Trial Outcomes & Findings for A Study of Patients With Major Depressive Disorder and Residual Apathy (NCT NCT00985504)

Last Updated: 2011-12-13

Results Overview

The AES-C is a validated 18-item instrument used to assess cognitive, behavioral, emotional and other symptoms of apathy. Clinicians rate each item based on verbal and nonverbal information provided by the participant. Item scores range from 1 (not at all characteristic) to 4 (a lot characteristic). Total scores range from 18 to 72 where higher derived scores indicate more severe apathy. The Least Squares (LS) Mean Value was calculated from a mixed model repeated measures (MMRM) model with terms of treatment, pooled investigator, visit, treatment\*visit, baseline, and baseline\*visit.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

483 participants

Primary outcome timeframe

Baseline, 8 weeks

Results posted on

2011-12-13

Participant Flow

Acute treatment period (1 week): Participants randomized to switch to 60 milligrams (mg) duloxetine once daily (QD) by mouth (po) or 10 mg escitalopram QD po. Optimization period (7 weeks): Participants given duloxetine or escitalopram in acute study period may optimize their QD po doses (60-120 mg duloxetine QD po; 10-20 mg escitalopram QD po).

Participant milestones

Participant milestones
Measure	Duloxetine Participants received 60 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week (Acute Treatment Period) followed by 60-120 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.	Escitalopram Participants received 10 mg of escitalopram QD po for 1 week (Acute Treatment Period) followed by 10-20 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.
Acute Treatment Period STARTED	244	239
Acute Treatment Period COMPLETED	229	227
Acute Treatment Period NOT COMPLETED	15	12
Optimization Period STARTED	229	227
Optimization Period COMPLETED	203	204
Optimization Period NOT COMPLETED	26	23

Reasons for withdrawal

Reasons for withdrawal
Measure	Duloxetine Participants received 60 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week (Acute Treatment Period) followed by 60-120 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.	Escitalopram Participants received 10 mg of escitalopram QD po for 1 week (Acute Treatment Period) followed by 10-20 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.
Acute Treatment Period Adverse Event	3	4
Acute Treatment Period Entry Criteria Not Met	1	2
Acute Treatment Period Protocol Violation	2	0
Acute Treatment Period Sponsor Decision	0	1
Acute Treatment Period Withdrawal by Subject	9	5
Optimization Period Adverse Event	7	9
Optimization Period Death	0	1
Optimization Period Lack of Efficacy	5	3
Optimization Period Lost to Follow-up	0	1
Optimization Period Physician Decision	1	0
Optimization Period Protocol Violation	3	1
Optimization Period Withdrawal by Subject	10	8

