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Early Versus Delayed Switch in Medication in Patients With Major Depressive Disorder

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ClinicalTrials.gov Identifier: NCT00810069
Recruitment Status : Completed
First Posted : December 17, 2008
Results First Posted : June 21, 2011
Last Update Posted : June 21, 2011
Sponsor:
Information provided by:
Eli Lilly and Company

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Major Depressive Disorder
Interventions Drug: Duloxetine Hydrochloride
Drug: Escitalopram
Enrollment 840
Recruitment Details Participants showing improvement (≥30% baseline score reduction on the HAMD-17) during Period I did not continue to Period II of the study. Qualified participants for Period II were randomized to either Early Intervention Strategy Arm or Delayed Intervention Strategy Arm.
Pre-assignment Details Baseline demographics and primary and secondary outcomes are reported only for Period II (Double Blind Treatment Strategy). Adverse events (AEs) are reported for Period I (Acute Escitalopram Treatment) and Period II.
Arm/Group Title Escitalopram (Acute Treatment) Early Intervention Delayed Intervention
Hide Arm/Group Description Escitalopram 10 milligrams (mg) per day for 4 weeks Duloxetine flexible dose (60 or 120 milligrams [mg] daily) for 12 weeks Escitalopram flexible dose (10 to 20 milligrams [mg] daily) for 4 weeks. Then in participants with no-response, switch treatment to duloxetine flexible dose (60 or 120 mg daily) for 8 weeks. In participants with a response continue treatment with escitalopram (10 to 20 milligrams [mg] daily) for 8 weeks.
Period Title: Lead-in Period I
Started 840 0 0
Completed 566 0 0
Not Completed 274 0 0
Reason Not Completed
Adverse Event             43             0             0
Lack of Efficacy             1             0             0
Lost to Follow-up             19             0             0
Physician Decision             1             0             0
Protocol Violation             1             0             0
Withdrawal by Subject             46             0             0
Protocol entry criterion not met             5             0             0
Randomization criteria not met             158             0             0
Period Title: Double-Blind Period II
Started 0 282 284 [1]
Completed 0 226 212
Not Completed 0 56 72
Reason Not Completed
Adverse Event             0             9             8
Lack of Efficacy             0             7             12
Lost to Follow-up             0             9             9
Physician Decision             0             0             1
Withdrawal by Subject             0             21             35
Protocol entry criterion not met             0             0             1
Clinical relapse             0             3             0
Protocol Violation             0             7             6
[1]
At Week 8 - delayed intervention divided by response to treatment (nonresponders or responders).
Arm/Group Title Early Intervention Delayed Intervention Total
Hide Arm/Group Description Duloxetine flexible dose (60 or 120 milligrams [mg] daily) for 12 weeks Escitalopram flexible dose (10 to 20 milligrams [mg] daily) for 4 weeks. Then in participants with no-response, switch treatment to duloxetine flexible dose (60 or 120 mg daily) for 8 weeks. In participants with a response continue treatment with escitalopram (10 to 20 milligrams [mg] daily) for 8 weeks. Total of all reporting groups
Overall Number of Baseline Participants 282 284 566
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 282 participants 284 participants 566 participants
48.3  (13.48) 47.4  (12.72) 47.9  (13.10)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 282 participants 284 participants 566 participants
Female
196
  69.5%
197
  69.4%
393
  69.4%
Male
86
  30.5%
87
  30.6%
173
  30.6%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 282 participants 284 participants 566 participants
France 54 54 108
Hungary 6 6 12
Slovenia 6 4 10
Greece 10 10 20
Spain 71 73 144
Turkey 10 10 20
Romania 18 18 36
Denmark 12 14 26
Netherlands 5 4 9
Italy 19 20 39
Sweden 71 71 142
Race  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 282 participants 284 participants 566 participants
Black or African American 2 2 4
White 280 282 562
Clinical Global Impression-Major Depressive Disorder-Severity (CGI-MDD-S) Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 282 participants 284 participants 566 participants
4.6  (0.59) 4.6  (0.64) 4.6  (0.62)
[1]
Measure Description: 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 participants.
Quick Inventory of Depressive Symptomatology-Self Reported (QIDS16SR) Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 282 participants 284 participants 566 participants
16.4  (3.82) 16.7  (3.43) 16.5  (3.63)
[1]
Measure Description: A 16-item participant-rated measure of depressive symptomatology. The total score ranges from 0 to 27 with higher scores indicative of greater severity.
17-item Hamilton Depression Rating Scale (HAMD-17) Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 282 participants 284 participants 566 participants
24.0  (3.57) 24.4  (3.83) 24.2  (3.70)
[1]
Measure Description: The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe).
Visual Analog Scale (VAS) Overall Pain Severity   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 282 participants 284 participants 566 participants
3.6  (2.76) 3.8  (2.81) 3.7  (2.78)
[1]
Measure Description: VAS for pain consists of 6 questions that assess overall pain, headache, back pain, shoulder pain, pain interference with daily activities, and pain while awake. Participant rates pain on a 10 centimeter (cm) line between two anchors (0= no pain and 10=very severe pain).
Sheehan Disability Scale (SDS) Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 282 participants 284 participants 566 participants
19.9  (5.12) 19.9  (5.52) 19.9  (5.32)
[1]
Measure Description: The SDS is completed by the participant and is used to assess the effect of the participant's symptoms on their work/social/family life. Total scores range from 0 to 30 with higher values indicating greater disruption in the participant's work/social/family life.
