have an open-label trial of escitalopram in Phase II.
Participants in this arm will receive an initial dose of 5 mg. Further titrations throughout the 6 week duration of Phase 2 (maximum dose of 20 mg) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima and the assignment does not change throughout the study.
Escitalopram Pill: Double-blinded, randomly assigned
|
Levomilnacipran Pill
n=7 Participants
Participants will receive an initial dose of 20 mg blinded levomilnacipran. At day 7, the doses will be titrated to 40 mg of levomilnacipran. Further titrations (maximum dose of 120 mg of levomilnacipran) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Levomilnacipran Pill: Double-blinded, randomly assigned
|
Escitalopram Pill (NR)
n=2 Participants
Participants in this arm will receive an initial dose of 5 mg. Further titrations will be decided based on clinical response and tolerability (maximum dose of 20 mg). The medication will be taken by mouth in pill form, once daily.
Escitalopram Pill: Double-blinded, randomly assigned
|
Placebo (NR)
Participants will be given a sugar pill (placebo) to be taken by mouth once daily for the 6 week duration of Phase I. As this arm is also double-blinded, participants will receive an initial dose of 5 mg and further titrations (maximum dose of 20 mg) will be decided based on clinical response and tolerability.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima.
|
Escitalopram Pill (NR) (Phase II)
n=1 Participants
Participants who were in the placebo arm for Phase I who do not show signs of response to treatment by week 6 (defined as either a MADRS score of greater than 12 or less than a 30% reduction in MADRS score to be deemed a non-responder) will be given the option to have an open-label trial of escitalopram in Phase II.
Participants in this arm will receive an initial dose of 5 mg. Further titrations throughout the 6 week duration of Phase 2 (maximum dose of 20 mg) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima and the assignment does not change throughout the study.
Escitalopram Pill: Double-blinded, randomly assigned
|
Levomilnacipran Pill (NR)
Participants will receive an initial dose of 20 mg blinded levomilnacipran. At day 7, the doses will be titrated to 40 mg of levomilnacipran. Further titrations (maximum dose of 120 mg of levomilnacipran) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Levomilnacipran Pill: Double-blinded, randomly assigned
|
|---|---|---|---|---|---|---|---|---|
|
Change in Functional Connectivity
Left Middle Frontal Gyrus day 1 difference
|
0.059122257 Z-score
Standard Deviation 0.970768475
|
—
|
-0.337856865 Z-score
Standard Deviation 0.456280057
|
-0.682262788 Z-score
Standard Deviation 0.394139675
|
-0.005553818 Z-score
Standard Deviation 0.336358139
|
—
|
-0.577911771 Z-score
|
—
|
|
Change in Functional Connectivity
Right Middle Frontal Gyrus day 1 difference
|
0.090272305 Z-score
Standard Deviation 1.047858325
|
—
|
0.80863611 Z-score
Standard Deviation 0.591200619
|
-0.064993511 Z-score
Standard Deviation 0.942271068
|
1.243841088 Z-score
Standard Deviation 0.160518864
|
—
|
-1.315813839 Z-score
|
—
|
|
Change in Functional Connectivity
Left Anterior Insular day 1 difference
|
0.007749148 Z-score
Standard Deviation 1.206679758
|
—
|
-0.48413394 Z-score
Standard Deviation 1.3756677
|
-0.224292239 Z-score
Standard Deviation 0.655920209
|
-1.553051837 Z-score
Standard Deviation 0.638678017
|
—
|
0.976927111 Z-score
|
—
|
|
Change in Functional Connectivity
Right Anterior Insular day 1 difference
|
-0.227766723 Z-score
Standard Deviation 1.228475106
|
—
|
-0.23236189 Z-score
Standard Deviation 0.616824453
|
0.147147958 Z-score
Standard Deviation 0.887236616
|
1.056817365 Z-score
Standard Deviation 1.504505678
|
—
|
0.820792593 Z-score
|
—
|
|
Change in Functional Connectivity
Left Amygdala day 1 difference
|
0.259715101 Z-score
Standard Deviation 0.91863688
|
—
|
-0.592134869 Z-score
Standard Deviation 1.3814767
|
0.147597427 Z-score
Standard Deviation 0.599482713
|
-1.33405492 Z-score
Standard Deviation 0.601671616
|
—
|
1.9845321 Z-score
|
—
|
|
Change in Functional Connectivity
Right Amygdala day 1 difference
|
-0.443833224 Z-score
Standard Deviation 1.739580169
|
—
|
-1.311685475 Z-score
Standard Deviation 1.328056717
|
0.548047987 Z-score
Standard Deviation 1.379828096
|
-0.030660361 Z-score
Standard Deviation 0.159008845
|
—
|
0.964444893 Z-score
|
—
|
|
Change in Functional Connectivity
Left prefrontal Anterior Cingulate Cortex day 1 difference
|
0.048557684 Z-score
Standard Deviation 1.079632973
|
—
|
0.735636432 Z-score
Standard Deviation 1.010043826
|
-0.003163926 Z-score
Standard Deviation 0.783815631
|
-0.216753695 Z-score
Standard Deviation 0.608987758
|
—
|
-1.215843301 Z-score
|
—
|
|
Change in Functional Connectivity
Right prefrontal Anterior Cingulate Cortex day 1 difference
|
0.206183452 Z-score
Standard Deviation 1.994469683
|
—
|
1.413900498 Z-score
Standard Deviation 1.543971432
|
0.131919092 Z-score
Standard Deviation 0.80516401
|
0.839416177 Z-score
Standard Deviation 2.093317463
|
—
|
-1.637127786 Z-score
|
—
|
SECONDARY outcome
Timeframe: Baseline, Week 1, and Week 12Population: Participants who completed all 12 weeks of the study with RSQ scores.