Baseline Characteristics

A Study of Patients With Major Depressive Disorder and Residual Apathy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Duloxetine n=244 Participants Participants received 60 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week (Acute Treatment Period) followed by 60-120 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.	Escitalopram n=239 Participants Participants received 10 mg of escitalopram QD po for 1 week (Acute Treatment Period) followed by 10-20 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.	Total n=483 Participants Total of all reporting groups
Age Continuous	44.15 years STANDARD_DEVIATION 13.81 • n=5 Participants	44.93 years STANDARD_DEVIATION 12.89 • n=7 Participants	44.54 years STANDARD_DEVIATION 13.35 • n=5 Participants
Sex: Female, Male Female	187 Participants n=5 Participants	179 Participants n=7 Participants	366 Participants n=5 Participants
Sex: Female, Male Male	57 Participants n=5 Participants	60 Participants n=7 Participants	117 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	45 Participants n=5 Participants	44 Participants n=7 Participants	89 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	199 Participants n=5 Participants	195 Participants n=7 Participants	394 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	34 participants n=5 Participants	37 participants n=7 Participants	71 participants n=5 Participants
Race (NIH/OMB) Asian	90 participants n=5 Participants	82 participants n=7 Participants	172 participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Race (NIH/OMB) Black or African American	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Race (NIH/OMB) White	120 participants n=5 Participants	119 participants n=7 Participants	239 participants n=5 Participants
Race (NIH/OMB) More than one race	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants
Region of Enrollment Australia	24 participants n=5 Participants	25 participants n=7 Participants	49 participants n=5 Participants
Region of Enrollment Canada	44 participants n=5 Participants	43 participants n=7 Participants	87 participants n=5 Participants
Region of Enrollment China	47 participants n=5 Participants	41 participants n=7 Participants	88 participants n=5 Participants
Region of Enrollment Italy	23 participants n=5 Participants	22 participants n=7 Participants	45 participants n=5 Participants
Region of Enrollment Korea, Republic of	18 participants n=5 Participants	15 participants n=7 Participants	33 participants n=5 Participants
Region of Enrollment Mexico	42 participants n=5 Participants	43 participants n=7 Participants	85 participants n=5 Participants
Region of Enrollment Russian Federation	23 participants n=5 Participants	25 participants n=7 Participants	48 participants n=5 Participants
Region of Enrollment Taiwan	23 participants n=5 Participants	25 participants n=7 Participants	48 participants n=5 Participants
Taking Escitalopram 3 Months Prior to Study Entry Yes	67 participants n=5 Participants	59 participants n=7 Participants	126 participants n=5 Participants
Taking Escitalopram 3 Months Prior to Study Entry No	177 participants n=5 Participants	180 participants n=7 Participants	357 participants n=5 Participants
Apathy Evaluation Scale - Clinician Rated Version (AES-C) Total Score	46.28 units on a scale STANDARD_DEVIATION 7.82 • n=5 Participants	46.34 units on a scale STANDARD_DEVIATION 8.14 • n=7 Participants	46.31 units on a scale STANDARD_DEVIATION 7.97 • n=5 Participants
Montgomery-Asberg Depression Rating Scale (MADRS) Total Score	10.57 units on a scale STANDARD_DEVIATION 3.49 • n=5 Participants	10.29 units on a scale STANDARD_DEVIATION 3.68 • n=7 Participants	10.43 units on a scale STANDARD_DEVIATION 3.59 • n=5 Participants
Montgomery-Asberg Depression Rating Scale (MADRS) Item 8 Score	1.82 units on a scale STANDARD_DEVIATION 1.10 • n=5 Participants	1.82 units on a scale STANDARD_DEVIATION 1.15 • n=7 Participants	1.82 units on a scale STANDARD_DEVIATION 1.13 • n=5 Participants
Clinical Global Impressions of Severity Scale (CGI-S)	3.05 units on a scale STANDARD_DEVIATION 0.91 • n=5 Participants	3.04 units on a scale STANDARD_DEVIATION 0.91 • n=7 Participants	3.05 units on a scale STANDARD_DEVIATION 0.91 • n=5 Participants
Rothschild Scale for Antidepressant Tachyphylaxis (RSAT) Total Score	10.72 units on a scale STANDARD_DEVIATION 4.92 • n=5 Participants	10.51 units on a scale STANDARD_DEVIATION 4.95 • n=7 Participants	10.62 units on a scale STANDARD_DEVIATION 4.93 • n=5 Participants
The Massachusetts General Hospital Cognitive and Physical functioning Questionnaire (MGH-CPFQ) Total	24.78 units on a scale STANDARD_DEVIATION 5.73 • n=5 Participants	24.69 units on a scale STANDARD_DEVIATION 5.83 • n=7 Participants	24.73 units on a scale STANDARD_DEVIATION 5.78 • n=5 Participants
Sheehan Disability Scale - Total Score (SDS Total)	15.32 units on a scale STANDARD_DEVIATION 6.76 • n=5 Participants	14.62 units on a scale STANDARD_DEVIATION 6.39 • n=7 Participants	14.98 units on a scale STANDARD_DEVIATION 6.58 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 8 weeks

Population: All randomized participants with a baseline and at least 1 post-baseline result.

Outcome measures

Outcome measures
Measure	Duloxetine n=213 Participants Participants received 60 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week (Acute Treatment Period) followed by 60-120 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.	Escitalopram n=210 Participants Participants received 10 mg of escitalopram QD po for 1 week (Acute Treatment Period) followed by 10-20 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.
Change From Baseline in the Apathy Evaluation Scale - Clinician Rated Version (AES-C) Total Score at Week 8	-13.88 units on a scale Standard Error 0.54	-13.50 units on a scale Standard Error 0.54

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: All randomized participants with a baseline and at least 1 post-baseline result.

AES-C subscales separately assess participants' intensity of cognitive, behavioral, emotional, and other apathy symptoms with individual item scores of 1 (not at all characteristic) to 4 (a lot characteristic). Subtotal score ranges for the subscales are: 8-32 (cognitive), 5-20 (behavioral), 2-8 (emotional), and 3-12 for other (display of personal insight, initiative and motivation). Higher subscale scores indicate greater illness severity. The LS Mean Value was calculated from an MMRM model with terms of treatment, pooled investigator, visit, treatment\*visit, baseline, and baseline\*visit.