Euro Quality of Life-5 Dimensions Questionnaire (EQ-5D) Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 282 participants 284 participants 566 participants
EQ-5D UK Population-based Index Score 0.40  (0.291) 0.34  (0.312) 0.37  (0.303)
Health State Score 4.23  (1.873) 3.86  (1.704) 4.05  (1.798)
[1]
Measure Description: EQ-5D: a generic, multidimensional, health-related, quality of life instrument. Participants rate health state in 5 domains: mobility, self-care, usual activities, pain/discomfort, mood. A single score between 1-3 is generated for each domain. Outcome rating on 5 domains is mapped to a single index through an algorithm. Index ranges between 0-1 with higher score indicating better health state perceived by participant. Health State Score: self-rated health on a vertical visual analogue scale measured in centimeters. Best imaginable health state=10 and worst imaginable health state=0.
Number of work hours worked per week  
Mean (Standard Deviation)
Unit of measure:  Hours
Number Analyzed 282 participants 284 participants 566 participants
38.0  (8.30) 37.2  (9.53) 37.6  (8.94)
Number of work hours missed in the last 4 weeks   [1] 
Mean (Standard Deviation)
Unit of measure:  Hours
Number Analyzed 282 participants 284 participants 566 participants
86.9  (63.09) 87.5  (66.32) 87.2  (64.67)
[1]
Measure Description: Only those participants who missed at least 1 hour of work were included: 79 participants in the Early Intervention Strategy group and 93 participants in the Delayed Intervention Strategy group.
Number of work hours missed due to depression in the last 4 weeks   [1] 
Mean (Standard Deviation)
Unit of measure:  Hours
Number Analyzed 282 participants 284 participants 566 participants
88.8  (64.14) 88.5  (67.05) 88.6  (65.56)
[1]
Measure Description: Only those participants who missed at least 1 hour of work due to depression were included: 73 participants in the Early Intervention Strategy group and 90 participants in the Delayed Intervention Strategy group.
Number of visits to primary healthcare provider due to depression in the last 4 weeks  
Mean (Standard Deviation)
Unit of measure:  Visits
Number Analyzed 282 participants 284 participants 566 participants
1.6  (0.95) 1.8  (1.10) 1.7  (1.03)
Number of visits to emergency room or equivalent facility due to depression in the last 4 weeks  
Mean (Standard Deviation)
Unit of measure:  Visits
Number Analyzed 282 participants 284 participants 566 participants
1.1  (0.27) 1.1  (0.48) 1.1  (0.40)
Number of visits to other specialists due to depression in the last 4 weeks  
Mean (Standard Deviation)
Unit of measure:  Visits
Number Analyzed 282 participants 284 participants 566 participants
2.0  (1.44) 1.6  (0.98) 1.8  (1.26)
Has the participant been hospitalized due to depression in the last 4 weeks  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 282 participants 284 participants 566 participants
Yes 4 5 9
No 277 278 555
Unknown 1 0 1
Missing 0 1 1
1.Primary Outcome
Title Time to Confirmed Response by ≥ 50% Change From Baseline Reduction in the Hamilton Depression Rating Scale-17 Items (HAMD-17)
Hide Description Time to confirmed response is defined as the time from the day of study randomization (Visit 2) to the date of first observation of confirmed response defined as ≥ 50% baseline score reduction on the HAMD-17 for 2 consecutive visits. The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale, e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe).
Time Frame Week 4 through Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Early Intervention Delayed Intervention
Hide Arm/Group Description:
Duloxetine flexible dose (60 or 120 milligrams [mg] daily) for 12 weeks
Escitalopram flexible dose (10 to 20 milligrams [mg] daily) for 4 weeks. Then in participants with no-response, switch treatment to duloxetine flexible dose (60 or 120 mg daily) for 8 weeks. In participants with a response continue treatment with escitalopram (10 to 20 milligrams [mg] daily) for 8 weeks.
Overall Number of Participants Analyzed 282 284
Median (95% Confidence Interval)
Unit of Measure: weeks
6.4
(6.0 to 8.0)
8.0
(6.4 to 8.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Early Intervention, Delayed Intervention
Comments Kaplan-Meier Estimates (weeks): analysis of early intervention versus delayed intervention strategies
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.213
Comments P-value is for early intervention strategy versus delayed intervention strategy.
Method Kaplan-Meier Analysis
Comments Kaplan-Meier analysis with Wilcoxon test to compare strategies.
2.Primary Outcome
Title Estimated Probability of Not Reaching Confirmed Response at 12 Weeks Based on the Survival Function for the Time to Confirmed Response
Hide Description Survival function is estimating the probability of participants not achieving confirmed response after 12 weeks. Confirmed response is defined as >=50% change from baseline reduction in the Hamilton Depression Rating Scale-17 Items (HAMD-17). The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe).
Time Frame Week 4 through Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Population
Arm/Group Title Early Intervention Delayed Intervention
Hide Arm/Group Description:
Duloxetine flexible dose (60 or 120 milligrams [mg] daily) for 12 weeks
Escitalopram flexible dose (10 to 20 milligrams [mg] daily) for 4 weeks. Then in participants with no-response, switch treatment to duloxetine flexible dose (60 or 120 mg daily) for 8 weeks. In participants with a response continue treatment with escitalopram (10 to 20 milligrams [mg] daily) for 8 weeks.
Overall Number of Participants Analyzed 282 284
Mean (95% Confidence Interval)
Unit of Measure: estimated probability (percent)
28
(22 to 34)
26
(20 to 32)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Early Intervention, Delayed Intervention
Comments Survival function estimated over a 12 week period (Week 4 through Week 16): analysis of early intervention versus delayed intervention strategies
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.653
Comments P-value is for comparison of early intervention versus delayed intervention as a function of survival rate over a 12 week period (Week 4 through Week 16).
Method Kaplan Meier analysis
Comments P-value for comparison of rates is based on normal approximation using Greenwood's estimation for standard error.