The Response Styles Questionnaire- Rumination (RSQ-Rumination) examines propensity towards negative bias during thought. To be used as covariate in functional connectivity analysis. Range of scores: 22-88. Lower the better
Outcome measures
| Measure |
Escitalopram Pill
n=15 Participants
Participants in this arm will receive an initial dose of 5 mg. Further titrations will be decided based on clinical response and tolerability (maximum dose of 20 mg). The medication will be taken by mouth in pill form, once daily.
Escitalopram Pill: Double-blinded, randomly assigned
|
Placebo
n=2 Participants
Participants will be given a sugar pill (placebo) to be taken by mouth once daily for the 6 week duration of Phase I. As this arm is also double-blinded, participants will receive an initial dose of 5 mg and further titrations (maximum dose of 20 mg) will be decided based on clinical response and tolerability.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima.
Placebo: Double-blinded, randomly assigned
|
Escitalopram Pill (Phase II)
n=3 Participants
Participants who were in the placebo arm for Phase I who do not show signs of response to treatment by week 6 (defined as either a MADRS score of greater than 12 or less than a 30% reduction in MADRS score to be deemed a non-responder) will be given the option to have an open-label trial of escitalopram in Phase II.
Participants in this arm will receive an initial dose of 5 mg. Further titrations throughout the 6 week duration of Phase 2 (maximum dose of 20 mg) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima and the assignment does not change throughout the study.
Escitalopram Pill: Double-blinded, randomly assigned
|
Levomilnacipran Pill
n=8 Participants
Participants will receive an initial dose of 20 mg blinded levomilnacipran. At day 7, the doses will be titrated to 40 mg of levomilnacipran. Further titrations (maximum dose of 120 mg of levomilnacipran) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Levomilnacipran Pill: Double-blinded, randomly assigned
|
Escitalopram Pill (NR)
n=2 Participants
Participants in this arm will receive an initial dose of 5 mg. Further titrations will be decided based on clinical response and tolerability (maximum dose of 20 mg). The medication will be taken by mouth in pill form, once daily.
Escitalopram Pill: Double-blinded, randomly assigned
|
Placebo (NR)
Participants will be given a sugar pill (placebo) to be taken by mouth once daily for the 6 week duration of Phase I. As this arm is also double-blinded, participants will receive an initial dose of 5 mg and further titrations (maximum dose of 20 mg) will be decided based on clinical response and tolerability.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima.
|
Escitalopram Pill (NR) (Phase II)
n=1 Participants
Participants who were in the placebo arm for Phase I who do not show signs of response to treatment by week 6 (defined as either a MADRS score of greater than 12 or less than a 30% reduction in MADRS score to be deemed a non-responder) will be given the option to have an open-label trial of escitalopram in Phase II.
Participants in this arm will receive an initial dose of 5 mg. Further titrations throughout the 6 week duration of Phase 2 (maximum dose of 20 mg) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima and the assignment does not change throughout the study.
Escitalopram Pill: Double-blinded, randomly assigned
|
Levomilnacipran Pill (NR)
n=1 Participants
Participants will receive an initial dose of 20 mg blinded levomilnacipran. At day 7, the doses will be titrated to 40 mg of levomilnacipran. Further titrations (maximum dose of 120 mg of levomilnacipran) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Levomilnacipran Pill: Double-blinded, randomly assigned
|
|---|---|---|---|---|---|---|---|---|
|
Response Styles Questionnaire- Rumination (RSQ-Rumination)
Baseline
|
45.1 RSQ total score
Standard Deviation 11.01
|
39.5 RSQ total score
Standard Deviation 3.54
|
60.7 RSQ total score
Standard Deviation 11.15
|
49.7 RSQ total score
Standard Deviation 8.73
|
67.5 RSQ total score
Standard Deviation .071
|
—
|
49 RSQ total score
|
50 RSQ total score
|
|
Response Styles Questionnaire- Rumination (RSQ-Rumination)
Week 01
|
39 RSQ total score
Standard Deviation 11.08
|
40.5 RSQ total score
Standard Deviation 2.12
|
52.3 RSQ total score
Standard Deviation 16.74
|
40.5 RSQ total score
Standard Deviation 7.23
|
61 RSQ total score
Standard Deviation 9.90
|
—
|
46 RSQ total score
|
51 RSQ total score
|
|
Response Styles Questionnaire- Rumination (RSQ-Rumination)
Week 12
|
33.7 RSQ total score
Standard Deviation 10.39
|
28.5 RSQ total score
Standard Deviation 3.54
|
42.7 RSQ total score
Standard Deviation 8.96
|
40.4 RSQ total score
Standard Deviation 9.87
|
60 RSQ total score
Standard Deviation 1.41
|
—
|
30 RSQ total score
|
67 RSQ total score
|
SECONDARY outcome
Timeframe: Baseline, Week 1, and Week 12Population: Participants who completed all 12 weeks of the study with HARS scores.