Outcome measures

Outcome measures
Measure	Duloxetine n=213 Participants Participants received 60 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week (Acute Treatment Period) followed by 60-120 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.	Escitalopram n=210 Participants Participants received 10 mg of escitalopram QD po for 1 week (Acute Treatment Period) followed by 10-20 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.
Change From Baseline in the Apathy Evaluation Scale-Clinician Rated Version (AES-C) Subscale Scores at Week 8 Cognition Items Total Score	-6.49 units on a scale Standard Error 0.26	-6.25 units on a scale Standard Error 0.26
Change From Baseline in the Apathy Evaluation Scale-Clinician Rated Version (AES-C) Subscale Scores at Week 8 Behavior Items Total Score	-3.35 units on a scale Standard Error 0.15	-3.25 units on a scale Standard Error 0.16
Change From Baseline in the Apathy Evaluation Scale-Clinician Rated Version (AES-C) Subscale Scores at Week 8 Emotional Items Total Score	-1.66 units on a scale Standard Error 0.08	-1.58 units on a scale Standard Error 0.08
Change From Baseline in the Apathy Evaluation Scale-Clinician Rated Version (AES-C) Subscale Scores at Week 8 Other Items Total Score	-2.43 units on a scale Standard Error 0.10	-2.44 units on a scale Standard Error 0.10

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: All randomized participants with a baseline at and least 1 post-baseline result.

RSAT assesses symptoms of apathy or decreased motivation among depressed participants who have achieved symptomatic remission with antidepressant treatment and consists of 6 self-report items assessing energy level, motivation and interest, cognitive functioning, weight gain, sleep and sexual functioning, as well as affect. Each item score ranges from 0 to 4 with total scores ranging from 0 to 28. Higher scores indicate greater disease severity. LS Mean Value was calculated from an MMRM model with terms of treatment, pooled investigator, visit, treatment\*visit, baseline, and baseline\*visit.

Outcome measures

Outcome measures
Measure	Duloxetine n=212 Participants Participants received 60 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week (Acute Treatment Period) followed by 60-120 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.	Escitalopram n=210 Participants Participants received 10 mg of escitalopram QD po for 1 week (Acute Treatment Period) followed by 10-20 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.
Change From Baseline in the Rothschild Scale for Antidepressant Tachyphylaxis (RSAT) Total and Individual Item Scores at Week 8 RSAT Total Score	-5.50 units on a scale Standard Error 0.26	-4.98 units on a scale Standard Error 0.26
Change From Baseline in the Rothschild Scale for Antidepressant Tachyphylaxis (RSAT) Total and Individual Item Scores at Week 8 Energy Level	-1.33 units on a scale Standard Error 0.07	-1.19 units on a scale Standard Error 0.07
Change From Baseline in the Rothschild Scale for Antidepressant Tachyphylaxis (RSAT) Total and Individual Item Scores at Week 8 Motivation and Interest	-1.41 units on a scale Standard Error 0.06	-1.29 units on a scale Standard Error 0.06
Change From Baseline in the Rothschild Scale for Antidepressant Tachyphylaxis (RSAT) Total and Individual Item Scores at Week 8 Cognitive Functioning	-0.90 units on a scale Standard Error 0.06	-0.80 units on a scale Standard Error 0.06
Change From Baseline in the Rothschild Scale for Antidepressant Tachyphylaxis (RSAT) Total and Individual Item Scores at Week 8 Weight Gain	-0.25 units on a scale Standard Error 0.05	-0.11 units on a scale Standard Error 0.05
Change From Baseline in the Rothschild Scale for Antidepressant Tachyphylaxis (RSAT) Total and Individual Item Scores at Week 8 Sleep	-0.48 units on a scale Standard Error 0.08	-0.55 units on a scale Standard Error 0.08
Change From Baseline in the Rothschild Scale for Antidepressant Tachyphylaxis (RSAT) Total and Individual Item Scores at Week 8 Sexual Functioning	-0.62 units on a scale Standard Error 0.07	-0.60 units on a scale Standard Error 0.07
Change From Baseline in the Rothschild Scale for Antidepressant Tachyphylaxis (RSAT) Total and Individual Item Scores at Week 8 Affect	-0.53 units on a scale Standard Error 0.04	-0.50 units on a scale Standard Error 0.04

SECONDARY outcome

Timeframe: 8 weeks

Population: All randomized participants.