Method of Estimation Estimation Parameter survival rate difference
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
-0.06 to 0.10
Estimation Comments [Not Specified]
3.Primary Outcome
Title Time to Confirmed Remission by a Hamilton Depression Rating Scale-17 Items (HAMD-17) Score of ≤ 7 That is Maintained for Two Consecutive Visits
Hide Description Time to confirmed remission is defined as the time from the day of study randomization (Visit 2) to the date of first observation of confirmed remission defined as a score on the HAMD-17 of ≤ 7 for 2 consecutive visits. The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe).
Time Frame Week 4 through Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Population
Arm/Group Title Early Intervention Delayed Intervention
Hide Arm/Group Description:
Duloxetine flexible dose (60 or 120 milligrams [mg] daily) for 12 weeks
Escitalopram flexible dose (10 to 20 milligrams [mg] daily) for 4 weeks. Then in participants with no-response, switch treatment to duloxetine flexible dose (60 or 120 mg daily) for 8 weeks. In participants with a response continue treatment with escitalopram (10 to 20 milligrams [mg] daily) for 8 weeks.
Overall Number of Participants Analyzed 282 284
Median (95% Confidence Interval)
Unit of Measure: weeks
12.9 [1] 
(11.0 to NA)
NA [2] 
(12.3 to NA)
[1]
No maximum value was reported for the 95% confidence interval. It was not reported as it could not be estimated due to the low number of events.
[2]
50% remission (median) could not be estimated for delayed intervention arm due to the low number of events.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Early Intervention, Delayed Intervention
Comments Kaplan-Meier estimates (weeks): analysis of early intervention versus delayed intervention strategies
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.075
Comments P-value is for early intervention strategy versus delayed intervention strategy.
Method Kaplan-Meier analysis
Comments Kaplan-Meier analysis with Wilcoxon test to compare strategies
4.Primary Outcome
Title Estimated Probability of Not Reaching Confirmed Remission at 12 Weeks Based on the Survival Function for the Time to Confirmed Remission
Hide Description Survival function is estimating the probability of participants not achieving confirmed remission. Confirmed remission is defined as a Hamilton Depression Rating Scale-17 Items (HAMD-17) Score of ≤ 7 that is maintained for two consecutive visits. The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe).
Time Frame Week 4 through Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Population
Arm/Group Title Early Intervention Delayed Intervention
Hide Arm/Group Description:
Duloxetine flexible dose (60 or 120 milligrams [mg] daily) for 12 weeks
Escitalopram flexible dose (10 to 20 milligrams [mg] daily) for 4 weeks. Then in participants with no-response, switch treatment to duloxetine flexible dose (60 or 120 mg daily) for 8 weeks. In participants with a response continue treatment with escitalopram (10 to 20 milligrams [mg] daily) for 8 weeks.
Overall Number of Participants Analyzed 282 284
Mean (95% Confidence Interval)
Unit of Measure: estimated probability (percent)
52
(46 to 58)
59
(53 to 66)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Early Intervention, Delayed Intervention
Comments Survival function estimated over a 12 week period (Week 4 through Week 16): analysis of early intervention versus delayed intervention strategies
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.116
Comments P-value is for comparison of early intervention versus delayed intervention as a function of survival rate over a 12 week period (Week 4 through Week 16).
Method Kaplan-Meier analysis
Comments P-value for comparison of rates is based on normal approximation using Greenwood's estimation for standard error.
Method of Estimation Estimation Parameter Survival rate difference
Estimated Value -0.07
Confidence Interval (2-Sided) 95%
-0.16 to 0.02
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Time to Confirmed Response as Defined by ≥ 50% Reduction From Baseline Reduction in the 16-Item Quick Inventory of Depressive Symptomatology Self Report (QIDS16SR) That is Reported for Two Consecutive Visits
Hide Description Time to confirmed response is defined as the time from the day of study randomization (Visit 2) to the date of first observation of confirmed response. QIDS16SR is a 16-item participant-rated measure of depressive symptomatology. The total score ranges from 0 to 27 with higher scores indicative of greater severity.
Time Frame Week 4 through Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Population
Arm/Group Title Early Intervention Delayed Intervention
Hide Arm/Group Description:
Duloxetine flexible dose (60 or 120 milligrams [mg] daily) for 12 weeks
Escitalopram flexible dose (10 to 20 milligrams [mg] daily) for 4 weeks. Then in participants with no-response, switch treatment to duloxetine flexible dose (60 or 120 mg daily) for 8 weeks. In participants with a response continue treatment with escitalopram (10 to 20 milligrams [mg] daily) for 8 weeks.
Overall Number of Participants Analyzed 282 284
Median (95% Confidence Interval)
Unit of Measure: weeks
6.0
(5.0 to 8.0)
6.9
(5.3 to 8.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Early Intervention, Delayed Intervention
Comments Analysis of early intervention strategy versus delayed intervention strategy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.947
Comments P-value is for early intervention strategy versus delayed intervention strategy.
Method Kaplan Meier analysis
Comments Kaplan-Meier analysis with Wilcoxon test to compare strategies.
6.Secondary Outcome
Title Time to Confirmed Remission as Defined by a 16-Item Quick Inventory of Depressive Symptomatology Self Report (QIDS16SR) Score of ≤ 5 That is Maintained for Two Consecutive Visits.
Hide Description Time to confirmed remission is defined as the time from the day of study randomization (Visit 2) to the date of first observation of confirmed remission. A 16-item participant-rated measure of depressive symptomatology. The total score ranges from 0 to 27 with higher scores indicative of greater severity.
Time Frame Week 4 through Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Population
Arm/Group Title Early Intervention Delayed Intervention
Hide Arm/Group Description:
Duloxetine flexible dose (60 or 120 milligrams [mg] daily) for 12 weeks
Escitalopram flexible dose (10 to 20 milligrams [mg] daily) for 4 weeks. Then in participants with no-response, switch treatment to duloxetine flexible dose (60 or 120 mg daily) for 8 weeks. In participants with a response continue treatment with escitalopram (10 to 20 milligrams [mg] daily) for 8 weeks.