The Hamilton Anxiety Rating Scale (HARS) is a structured interview to assist in the reliable assessment of anxiety severity by standardizing the method of assessment and providing clear anchor points for the assignment of severity ratings. Examines level of anxiety and somatization. To be used as covariate in functional connectivity analysis. Range of scores: 0-56. Lower the better
Outcome measures
| Measure |
Escitalopram Pill
n=16 Participants
Participants in this arm will receive an initial dose of 5 mg. Further titrations will be decided based on clinical response and tolerability (maximum dose of 20 mg). The medication will be taken by mouth in pill form, once daily.
Escitalopram Pill: Double-blinded, randomly assigned
|
Placebo
n=2 Participants
Participants will be given a sugar pill (placebo) to be taken by mouth once daily for the 6 week duration of Phase I. As this arm is also double-blinded, participants will receive an initial dose of 5 mg and further titrations (maximum dose of 20 mg) will be decided based on clinical response and tolerability.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima.
Placebo: Double-blinded, randomly assigned
|
Escitalopram Pill (Phase II)
n=3 Participants
Participants who were in the placebo arm for Phase I who do not show signs of response to treatment by week 6 (defined as either a MADRS score of greater than 12 or less than a 30% reduction in MADRS score to be deemed a non-responder) will be given the option to have an open-label trial of escitalopram in Phase II.
Participants in this arm will receive an initial dose of 5 mg. Further titrations throughout the 6 week duration of Phase 2 (maximum dose of 20 mg) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima and the assignment does not change throughout the study.
Escitalopram Pill: Double-blinded, randomly assigned
|
Levomilnacipran Pill
n=8 Participants
Participants will receive an initial dose of 20 mg blinded levomilnacipran. At day 7, the doses will be titrated to 40 mg of levomilnacipran. Further titrations (maximum dose of 120 mg of levomilnacipran) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Levomilnacipran Pill: Double-blinded, randomly assigned
|
Escitalopram Pill (NR)
n=2 Participants
Participants in this arm will receive an initial dose of 5 mg. Further titrations will be decided based on clinical response and tolerability (maximum dose of 20 mg). The medication will be taken by mouth in pill form, once daily.
Escitalopram Pill: Double-blinded, randomly assigned
|
Placebo (NR)
Participants will be given a sugar pill (placebo) to be taken by mouth once daily for the 6 week duration of Phase I. As this arm is also double-blinded, participants will receive an initial dose of 5 mg and further titrations (maximum dose of 20 mg) will be decided based on clinical response and tolerability.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima.
|
Escitalopram Pill (NR) (Phase II)
n=1 Participants
Participants who were in the placebo arm for Phase I who do not show signs of response to treatment by week 6 (defined as either a MADRS score of greater than 12 or less than a 30% reduction in MADRS score to be deemed a non-responder) will be given the option to have an open-label trial of escitalopram in Phase II.
Participants in this arm will receive an initial dose of 5 mg. Further titrations throughout the 6 week duration of Phase 2 (maximum dose of 20 mg) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima and the assignment does not change throughout the study.
Escitalopram Pill: Double-blinded, randomly assigned
|
Levomilnacipran Pill (NR)
n=1 Participants
Participants will receive an initial dose of 20 mg blinded levomilnacipran. At day 7, the doses will be titrated to 40 mg of levomilnacipran. Further titrations (maximum dose of 120 mg of levomilnacipran) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Levomilnacipran Pill: Double-blinded, randomly assigned
|
|---|---|---|---|---|---|---|---|---|
|
Hamilton Anxiety Rating Scale (HARS)
Baseline
|
19.3 HARS total score
Standard Deviation 6.66
|
22.5 HARS total score
Standard Deviation 9.19
|
26.6 HARS total score
Standard Deviation 3.05
|
21.5 HARS total score
Standard Deviation 5.26
|
25.5 HARS total score
Standard Deviation 2.12
|
—
|
24 HARS total score
|
23 HARS total score
|
|
Hamilton Anxiety Rating Scale (HARS)
Week 01
|
12.3 HARS total score
Standard Deviation 6.40
|
19.5 HARS total score
Standard Deviation 7.78
|
18.3 HARS total score
Standard Deviation 7.64
|
16.4 HARS total score
Standard Deviation 4.53
|
21.5 HARS total score
Standard Deviation 3.54
|
—
|
17 HARS total score
|
24 HARS total score
|
|
Hamilton Anxiety Rating Scale (HARS)
Week 12
|
7.5 HARS total score
Standard Deviation 5.44
|
7 HARS total score
Standard Deviation 5.66
|
19.7 HARS total score
Standard Deviation 1.53
|
10.6 HARS total score
Standard Deviation 8.33
|
18.5 HARS total score
Standard Deviation 4.95
|
—
|
20 HARS total score
|
32 HARS total score
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: Participants who had complete neuropsychological testing at both Baseline and Week 12.