The PGI-I is a scale that measures the participant's perception of improvement at the time of assessment compared with the start of treatment. The score ranges from 1 (very much better) to 7 (very much worse). The LS Mean Value was calculated from an MMRM model with terms of treatment, pooled investigator, visit, and treatment\*visit.

Outcome measures

Outcome measures
Measure	Duloxetine n=213 Participants Participants received 60 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week (Acute Treatment Period) followed by 60-120 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.	Escitalopram n=210 Participants Participants received 10 mg of escitalopram QD po for 1 week (Acute Treatment Period) followed by 10-20 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.
Patient's Global Impressions of Improvement Scale (PGI-I) Rating Scale Score at Week 8	2.59 units on a scale Standard Error 0.08	2.55 units on a scale Standard Error 0.08

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: All randomized participants with a baseline and at least 1 post-baseline result.

The CGI-S measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). The LS Mean Value was calculated from an MMRM model with terms of treatment, pooled investigator, visit, treatment\*visit, baseline, and baseline\*visit.

Outcome measures

Outcome measures
Measure	Duloxetine n=213 Participants Participants received 60 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week (Acute Treatment Period) followed by 60-120 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.	Escitalopram n=210 Participants Participants received 10 mg of escitalopram QD po for 1 week (Acute Treatment Period) followed by 10-20 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.
Change From Baseline in the Clinical Global Impression of Severity (CGI-S) Rating Scale at Week 8	-0.86 units on a scale Standard Error 0.06	-0.93 units on a scale Standard Error 0.06

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: All randomized participants with a baseline and at least 1 post-baseline result.

MADRS is a rating scale for severity of depressive mood symptoms and has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Item 8 assesses the participant's inability to feel. Scores range from 0 (normal interest in surroundings and other people) to 6 (emotional paralysis, inability to feel anger/grief/pleasure). The LS Mean Value was calculated from an MMRM model with terms of treatment, pooled investigator, visit, treatment\*visit, baseline, and baseline\*visit.

Outcome measures

Outcome measures
Measure	Duloxetine n=213 Participants Participants received 60 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week (Acute Treatment Period) followed by 60-120 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.	Escitalopram n=210 Participants Participants received 10 mg of escitalopram QD po for 1 week (Acute Treatment Period) followed by 10-20 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.
Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Item 8 (Inability to Feel) at Week 8 Total Score	-4.21 units on a scale Standard Error 0.32	-4.14 units on a scale Standard Error 0.33
Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Item 8 (Inability to Feel) at Week 8 Item 8 (Inability to Feel)	-1.01 units on a scale Standard Error 0.06	-0.90 units on a scale Standard Error 0.06

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: All randomized participants with a baseline and at least 1 post-baseline result.

The MGH-CPFQ is a 7-item participant-rated questionnaire evaluating the participant's cognitive and physical well-being during the past month. The MGH-CPFQ assesses motivation, wakefulness, energy, focus, recall, word-finding difficulty, and mental acuity. Each item is scored on a 6-point scale ranging from 1 ("greater than normal") to 2 ("normal") to 6 ("totally absent"). Total scores range from 7 to 42. Higher scores indicate greater disease severity. The LS Mean Value was calculated from an analysis of covariance (ANCOVA) model with terms of treatment, pooled investigator, and baseline.

Outcome measures

Outcome measures
Measure	Duloxetine n=221 Participants Participants received 60 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week (Acute Treatment Period) followed by 60-120 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.	Escitalopram n=214 Participants Participants received 10 mg of escitalopram QD po for 1 week (Acute Treatment Period) followed by 10-20 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.
Change From Baseline in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) Total and Item Scores at Week 8 Total Score	-6.96 units on a scale Standard Error 0.34	-6.91 units on a scale Standard Error 0.35
Change From Baseline in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) Total and Item Scores at Week 8 Motivation/Interest/Enthusiasm Score	-1.34 units on a scale Standard Error 0.07	-1.35 units on a scale Standard Error 0.07
Change From Baseline in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) Total and Item Scores at Week 8 Wakefulness/Alertness Score	-0.96 units on a scale Standard Error 0.06	-1.00 units on a scale Standard Error 0.06
Change From Baseline in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) Total and Item Scores at Week 8 Energy Score	-1.28 units on a scale Standard Error 0.07	-1.21 units on a scale Standard Error 0.07
Change From Baseline in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) Total and Item Scores at Week 8 Ability to Focus/Sustain Attention Score	-0.99 units on a scale Standard Error 0.06	-1.02 units on a scale Standard Error 0.06
Change From Baseline in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) Total and Item Scores at Week 8 Ability to Remember/Recall Information Score	-0.91 units on a scale Standard Error 0.06	-0.85 units on a scale Standard Error 0.06
Change From Baseline in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) Total and Item Scores at Week 8 Ability to Find Words Score	-0.69 units on a scale Standard Error 0.05	-0.71 units on a scale Standard Error 0.05
Change From Baseline in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) Total and Item Scores at Week 8 Sharpness/Mental Acuity Score	-0.79 units on a scale Standard Error 0.05	-0.85 units on a scale Standard Error 0.06