Overall Number of Participants Analyzed 280 284
Median (95% Confidence Interval)
Unit of Measure: weeks
NA [1] 
(12.3 to NA)
NA [1] 
(12.3 to NA)
[1]
It could not be estimated due to the low number of events.
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Early Intervention, Delayed Intervention
Comments Analysis of early intervention strategy versus delayed intervention strategy
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.597
Comments P-value is for early intervention versus delayed intervention strategies.
Method Kaplan-Meier analysis
Comments Kaplan-Meier analysis with Wilcoxon test to compare strategies
7.Secondary Outcome
Title Clinical Global Impressions of Severity (CGI-S) Scale
Hide Description 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 participants).
Time Frame Baseline, Week 4, Week 6, Week 8, Week 10, Week 12, Week 14, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Population
Arm/Group Title Early Intervention Delayed Intervention
Hide Arm/Group Description:
Duloxetine flexible dose (60 or 120 milligrams [mg] daily) for 12 weeks
Escitalopram flexible dose (10 to 20 milligrams [mg] daily) for 4 weeks. Then in participants with no-response, switch treatment to duloxetine flexible dose (60 or 120 mg daily) for 8 weeks. In participants with a response continue treatment with escitalopram (10 to 20 milligrams [mg] daily) for 8 weeks.
Overall Number of Participants Analyzed 282 284
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (n=282, 284) 4.6  (0.59) 4.6  (0.64)
Week 4 (n=281, 284) 4.3  (0.61) 4.3  (0.66)
Week 6 (n=271, 277) 3.6  (0.88) 3.7  (0.97)
Week 8 (n=254, 254) 3.2  (1.11) 3.3  (1.15)
Week 10 (n=231, 236) 2.8  (1.17) 2.9  (1.22)
Week 12 (n=203, 214) 2.6  (1.21) 2.7  (1.20)
Week 14 (n=184, 194) 2.4  (1.13) 2.5  (1.17)
Week 16 (n=178, 182) 2.2  (1.09) 2.2  (1.11)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Early Intervention, Delayed Intervention
Comments Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.624
Comments P-value for Week 6: Analysis of early versus delayed intervention strategies LS Mean/Estimate
Method Mixed Models Analysis
Comments Mixed models repeated measures with fixed effects for strategy, country, visit, strategy-by-visit interaction, baseline score and baseline-by visit
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.22 to 0.13
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.09
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Early Intervention, Delayed Intervention
Comments Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.208
Comments P-value for Week 8: Analysis of early versus delayed intervention strategies LS Mean/Estimate
Method Mixed Models Analysis
Comments Mixed Models repeated measures with fixed effects for strategy, country, visit, strategy-by-visit interaction, baseline score and baseline-by-visit
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.11
Confidence Interval (2-Sided) 95%
-0.29 to 0.06
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.09
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Early Intervention, Delayed Intervention
Comments Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 10
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.044
Comments P-value for Week 10: Analysis of early versus delayed intervention strategies LS Mean/Estimate
Method Mixed Models Analysis
Comments Mixed models repeated measures with fixed effects for strategy, country, visit, strategy-by-visit interaction, baseline score and baseline-by-visit
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.19
Confidence Interval (2-Sided) 95%
-0.37 to -0.00
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.09
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Early Intervention, Delayed Intervention
Comments Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.086
Comments P-value for Week 12: Analysis of early versus delayed intervention strategies LS Mean/Estimate
Method Mixed Models Analysis
Comments Mixed models repeated measures with fixed effects for strategy, country, visit, strategy-by-visit interactions, baseline score and baseline-by-visit
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.16
Confidence Interval (2-Sided) 95%
-0.35 to 0.02
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.10
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Early Intervention, Delayed Intervention
Comments Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 14
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.181
Comments P-value for Week 14: Analysis of early versus delayed intervention strategies LS Mean/Estimate
Method Mixed Models Analysis
Comments Mixed models repeated measures with fixed effects for strategy, country, visit, strategy-by-visit interaction, baseline score and baseline-by-visit
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.13
Confidence Interval (2-Sided) 95%
-0.33 to 0.06
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.10
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Early Intervention, Delayed Intervention
Comments Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 16
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.994
Comments P-value for Week 16: Analysis of early versus delayed intervention strategies LS Mean/Estimate
Method Mixed Models Analysis
Comments Mixed models repeated measures with fixed effects for strategy, country, visit, strategy-by-visit interaction, baseline score and baseline-by-visit
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-0.20 to 0.20
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.10
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Visual Analog Scale (VAS) - Overall Pain Severity
Hide Description VAS for pain consists of 6 questions that assess overall pain, headache, back pain, shoulder pain, pain interference with daily activities, and pain while awake. Participant rates pain on a 10 centimeter (cm) line between two anchors (0= no pain and 10=very severe pain).
Time Frame Baseline, Week 4, Week 6, Week 8, Week 10, Week 12, Week 14, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Population
Arm/Group Title Early Intervention Delayed Intervention
Hide Arm/Group Description:
Duloxetine flexible dose (60 or 120 milligrams [mg] daily) for 12 weeks
Escitalopram flexible dose (10 to 20 milligrams [mg] daily) for 4 weeks. Then in participants with no-response, switch treatment to duloxetine flexible dose (60 or 120 mg daily) for 8 weeks. In participants with a response continue treatment with escitalopram (10 to 20 milligrams [mg] daily) for 8 weeks.