The neuropsychological testing battery, developed by Co-I Meryl Butters, Ph.D., includes components of the Delis-Kaplan Executive Function Scale (D-KEFS), and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). "dkefs\_trail4\_scaled\_1" is a scaled score for Condition 4 (Number-Letter Switching) of the D-KEFS Trail Making Test, which measures cognitive flexibility and executive functioning. Range 1-19. Higher the better " dkefs\_colorword3\_scaled\_1" is a score from D-KEFS Color-Word Interference. The individual is asked to inhibit an automatic reading response to name the ink color of words that spell out conflicting color names. Range 1-19. Higher the better "rbans\_total\_index\_1" is the total index score from the RBANS, designed to assess various cognitive domains. The total index score is a composite score that provides an overall measure of cognitive functioning by combining the results from all the RBANS subtests. Range 40-155. Higher the better
Outcome measures
| Measure |
Escitalopram Pill
n=10 Participants
Participants in this arm will receive an initial dose of 5 mg. Further titrations will be decided based on clinical response and tolerability (maximum dose of 20 mg). The medication will be taken by mouth in pill form, once daily.
Escitalopram Pill: Double-blinded, randomly assigned
|
Placebo
n=1 Participants
Participants will be given a sugar pill (placebo) to be taken by mouth once daily for the 6 week duration of Phase I. As this arm is also double-blinded, participants will receive an initial dose of 5 mg and further titrations (maximum dose of 20 mg) will be decided based on clinical response and tolerability.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima.
Placebo: Double-blinded, randomly assigned
|
Escitalopram Pill (Phase II)
n=2 Participants
Participants who were in the placebo arm for Phase I who do not show signs of response to treatment by week 6 (defined as either a MADRS score of greater than 12 or less than a 30% reduction in MADRS score to be deemed a non-responder) will be given the option to have an open-label trial of escitalopram in Phase II.
Participants in this arm will receive an initial dose of 5 mg. Further titrations throughout the 6 week duration of Phase 2 (maximum dose of 20 mg) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima and the assignment does not change throughout the study.
Escitalopram Pill: Double-blinded, randomly assigned
|
Levomilnacipran Pill
n=5 Participants
Participants will receive an initial dose of 20 mg blinded levomilnacipran. At day 7, the doses will be titrated to 40 mg of levomilnacipran. Further titrations (maximum dose of 120 mg of levomilnacipran) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Levomilnacipran Pill: Double-blinded, randomly assigned
|
Escitalopram Pill (NR)
Participants in this arm will receive an initial dose of 5 mg. Further titrations will be decided based on clinical response and tolerability (maximum dose of 20 mg). The medication will be taken by mouth in pill form, once daily.
Escitalopram Pill: Double-blinded, randomly assigned
|
Placebo (NR)
Participants will be given a sugar pill (placebo) to be taken by mouth once daily for the 6 week duration of Phase I. As this arm is also double-blinded, participants will receive an initial dose of 5 mg and further titrations (maximum dose of 20 mg) will be decided based on clinical response and tolerability.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima.
|
Escitalopram Pill (NR) (Phase II)
Participants who were in the placebo arm for Phase I who do not show signs of response to treatment by week 6 (defined as either a MADRS score of greater than 12 or less than a 30% reduction in MADRS score to be deemed a non-responder) will be given the option to have an open-label trial of escitalopram in Phase II.
Participants in this arm will receive an initial dose of 5 mg. Further titrations throughout the 6 week duration of Phase 2 (maximum dose of 20 mg) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima and the assignment does not change throughout the study.
Escitalopram Pill: Double-blinded, randomly assigned
|
Levomilnacipran Pill (NR)
Participants will receive an initial dose of 20 mg blinded levomilnacipran. At day 7, the doses will be titrated to 40 mg of levomilnacipran. Further titrations (maximum dose of 120 mg of levomilnacipran) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Levomilnacipran Pill: Double-blinded, randomly assigned
|
|---|---|---|---|---|---|---|---|---|
|
Neuropsychological Evaluations
dkefs_trail4_scaled_1_Baseline
|
11 score on a scale
Standard Deviation 3.71
|
11 score on a scale
|
8 score on a scale
Standard Deviation 5.66
|
10.6 score on a scale
Standard Deviation 3.21
|
—
|
—
|
—
|
—
|
|
Neuropsychological Evaluations
dkefs_trail4_scaled_1_Week12
|
10.8 score on a scale
Standard Deviation 3.65
|
11 score on a scale
|
9 score on a scale
Standard Deviation 4.24
|
12.25 score on a scale
Standard Deviation 1.26
|
—
|
—
|
—
|
—
|
|
Neuropsychological Evaluations
dkefs_colorword3_scaled_1_Baseline
|
11 score on a scale
Standard Deviation 3.26
|
9 score on a scale
|
9 score on a scale
Standard Deviation 0
|
11 score on a scale
Standard Deviation 2.00
|
—
|
—
|
—
|
—
|
|
Neuropsychological Evaluations
dkefs_colorword3_scaled_1_Week12
|
11.6 score on a scale
Standard Deviation 2.50
|
9 score on a scale
|
10.5 score on a scale
Standard Deviation 0.71
|
10.6 score on a scale
Standard Deviation 3.58
|
—
|
—
|
—
|
—
|
|
Neuropsychological Evaluations
rbans_total_index_1_Baseline
|
97.4 score on a scale
Standard Deviation 9.21
|
110 score on a scale
|
94 score on a scale
Standard Deviation 1.41
|
103.2 score on a scale
Standard Deviation 17.92
|
—
|
—
|
—
|
—
|
|
Neuropsychological Evaluations
rbans_total_index_1_Week12
|
102.9 score on a scale
Standard Deviation 12.04
|
107 score on a scale
|
102.5 score on a scale
Standard Deviation 2.12
|
102.6 score on a scale
Standard Deviation 20.41
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: BaselinePopulation: The Outcome are those who were considered "responders" for this study. No participants in the Placebo group had previously taken an antidepressant.