SECONDARY outcome

Timeframe: Baseline, 8 weeks

Population: All randomized participants with a baseline and at least 1 post-baseline result.

The SDS is a participant-rated assessment. Total scores range from 0-30 with higher values indicating greater disruption in the participant's work/social/family life. Items 1-3 assess the effect of the participant's symptoms on work/school schedule, social life/leisure activities, and family life/home responsibilities, respectively. Item scores are 0-10; higher values indicate greater disruption. Number of unproductive days and days lost in past week (symptom related) were reported. LS Mean Value was calculated from an ANCOVA model with terms of treatment, pooled investigator, and baseline.

Outcome measures

Outcome measures
Measure	Duloxetine n=211 Participants Participants received 60 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week (Acute Treatment Period) followed by 60-120 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.	Escitalopram n=209 Participants Participants received 10 mg of escitalopram QD po for 1 week (Acute Treatment Period) followed by 10-20 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.
Change From Baseline in the Sheehan Disability Scale (SDS) Total and Individual Scores at Week 8 SDS Total Score	-7.55 units on a scale Standard Error 0.40	-7.67 units on a scale Standard Error 0.41
Change From Baseline in the Sheehan Disability Scale (SDS) Total and Individual Scores at Week 8 SDS Work Score	-2.42 units on a scale Standard Error 0.14	-2.29 units on a scale Standard Error 0.14
Change From Baseline in the Sheehan Disability Scale (SDS) Total and Individual Scores at Week 8 SDS Family Score (N=212, 210)	-2.51 units on a scale Standard Error 0.16	-2.67 units on a scale Standard Error 0.16
Change From Baseline in the Sheehan Disability Scale (SDS) Total and Individual Scores at Week 8 SDS Social Score (N=212, 210)	-2.56 units on a scale Standard Error 0.16	-2.72 units on a scale Standard Error 0.16
Change From Baseline in the Sheehan Disability Scale (SDS) Total and Individual Scores at Week 8 SDS Days Lost Score (N=208, 204)	-0.55 units on a scale Standard Error 0.11	-0.60 units on a scale Standard Error 0.11
Change From Baseline in the Sheehan Disability Scale (SDS) Total and Individual Scores at Week 8 SDS Days Unproductive Score (N=209, 205)	-1.78 units on a scale Standard Error 0.13	-1.89 units on a scale Standard Error 0.13

SECONDARY outcome

Timeframe: Baseline through 8 weeks

Population: All randomized participants with a baseline and at least 1 post-baseline result.

Relapse is defined as achieving a Montgomery-Asberg Depression Rating Scale (MADRS) total score≥16 at any time after baseline. The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms).

Outcome measures

Outcome measures
Measure	Duloxetine n=243 Participants Participants received 60 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week (Acute Treatment Period) followed by 60-120 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.	Escitalopram n=237 Participants Participants received 10 mg of escitalopram QD po for 1 week (Acute Treatment Period) followed by 10-20 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.
Percentage of Participants Who Relapsed During 8 Weeks	11.9 percentage of participants	11.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline through 8 weeks

Population: Number of participants in each treatment group having time to relapse plus the participants censored. Duloxetine had 200 participants censored and escitalopram had 199 participants censored.

The number of days from baseline to the first relapse is defined as reaching a MADRS Total Score≥16. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). Censored participants were included in the Kaplan-Meier analysis, the minimum and maximum time to relapse have been calculated and reported here. Median time to relapse and quartiles could not be computationally calculated using the Kaplan-Meier procedure due to low event rate and high completion rate (censored).