Overall Number of Participants Analyzed 282 284
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (n=282, 284) 3.6  (2.76) 3.8  (2.81)
Week 4 (n=281, 283) 3.0  (2.54) 3.5  (2.77)
Week 6 (n=270, 271) 2.6  (2.41) 3.3  (2.85)
Week 8 (n=245, 241) 2.4  (2.53) 3.0  (2.70)
Week 10 (n=207, 204) 2.4  (2.48) 2.7  (2.60)
Week 12 (n=170, 181) 2.1  (2.42) 2.6  (2.66)
Week 14 (n=151, 152) 2.0  (2.35) 2.5  (2.54)
Week 16 (n=143, 152) 2.0  (2.32) 2.3  (2.55)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Early Intervention, Delayed Intervention
Comments Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 6
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.001
Comments P-value for Week 6: Analysis of early versus delayed intervention strategies LS Mean/Estimate
Method Mixed Models Analysis
Comments Mixed models repeated measures with fixed effects for strategy, country, visit, strategy-by-visit interaction, baseline score and baseline-by visit
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.62
Confidence Interval (2-Sided) 95%
-0.98 to -0.25
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.19
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Early Intervention, Delayed Intervention
Comments Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.010
Comments P-value for Week 8: Analysis of early versus delayed intervention strategies LS Mean/Estimate
Method Mixed Models Analysis
Comments Mixed models repeated measures with fixed effects for strategy, country, visit, strategy-by-visit interaction, baseline score and baseline-by-visit
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.50
Confidence Interval (2-Sided) 95%
-0.87 to -0.12
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.19
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Early Intervention, Delayed Intervention
Comments Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 10
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.445
Comments P-value for Week 10: analysis of early versus delayed intervention strategies LS Mean/Estimate
Method Mixed Models Analysis
Comments Mixed models repeated measures with fixed effects for strategy, country, visit, strategy-by-visit interaction, baseline score and baseline-by-visit
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-0.55 to 0.24
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.20
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Early Intervention, Delayed Intervention
Comments Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.169
Comments P-value for Week 12: Analysis of early versus delayed intervention strategies LS Mean/Estimate
Method Mixed Models Analysis
Comments Mixed models repeated measures with fixed effects for strategy, country, visit, strategy-by-visit interaction, baseline score and baseline-by-visit
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.29
Confidence Interval (2-Sided) 95%
-0.71 to 0.12
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.21
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Early Intervention, Delayed Intervention
Comments Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 14
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.393
Comments P-value for Week 14: Analysis of early versus delayed intervention strategies LS Mean/Estimate
Method Mixed Models Analysis
Comments Mixed models repeated measures with fixed effects for strategy, country, visit, strategy-by-visit interaction, baseline score and baseline-by-visit
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.19
Confidence Interval (2-Sided) 95%
-0.63 to 0.25
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.23
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Early Intervention, Delayed Intervention
Comments Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 16
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.510
Comments P-value for Week 16: Analysis of early versus delayed intervention strategies LS Mean/Estimate
Method Mixed Models Analysis
Comments Mixed models repeated measures with fixed effects for strategy, country, visit, strategy-by-visit interaction, baseline scores and baseline-by-visit
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.15
Confidence Interval (2-Sided) 95%
-0.61 to 0.30
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.23
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Euro Quality of Life Questionnaire-5 Dimensions (EQ-5D) Scale - Health State Score
Hide Description The EQ-5D Health State Score is self-rated health on a vertical, visual analogue scale measured in centimeters (cm) and reported as units on a scale. Best imaginable health state = 10 cm and worst imaginable health state = 0 cm.
Time Frame Baseline, Week 4, Week 8, Week 12, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Population
Arm/Group Title Early Intervention Delayed Intervention
Hide Arm/Group Description:
Duloxetine flexible dose (60 or 120 milligrams [mg] daily) for 12 weeks
Escitalopram flexible dose (10 to 20 milligrams [mg] daily) for 4 weeks. Then in participants with no-response, switch treatment to duloxetine flexible dose (60 or 120 mg daily) for 8 weeks. In participants with a response continue treatment with escitalopram (10 to 20 milligrams [mg] daily) for 8 weeks.
Overall Number of Participants Analyzed 282 283
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (n=281, 283) 4.2  (1.87) 3.9  (1.70)
Week 4 (n=282, 280) 4.9  (1.76) 4.5  (1.62)
Week 8 (n=244, 237) 5.7  (1.88) 5.4  (1.94)
Week 12 (n=169, 177) 5.9  (1.96) 5.8  (1.98)
Week 16 (n=142, 153) 6.5  (1.90) 6.5  (1.94)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Early Intervention, Delayed Intervention
Comments Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.401
Comments P-value for Week 8: Analysis of early intervention versus delayed intervention strategies LS Mean/Estimate
Method Mixed Models Analysis
Comments Mixed models repeated measures with fixed effects for strategy, country, visit, strategy-by-visit interaction, baseline score and baseline-by-visit
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.14
Confidence Interval (2-Sided) 95%
-0.19 to 0.47
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.17
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Early Intervention, Delayed Intervention
Comments Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.618
Comments P-value for Week 12: Analysis of early intervention versus delayed intervention strategies LS Mean/Estimate
Method Mixed Models Analysis
Comments Mixed models repeated measures with fixed effects for strategy, country, visit, strategy-by-visit interaction, baseline score and baseline-by-visit
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.09
Confidence Interval (2-Sided) 95%
-0.27 to 0.46
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.19
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Early Intervention, Delayed Intervention
Comments Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 16
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.856
Comments P-value for Week 16: Analysis of early intervention versus delayed intervention strategies LS Mean/Estimate
Method Mixed Models Analysis
Comments Mixed models repeated measures with fixed effects for strategy, country, visit, strategy-by-visit interaction, baseline score and baseline-by-visit
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.43 to 0.36
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.20
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Euro Quality of Life Questionnaire-5 Dimensions (EQ-5D) Scale - United Kingdom (UK) Population Based Index Score
Hide Description The EQ-5D is a generic, multidimensional, health-related, quality of life instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood. A single score between 1 and 3 is generated for each domain. For each participant, the outcome rating on the 5 domains will be mapped to a single index through an algorithm. The index ranges between 0 and 1, with the higher score indicating a better health state perceived by the participant.