Investigators will examine prior treatment history and how this may affect treatment response in this study. Number of participants analyzed are those who have previously had a trial of at least one antidepressant.
Outcome measures
| Measure |
Escitalopram Pill
n=9 Participants
Participants in this arm will receive an initial dose of 5 mg. Further titrations will be decided based on clinical response and tolerability (maximum dose of 20 mg). The medication will be taken by mouth in pill form, once daily.
Escitalopram Pill: Double-blinded, randomly assigned
|
Placebo
Participants will be given a sugar pill (placebo) to be taken by mouth once daily for the 6 week duration of Phase I. As this arm is also double-blinded, participants will receive an initial dose of 5 mg and further titrations (maximum dose of 20 mg) will be decided based on clinical response and tolerability.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima.
Placebo: Double-blinded, randomly assigned
|
Escitalopram Pill (Phase II)
n=2 Participants
Participants who were in the placebo arm for Phase I who do not show signs of response to treatment by week 6 (defined as either a MADRS score of greater than 12 or less than a 30% reduction in MADRS score to be deemed a non-responder) will be given the option to have an open-label trial of escitalopram in Phase II.
Participants in this arm will receive an initial dose of 5 mg. Further titrations throughout the 6 week duration of Phase 2 (maximum dose of 20 mg) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima and the assignment does not change throughout the study.
Escitalopram Pill: Double-blinded, randomly assigned
|
Levomilnacipran Pill
n=3 Participants
Participants will receive an initial dose of 20 mg blinded levomilnacipran. At day 7, the doses will be titrated to 40 mg of levomilnacipran. Further titrations (maximum dose of 120 mg of levomilnacipran) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Levomilnacipran Pill: Double-blinded, randomly assigned
|
Escitalopram Pill (NR)
Participants in this arm will receive an initial dose of 5 mg. Further titrations will be decided based on clinical response and tolerability (maximum dose of 20 mg). The medication will be taken by mouth in pill form, once daily.
Escitalopram Pill: Double-blinded, randomly assigned
|
Placebo (NR)
Participants will be given a sugar pill (placebo) to be taken by mouth once daily for the 6 week duration of Phase I. As this arm is also double-blinded, participants will receive an initial dose of 5 mg and further titrations (maximum dose of 20 mg) will be decided based on clinical response and tolerability.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima.
|
Escitalopram Pill (NR) (Phase II)
Participants who were in the placebo arm for Phase I who do not show signs of response to treatment by week 6 (defined as either a MADRS score of greater than 12 or less than a 30% reduction in MADRS score to be deemed a non-responder) will be given the option to have an open-label trial of escitalopram in Phase II.
Participants in this arm will receive an initial dose of 5 mg. Further titrations throughout the 6 week duration of Phase 2 (maximum dose of 20 mg) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima and the assignment does not change throughout the study.
Escitalopram Pill: Double-blinded, randomly assigned
|
Levomilnacipran Pill (NR)
Participants will receive an initial dose of 20 mg blinded levomilnacipran. At day 7, the doses will be titrated to 40 mg of levomilnacipran. Further titrations (maximum dose of 120 mg of levomilnacipran) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Levomilnacipran Pill: Double-blinded, randomly assigned
|
|---|---|---|---|---|---|---|---|---|
|
Antidepressant Treatment History Questionnaire (ATHF)
|
7 Participants
|
0 Participants
|
1 Participants
|
2 Participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Weeks 1-12Population: Analyses will not be performed at any time in the future.
Investigators will assess how blood levels of escitalopram and levomilnacipran may affect treatment response. The data was not collected because the Co-Investigator responsible for the analyses left academia and the University of Pittsburgh. No data will ever be produced and there will be no results to report.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: BaselinePopulation: Age of onset for current depressive episode and how it relates treatment outcome.
Investigators will assess how early vs. late onset depression (e.g., onset before/after age 60) may affect treatment response.
Outcome measures
| Measure |
Escitalopram Pill
n=16 Participants
Participants in this arm will receive an initial dose of 5 mg. Further titrations will be decided based on clinical response and tolerability (maximum dose of 20 mg). The medication will be taken by mouth in pill form, once daily.