Outcome measures

Outcome measures
Measure	Duloxetine n=229 Participants Participants received 60 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week (Acute Treatment Period) followed by 60-120 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.	Escitalopram n=225 Participants Participants received 10 mg of escitalopram QD po for 1 week (Acute Treatment Period) followed by 10-20 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.
Number of Days From Baseline to Relapse as Defined by Montgomery-Asberg Depression Rating Scale (MADRS) Total Score ≥16 During 8 Weeks Minimum Number of Days from Baseline	4.00 days	4.00 days
Number of Days From Baseline to Relapse as Defined by Montgomery-Asberg Depression Rating Scale (MADRS) Total Score ≥16 During 8 Weeks Maximum Number of Days from Baseline	81.00 days	68.00 days

SECONDARY outcome

Timeframe: Baseline through 8 weeks

Population: All randomized participants.

Percentage of participants who discontinue after baseline due to lack of efficacy in the investigator's opinion.

Outcome measures

Outcome measures
Measure	Duloxetine n=244 Participants Participants received 60 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week (Acute Treatment Period) followed by 60-120 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.	Escitalopram n=239 Participants Participants received 10 mg of escitalopram QD po for 1 week (Acute Treatment Period) followed by 10-20 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.
Percentage of Participants Who Discontinue Due to Lack of Efficacy During 8 Weeks	2.0 percentage of participants	1.3 percentage of participants

Adverse Events

Duloxetine

Serious events: 3 serious events

Other events: 130 other events

Deaths: 0 deaths

Escitalopram

Serious events: 3 serious events

Other events: 100 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Duloxetine n=244 participants at risk Participants received 60 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week (Acute Treatment Period) followed by 60-120 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.	Escitalopram n=239 participants at risk Participants received 10 mg of escitalopram QD po for 1 week (Acute Treatment Period) followed by 10-20 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.
Gastrointestinal disorders Melaena	0.00% 0/244	0.42% 1/239 • Number of events 1
Hepatobiliary disorders Cholelithiasis	0.41% 1/244 • Number of events 1	0.00% 0/239
Nervous system disorders Syncope	0.00% 0/244	0.42% 1/239 • Number of events 1
Psychiatric disorders Depression	0.41% 1/244 • Number of events 1	0.00% 0/239
Psychiatric disorders Insomnia	0.00% 0/244	0.42% 1/239 • Number of events 1
Psychiatric disorders Suicide attempt	0.00% 0/244	0.42% 1/239 • Number of events 1
Respiratory, thoracic and mediastinal disorders Asthma	0.41% 1/244 • Number of events 1	0.00% 0/239

Other adverse events

Other adverse events
Measure	Duloxetine n=244 participants at risk Participants received 60 milligrams (mg) of duloxetine once daily (QD) by mouth (po) for 1 week (Acute Treatment Period) followed by 60-120 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.	Escitalopram n=239 participants at risk Participants received 10 mg of escitalopram QD po for 1 week (Acute Treatment Period) followed by 10-20 mg QD po for the remaining 7 weeks (Optimization Period), with an option to continue treatment for an additional 2 weeks.
Gastrointestinal disorders Constipation	9.4% 23/244 • Number of events 23	3.8% 9/239 • Number of events 9
Gastrointestinal disorders Dry mouth	5.3% 13/244 • Number of events 14	3.3% 8/239 • Number of events 8
Gastrointestinal disorders Nausea	10.7% 26/244 • Number of events 26	11.7% 28/239 • Number of events 28
Metabolism and nutrition disorders Decreased appetite	3.3% 8/244 • Number of events 8	1.3% 3/239 • Number of events 3
Nervous system disorders Dizziness	2.9% 7/244 • Number of events 8	6.3% 15/239 • Number of events 15
Nervous system disorders Headache	6.6% 16/244 • Number of events 16	8.4% 20/239 • Number of events 20
Nervous system disorders Somnolence	5.7% 14/244 • Number of events 15	3.3% 8/239 • Number of events 9
Psychiatric disorders Anxiety	3.7% 9/244 • Number of events 9	0.42% 1/239 • Number of events 1
Psychiatric disorders Insomnia	7.0% 17/244 • Number of events 21	4.2% 10/239 • Number of events 10
Skin and subcutaneous tissue disorders Hyperhidrosis	3.3% 8/244 • Number of events 8	0.84% 2/239 • Number of events 2

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60