Time Frame Baseline, Week 4, Week 8, Week 12, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Population
Arm/Group Title Early Intervention Delayed Intervention
Hide Arm/Group Description:
Duloxetine flexible dose (60 or 120 milligrams [mg] daily) for 12 weeks
Escitalopram flexible dose (10 to 20 milligrams [mg] daily) for 4 weeks. Then in participants with no-response, switch treatment to duloxetine flexible dose (60 or 120 mg daily) for 8 weeks. In participants with a response continue treatment with escitalopram (10 to 20 milligrams [mg] daily) for 8 weeks.
Overall Number of Participants Analyzed 279 282
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (n=279, 282) 0.4  (0.29) 0.3  (0.31)
Week 4 (n=279, 282) 0.5  (0.30) 0.5  (0.32)
Week 8 (n=244, 238) 0.7  (0.25) 0.6  (0.30)
Week 12 (n=168, 178) 0.7  (0.22) 0.6  (0.28)
Week 16 (n=143, 153) 0.7  (0.24) 0.7  (0.24)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Early Intervention, Delayed Intervention
Comments Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.021
Comments P-value for Week 8: Analysis of early versus delayed intervention LS Mean/Estimate
Method Mixed Models Analysis
Comments Mixed models repeated measures with fixed effects for strategy, country, visit, strategy-by-visit interaction, baseline score and baseline-by-visit
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.05
Confidence Interval (2-Sided) 95%
-0.10 to -0.01
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.02
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Early Intervention, Delayed Intervention
Comments Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.071
Comments P-value for Week 12: Analysis of early versus delayed intervention strategies LS Mean/Estimate
Method Mixed Models Analysis
Comments Mixed models repeated measures with fixed effects for strategy, country, visit, strategy-by-visit interaction, baseline score and baseline-by-visit
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.09 to 0.00
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.02
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Early Intervention, Delayed Intervention
Comments Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 16
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.792
Comments P-value for Week 16: Analysis of early versus delayed intervention strategies LS Mean/Estimate
Method Mixed Models Analysis
Comments Mixed models repeated measures with fixed effects for strategy, country, visit, strategy-by-visit interaction, baseline score and baseline-by-visit
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
-0.05 to 0.06
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.03
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Sheehan Disability Scale (SDS) Normal Functioning Total Score
Hide Description The SDS is completed by the participant and is used to assess the effect of the participant's symptoms on their work/social/family life. Total scores range from 0 to 30 with higher values indicating greater disruption in the participant's work/social/family life.
Time Frame Baseline, Week 4, Week 8, Week 12, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Population
Arm/Group Title Early Intervention Delayed Intervention
Hide Arm/Group Description:
Duloxetine flexible dose (60 or 120 milligrams [mg] daily) for 12 weeks
Escitalopram flexible dose (10 to 20 milligrams [mg] daily) for 4 weeks. Then in participants with no-response, switch treatment to duloxetine flexible dose (60 or 120 mg daily) for 8 weeks. In participants with a response continue treatment with escitalopram (10 to 20 milligrams [mg] daily) for 8 weeks.
Overall Number of Participants Analyzed 216 217
Mean (Standard Deviation)
Unit of Measure: units on a scale
Baseline (n=216, 217) 19.9  (5.12) 19.9  (5.52)
Week 4 (n=215, 215) 16.9  (6.36) 17.5  (6.11)
Week 8 (n=186, 188) 13.5  (6.50) 14.0  (6.79)
Week 12 (n=140, 144) 12.1  (6.84) 13.2  (7.51)
Week 16 (n=113, 121) 10.3  (7.27) 10.2  (6.97)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Early Intervention, Delayed Intervention
Comments Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 8
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.597
Comments P-value for Week 8: Analysis of early versus delayed intervention strategies LS Mean/Estimate
Method Mixed Models Analysis
Comments Mixed models repeated measures with fixed effects for strategy, country, visit, strategy-by-visit interaction, baseline score and baseline-by-visit
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.37
Confidence Interval (2-Sided) 95%
-1.74 to 1.00
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.70
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Early Intervention, Delayed Intervention
Comments Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 12
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.360
Comments P-value for Week 12: Analysis for early versus delayed intervention strategies LS Mean/Estimate
Method Mixed Models Analysis
Comments Mixed models repeated measures with fixed effects for strategy, country, visit, strategy-by-visit interaction, baseline score and baseline-by-visit
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.68
Confidence Interval (2-Sided) 95%
-2.13 to 0.78
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.74
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Early Intervention, Delayed Intervention
Comments Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 16
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.937
Comments P-value for Week 16: Analysis for early versus delayed intervention strategies LS Mean/Estimate
Method Mixed Models Analysis
Comments Mixed models repeated measures with fixed effects for strategy, country, visit, strategy-by-visit interaction, baseline score and baseline-by-visit
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.06
Confidence Interval (2-Sided) 95%
-1.52 to 1.65
Parameter Dispersion
Type: Standard Error of the mean
Value: 0.81
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Resource Utilisation - Number of Hours Worked Per Week
Hide Description [Not Specified]
Time Frame Baseline, Week 4, Week 8, Week 12, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Population, which included all randomized participants with at least 1 post-randomization assessment available after Week 4. For efficacy analyses, participants were included in the analysis if they had a baseline and a post-baseline (after Week 4) value of the variable in question.