Escitalopram Pill: Double-blinded, randomly assigned
|
Placebo
n=2 Participants
Participants will be given a sugar pill (placebo) to be taken by mouth once daily for the 6 week duration of Phase I. As this arm is also double-blinded, participants will receive an initial dose of 5 mg and further titrations (maximum dose of 20 mg) will be decided based on clinical response and tolerability.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima.
Placebo: Double-blinded, randomly assigned
|
Escitalopram Pill (Phase II)
n=3 Participants
Participants who were in the placebo arm for Phase I who do not show signs of response to treatment by week 6 (defined as either a MADRS score of greater than 12 or less than a 30% reduction in MADRS score to be deemed a non-responder) will be given the option to have an open-label trial of escitalopram in Phase II.
Participants in this arm will receive an initial dose of 5 mg. Further titrations throughout the 6 week duration of Phase 2 (maximum dose of 20 mg) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima and the assignment does not change throughout the study.
Escitalopram Pill: Double-blinded, randomly assigned
|
Levomilnacipran Pill
n=6 Participants
Participants will receive an initial dose of 20 mg blinded levomilnacipran. At day 7, the doses will be titrated to 40 mg of levomilnacipran. Further titrations (maximum dose of 120 mg of levomilnacipran) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Levomilnacipran Pill: Double-blinded, randomly assigned
|
Escitalopram Pill (NR)
n=2 Participants
Participants in this arm will receive an initial dose of 5 mg. Further titrations will be decided based on clinical response and tolerability (maximum dose of 20 mg). The medication will be taken by mouth in pill form, once daily.
Escitalopram Pill: Double-blinded, randomly assigned
|
Placebo (NR)
Participants will be given a sugar pill (placebo) to be taken by mouth once daily for the 6 week duration of Phase I. As this arm is also double-blinded, participants will receive an initial dose of 5 mg and further titrations (maximum dose of 20 mg) will be decided based on clinical response and tolerability.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima.
|
Escitalopram Pill (NR) (Phase II)
Participants who were in the placebo arm for Phase I who do not show signs of response to treatment by week 6 (defined as either a MADRS score of greater than 12 or less than a 30% reduction in MADRS score to be deemed a non-responder) will be given the option to have an open-label trial of escitalopram in Phase II.
Participants in this arm will receive an initial dose of 5 mg. Further titrations throughout the 6 week duration of Phase 2 (maximum dose of 20 mg) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima and the assignment does not change throughout the study.
Escitalopram Pill: Double-blinded, randomly assigned
|
Levomilnacipran Pill (NR)
n=1 Participants
Participants will receive an initial dose of 20 mg blinded levomilnacipran. At day 7, the doses will be titrated to 40 mg of levomilnacipran. Further titrations (maximum dose of 120 mg of levomilnacipran) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Levomilnacipran Pill: Double-blinded, randomly assigned
|
|---|---|---|---|---|---|---|---|---|
|
Age of Onset
Number of participants age of onset before age 60
|
6 Participants
|
2 Participants
|
2 Participants
|
2 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Age of Onset
Number of participants age of onset at or after age 60
|
10 Participants
|
0 Participants
|
1 Participants
|
4 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: Duration of illness at BaselinePopulation: Number of participants analyzed if information was available during interviews
Investigators will assess how length of current episode affect treatment response.
Outcome measures
| Measure |
Escitalopram Pill
n=16 Participants
Participants in this arm will receive an initial dose of 5 mg. Further titrations will be decided based on clinical response and tolerability (maximum dose of 20 mg). The medication will be taken by mouth in pill form, once daily.
Escitalopram Pill: Double-blinded, randomly assigned
|
Placebo
n=2 Participants
Participants will be given a sugar pill (placebo) to be taken by mouth once daily for the 6 week duration of Phase I. As this arm is also double-blinded, participants will receive an initial dose of 5 mg and further titrations (maximum dose of 20 mg) will be decided based on clinical response and tolerability.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima.
Placebo: Double-blinded, randomly assigned
|
Escitalopram Pill (Phase II)
n=3 Participants
Participants who were in the placebo arm for Phase I who do not show signs of response to treatment by week 6 (defined as either a MADRS score of greater than 12 or less than a 30% reduction in MADRS score to be deemed a non-responder) will be given the option to have an open-label trial of escitalopram in Phase II.
Participants in this arm will receive an initial dose of 5 mg. Further titrations throughout the 6 week duration of Phase 2 (maximum dose of 20 mg) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima and the assignment does not change throughout the study.
Escitalopram Pill: Double-blinded, randomly assigned
|
Levomilnacipran Pill
n=6 Participants
Participants will receive an initial dose of 20 mg blinded levomilnacipran. At day 7, the doses will be titrated to 40 mg of levomilnacipran. Further titrations (maximum dose of 120 mg of levomilnacipran) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Levomilnacipran Pill: Double-blinded, randomly assigned
|
Escitalopram Pill (NR)
n=2 Participants
Participants in this arm will receive an initial dose of 5 mg. Further titrations will be decided based on clinical response and tolerability (maximum dose of 20 mg). The medication will be taken by mouth in pill form, once daily.
Escitalopram Pill: Double-blinded, randomly assigned
|
Placebo (NR)
Participants will be given a sugar pill (placebo) to be taken by mouth once daily for the 6 week duration of Phase I. As this arm is also double-blinded, participants will receive an initial dose of 5 mg and further titrations (maximum dose of 20 mg) will be decided based on clinical response and tolerability.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima.
|
Escitalopram Pill (NR) (Phase II)
Participants who were in the placebo arm for Phase I who do not show signs of response to treatment by week 6 (defined as either a MADRS score of greater than 12 or less than a 30% reduction in MADRS score to be deemed a non-responder) will be given the option to have an open-label trial of escitalopram in Phase II.
Participants in this arm will receive an initial dose of 5 mg. Further titrations throughout the 6 week duration of Phase 2 (maximum dose of 20 mg) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima and the assignment does not change throughout the study.
Escitalopram Pill: Double-blinded, randomly assigned
|
Levomilnacipran Pill (NR)
n=1 Participants
Participants will receive an initial dose of 20 mg blinded levomilnacipran. At day 7, the doses will be titrated to 40 mg of levomilnacipran. Further titrations (maximum dose of 120 mg of levomilnacipran) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Levomilnacipran Pill: Double-blinded, randomly assigned
|
|---|---|---|---|---|---|---|---|---|
|
Duration of Illness
Duration of one year or less
|
6 Participants
|
0 Participants
|
1 Participants
|
3 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
1 Participants
|
|
Duration of Illness
Duration of more than one year to 10 years
|
5 Participants
|
0 Participants
|
0 Participants
|
2 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Duration of Illness
Duration of more than 10 years
|
5 Participants
|
2 Participants
|
2 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
Escitalopram Pill
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
Levomilnacipran Pill
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Escitalopram Pill (Phase II)
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Escitalopram Pill
n=25 participants at risk
Participants in this arm will receive an initial dose of 5 mg. Further titrations will be decided based on clinical response and tolerability (maximum dose of 20 mg). The medication will be taken by mouth in pill form, once daily.
Escitalopram Pill: Double-blinded, randomly assigned
|
Levomilnacipran Pill
n=22 participants at risk
Participants will receive an initial dose of 20 mg blinded levomilnacipran. At day 7, the doses will be titrated to 40 mg of levomilnacipran. Further titrations (maximum dose of 120 mg of levomilnacipran) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Levomilnacipran Pill: Double-blinded, randomly assigned
|
Placebo
n=4 participants at risk
Participants will be given a sugar pill (placebo) to be taken by mouth once daily for the 6 week duration of Phase I. As this arm is also double-blinded, participants will receive an initial dose of 5 mg and further titrations (maximum dose of 20 mg) will be decided based on clinical response and tolerability.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima.
|
Escitalopram Pill (Phase II)
n=6 participants at risk
Participants who were in the placebo arm for Phase I who do not show signs of response to treatment by week 6 (defined as either a MADRS score of greater than 12 or less than a 30% reduction in MADRS score to be deemed a non-responder) will be given the option to have an open-label trial of escitalopram in Phase II.
Participants in this arm will receive an initial dose of 5 mg. Further titrations throughout the 6 week duration of Phase 2 (maximum dose of 20 mg) will be decided based on clinical response and tolerability. The medication will be taken by mouth in pill form, once daily.
Note: This arm no longer applies as of 5/16/18. Participants are now randomly assigned to Lexapro or Fetzima and the assignment does not change throughout the study.