Arm/Group Title Early Intervention Delayed Intervention
Hide Arm/Group Description:
Duloxetine flexible dose (60 or 120 milligrams [mg] daily) for 12 weeks
Escitalopram flexible dose (10 to 20 milligrams [mg] daily) for 4 weeks. Then in participants with no-response, switch treatment to duloxetine flexible dose (60 or 120 mg daily) for 8 weeks. In participants with a response continue treatment with escitalopram (10 to 20 milligrams [mg] daily) for 8 weeks.
Overall Number of Participants Analyzed 282 284
Mean (Standard Deviation)
Unit of Measure: Hours
Week 4 (n=153, 159) 37.7  (11.61) 38.6  (13.33)
Week 8 (n=136, 141) 37.9  (9.08) 37.7  (8.42)
Week 12 (n=119, 115) 37.7  (7.40) 38.1  (13.72)
Week 16 (n=96, 96) 37.2  (7.80) 38.0  (14.74)
13.Secondary Outcome
Title Resource Utilisation - Number of Work Hours Missed in the Last 4 Weeks
Hide Description Only those participants who missed at least 1 hour of work were included.
Time Frame Week 4, Week 8, Week 12, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Population, which included all randomized participants with at least 1 post-randomization assessment available after Week 4. For efficacy analyses, participants were included in the analysis if they had a baseline and a post-baseline (after Week 4) value of the variable in question.
Arm/Group Title Early Intervention Delayed Intervention
Hide Arm/Group Description:
Duloxetine flexible dose (60 or 120 milligrams [mg] daily) for 12 weeks
Escitalopram flexible dose (10 to 20 milligrams [mg] daily) for 4 weeks. Then in participants with no-response, switch treatment to duloxetine flexible dose (60 or 120 mg daily) for 8 weeks. In participants with a response continue treatment with escitalopram (10 to 20 milligrams [mg] daily) for 8 weeks.
Overall Number of Participants Analyzed 282 284
Mean (Standard Deviation)
Unit of Measure: Hours
Week 4 (n=73, 89) 88.6  (64.30) 95.0  (67.40)
Week 8 (n=54, 67) 92.5  (66.12) 102.3  (69.38)
Week 12 (n=38, 56) 85.0  (65.73) 104.5  (68.72)
Week 16 (n=25, 39) 91.5  (63.49) 126.4  (63.64)
14.Secondary Outcome
Title Resource Utilisation - Number of Work Hours Missed Due to Depression in the Last 4 Weeks
Hide Description Only those participants who missed at least 1 hour of work due to depression were included.
Time Frame Week 4, Week 8, Week 12, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Population, which included all randomized participants with at least 1 post-randomization assessment available after Week 4. For efficacy analyses, participants were included in the analysis if they had a baseline and a post-baseline (after Week 4) value of the variable in question.
Arm/Group Title Early Intervention Delayed Intervention
Hide Arm/Group Description:
Duloxetine flexible dose (60 or 120 milligrams [mg] daily) for 12 weeks
Escitalopram flexible dose (10 to 20 milligrams [mg] daily) for 4 weeks. Then in participants with no-response, switch treatment to duloxetine flexible dose (60 or 120 mg daily) for 8 weeks. In participants with a response continue treatment with escitalopram (10 to 20 milligrams [mg] daily) for 8 weeks.
Overall Number of Participants Analyzed 282 284
Mean (Standard Deviation)
Unit of Measure: Hours
Week 4 (n=70, 86) 90.6  (64.98) 95.1  (67.90)
Week 8 (n=47, 61) 98.5  (65.34) 109.7  (68.08)
Week 12 (n=31, 52) 98.7  (64.32) 111.4  (66.42)
Week 16 (n=24, 38) 91.9  (64.99) 126.0  (63.40)
15.Secondary Outcome
Title Resource Utilisation - Number of Visits to Primary Healthcare Provider Due to Depression in the Last 4 Weeks
Hide Description [Not Specified]
Time Frame Week 4, Week 8, Week 12, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Population, which included all randomized participants with at least 1 post-randomization assessment available after Week 4. For efficacy analyses, participants were included in the analysis if they had a baseline and a post-baseline (after Week 4) value of the variable in question.
Arm/Group Title Early Intervention Delayed Intervention
Hide Arm/Group Description:
Duloxetine flexible dose (60 or 120 milligrams [mg] daily) for 12 weeks
Escitalopram flexible dose (10 to 20 milligrams [mg] daily) for 4 weeks. Then in participants with no-response, switch treatment to duloxetine flexible dose (60 or 120 mg daily) for 8 weeks. In participants with a response continue treatment with escitalopram (10 to 20 milligrams [mg] daily) for 8 weeks.
Overall Number of Participants Analyzed 282 284
Mean (Standard Deviation)
Unit of Measure: Visits
Week 4 (n=36, 55) 1.5  (1.00) 1.6  (1.04)
Week 8 (n=14, 22) 1.1  (0.27) 1.7  (1.13)
Week 12 (n=8, 12) 1.3  (0.46) 1.6  (1.00)
Week 16 (n=4, 7) 2.0  (2.00) 1.6  (1.13)
16.Secondary Outcome
Title Resource Utilisation - Number of Visits to Other Specialists Due to Depression in the Last 4 Weeks
Hide Description [Not Specified]
Time Frame Week 4, Week 8, Week 12, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Population, which included all randomized participants with at least 1 post-randomization assessment available after Week 4. For efficacy analyses, participants were included in the analysis if they had a baseline and a post-baseline (after Week 4) value of the variable in question.