Escitalopram Pill: Double-blinded, randomly assigned
|
|---|---|---|---|---|
|
Psychiatric disorders
anxiety
|
8.0%
2/25 • Number of events 2 • 12 weeks
|
0.00%
0/22 • 12 weeks
|
0.00%
0/4 • 12 weeks
|
0.00%
0/6 • 12 weeks
|
|
Eye disorders
blurred vision
|
12.0%
3/25 • Number of events 3 • 12 weeks
|
0.00%
0/22 • 12 weeks
|
0.00%
0/4 • 12 weeks
|
16.7%
1/6 • Number of events 1 • 12 weeks
|
|
Gastrointestinal disorders
constipation
|
20.0%
5/25 • Number of events 5 • 12 weeks
|
18.2%
4/22 • Number of events 4 • 12 weeks
|
0.00%
0/4 • 12 weeks
|
16.7%
1/6 • Number of events 1 • 12 weeks
|
|
Metabolism and nutrition disorders
decreased appetite
|
12.0%
3/25 • Number of events 3 • 12 weeks
|
13.6%
3/22 • Number of events 3 • 12 weeks
|
0.00%
0/4 • 12 weeks
|
16.7%
1/6 • Number of events 1 • 12 weeks
|
|
Gastrointestinal disorders
diarrhea
|
12.0%
3/25 • Number of events 3 • 12 weeks
|
13.6%
3/22 • Number of events 3 • 12 weeks
|
0.00%
0/4 • 12 weeks
|
33.3%
2/6 • Number of events 2 • 12 weeks
|
|
General disorders
drowsiness or yawning
|
40.0%
10/25 • Number of events 16 • 12 weeks
|
9.1%
2/22 • Number of events 3 • 12 weeks
|
0.00%
0/4 • 12 weeks
|
50.0%
3/6 • Number of events 3 • 12 weeks
|
|
General disorders
dry mouth
|
24.0%
6/25 • Number of events 6 • 12 weeks
|
13.6%
3/22 • Number of events 3 • 12 weeks
|
0.00%
0/4 • 12 weeks
|
33.3%
2/6 • Number of events 2 • 12 weeks
|
|
Nervous system disorders
extrapyramidal symptoms
|
12.0%
3/25 • Number of events 4 • 12 weeks
|
4.5%
1/22 • Number of events 1 • 12 weeks
|
0.00%
0/4 • 12 weeks
|
33.3%
2/6 • Number of events 2 • 12 weeks
|
|
Gastrointestinal disorders
flatulence
|
0.00%
0/25 • 12 weeks
|
9.1%
2/22 • Number of events 2 • 12 weeks
|
0.00%
0/4 • 12 weeks
|
0.00%
0/6 • 12 weeks
|
|
General disorders
headache
|
28.0%
7/25 • Number of events 7 • 12 weeks
|
22.7%
5/22 • Number of events 5 • 12 weeks
|
0.00%
0/4 • 12 weeks
|
33.3%
2/6 • Number of events 2 • 12 weeks
|
|
General disorders
heartburn
|
4.0%
1/25 • Number of events 1 • 12 weeks
|
4.5%
1/22 • Number of events 1 • 12 weeks
|
0.00%
0/4 • 12 weeks
|
0.00%
0/6 • 12 weeks
|
|
Metabolism and nutrition disorders
increased appetite
|
12.0%
3/25 • Number of events 3 • 12 weeks
|
9.1%
2/22 • Number of events 2 • 12 weeks
|
0.00%
0/4 • 12 weeks
|
0.00%
0/6 • 12 weeks
|
|
General disorders
increased body temperature/sweating
|
20.0%
5/25 • Number of events 6 • 12 weeks
|
9.1%
2/22 • Number of events 3 • 12 weeks
|
0.00%
0/4 • 12 weeks
|
16.7%
1/6 • Number of events 1 • 12 weeks
|
|
Psychiatric disorders
increased irritability
|
4.0%
1/25 • Number of events 1 • 12 weeks
|
4.5%
1/22 • Number of events 1 • 12 weeks
|
0.00%
0/4 • 12 weeks
|
0.00%
0/6 • 12 weeks
|
|
General disorders
increased sleep
|
0.00%
0/25 • 12 weeks
|
0.00%
0/22 • 12 weeks
|
0.00%
0/4 • 12 weeks
|
33.3%
2/6 • Number of events 2 • 12 weeks
|
|
General disorders
insomnia or trouble sleeping
|
32.0%
8/25 • Number of events 8 • 12 weeks
|
18.2%
4/22 • Number of events 4 • 12 weeks
|
0.00%
0/4 • 12 weeks
|
33.3%
2/6 • Number of events 2 • 12 weeks
|
|
General disorders
lightheadedness
|
20.0%
5/25 • Number of events 7 • 12 weeks
|
22.7%
5/22 • Number of events 6 • 12 weeks
|
0.00%
0/4 • 12 weeks
|
0.00%
0/6 • 12 weeks
|
|
General disorders
nausea or vomiting
|
24.0%
6/25 • Number of events 7 • 12 weeks
|
22.7%
5/22 • Number of events 5 • 12 weeks
|
0.00%
0/4 • 12 weeks
|
33.3%
2/6 • Number of events 2 • 12 weeks
|
|
Cardiac disorders
palpitations
|
4.0%
1/25 • Number of events 1 • 12 weeks
|
4.5%
1/22 • Number of events 1 • 12 weeks
|
0.00%
0/4 • 12 weeks
|
0.00%
0/6 • 12 weeks
|
|
Skin and subcutaneous tissue disorders
rash/itching
|
0.00%
0/25 • 12 weeks
|
4.5%
1/22 • Number of events 1 • 12 weeks
|
0.00%
0/4 • 12 weeks
|
16.7%
1/6 • Number of events 1 • 12 weeks
|
|
Renal and urinary disorders
uninary problems
|
8.0%
2/25 • Number of events 3 • 12 weeks
|
13.6%
3/22 • Number of events 4 • 12 weeks
|
0.00%
0/4 • 12 weeks
|
0.00%
0/6 • 12 weeks
|
|
General disorders
vertigo
|
8.0%
2/25 • Number of events 2 • 12 weeks
|
4.5%
1/22 • Number of events 1 • 12 weeks
|
0.00%
0/4 • 12 weeks
|
0.00%
0/6 • 12 weeks
|
|
General disorders
weight gain
|
8.0%
2/25 • Number of events 2 • 12 weeks
|
4.5%
1/22 • Number of events 1 • 12 weeks
|
0.00%
0/4 • 12 weeks
|
16.7%
1/6 • Number of events 1 • 12 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place