Arm/Group Title Early Intervention Delayed Intervention
Hide Arm/Group Description:
Duloxetine flexible dose (60 or 120 milligrams [mg] daily) for 12 weeks
Escitalopram flexible dose (10 to 20 milligrams [mg] daily) for 4 weeks. Then in participants with no-response, switch treatment to duloxetine flexible dose (60 or 120 mg daily) for 8 weeks. In participants with a response continue treatment with escitalopram (10 to 20 milligrams [mg] daily) for 8 weeks.
Overall Number of Participants Analyzed 282 284
Mean (Standard Deviation)
Unit of Measure: Visits
Week 4 (n=25, 16) 2.2  (2.05) 1.7  (0.87)
Week 8 (n=8, 8) 1.6  (0.74) 1.9  (1.13)
Week 12 (n=3, 2) 1.7  (1.15) 1.0  (0.00)
Week 16 (n=2, 1) 2.0  (0.00) 3.0 [1]   (NA)
[1]
n=1 participant; therefore SD could not be calculated.
17.Secondary Outcome
Title Resource Utilisation - Has the Participant Been Hospitalized Due to Depression in the Last 4 Weeks - Number of Participants With a Yes Response
Hide Description [Not Specified]
Time Frame Week 4, Week 8, Week 12, Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Population
Arm/Group Title Early Intervention Delayed Intervention
Hide Arm/Group Description:
Duloxetine flexible dose (60 or 120 milligrams [mg] daily) for 12 weeks
Escitalopram flexible dose (10 to 20 milligrams [mg] daily) for 4 weeks. Then in participants with no-response, switch treatment to duloxetine flexible dose (60 or 120 mg daily) for 8 weeks. In participants with a response continue treatment with escitalopram (10 to 20 milligrams [mg] daily) for 8 weeks.
Overall Number of Participants Analyzed 282 284
Measure Type: Number
Unit of Measure: participants
Week 4 1 0
Week 8 0 0
Week 12 0 0
Week 16 0 0
18.Secondary Outcome
Title Number of Participants With Adverse Events (AEs)
Hide Description The list of AEs is located in the Reported Adverse Event module.
Time Frame Baseline through Week 16
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Population
Arm/Group Title Early Intervention Delayed Intervention
Hide Arm/Group Description:
Duloxetine flexible dose (60 or 120 milligrams [mg] daily) for 12 weeks
Escitalopram flexible dose (10 to 20 milligrams [mg] daily) for 4 weeks. Then in participants with no-response, switch treatment to duloxetine flexible dose (60 or 120 mg daily) for 8 weeks. In participants with a response continue treatment with escitalopram (10 to 20 milligrams [mg] daily) for 8 weeks.
Overall Number of Participants Analyzed 282 284
Measure Type: Number
Unit of Measure: participants
Number of participants with adverse events 112 101
Number of participants with serious adverse events 8 4
Time Frame [Not Specified]
Adverse Event Reporting Description Adverse events section reports events for participants in Period I (840) and Period II (282 early intervention, 284 delayed intervention). During Period II (Week 8), delayed intervention participants were subdivided by response to treatment (165 non-responders, 83 responders) and adverse events experienced by these participants are reported here.
 
Arm/Group Title Escitalopram (Acute Treatment) Delayed Intervention (Double Blind) Early Intervention (Double Blind) Delayed Intervention Responders Delayed Intervention Non-Responders
Hide Arm/Group Description Escitalopram 10 mg per day for 4 weeks (one 10 mg-capsule) Escitalopram 10 to 20 mg per day for 4 weeks (one or two 10 mg capsule[s]). Then, non-responders switched to duloxetine 60 or 120 mg per day for 8 weeks, and responders continued on escitalopram 10 to 20 mg per day for 8 weeks. Duloxetine flexible dose (60 or 120 milligram [mg] daily) for 12 weeks. Escitalopram 10 to 20 mg per day for 8 weeks. Duloxetine 60 or 120 mg per day for 8 weeks.
All-Cause Mortality
Escitalopram (Acute Treatment) Delayed Intervention (Double Blind) Early Intervention (Double Blind) Delayed Intervention Responders Delayed Intervention Non-Responders
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Escitalopram (Acute Treatment) Delayed Intervention (Double Blind) Early Intervention (Double Blind) Delayed Intervention Responders Delayed Intervention Non-Responders
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/840 (0.48%)      4/284 (1.41%)      8/282 (2.84%)      1/83 (1.20%)      1/165 (0.61%)    
Cardiac disorders           
Angina pectoris  1  0/840 (0.00%)  0 1/284 (0.35%)  1 0/282 (0.00%)  0 1/83 (1.20%)  1 0/165 (0.00%)  0
Gastrointestinal disorders           
Constipation  1  1/840 (0.12%)  1 0/284 (0.00%)  0 0/282 (0.00%)  0 0/83 (0.00%)  0 0/165 (0.00%)  0
Crohn's disease  1  0/840 (0.00%)  0 0/284 (0.00%)  0 1/282 (0.35%)  1 0/83 (0.00%)  0 0/165 (0.00%)  0
Infections and infestations           
Kidney infection  1  0/840 (0.00%)  0 0/284 (0.00%)  0 1/282 (0.35%)  1 0/83 (0.00%)  0 0/165 (0.00%)  0
Injury, poisoning and procedural complications           
Drug exposure during pregnancy  1  1/840 (0.12%)  1 0/284 (0.00%)  0 0/282 (0.00%)  0 0/83 (0.00%)  0 0/165 (0.00%)  0
Eye injury  1  0/840 (0.00%)  0 0/284 (0.00%)  0 1/282 (0.35%)  1 0/83 (0.00%)  0 0/165 (0.00%)  0
Investigations           
Intraocular pressure increased  1  0/840 (0.00%)  0 0/284 (0.00%)  0 1/282 (0.35%)  1 0/83 (0.00%)  0 0/165 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)           
Breast cancer  1  0/840 (0.00%)  0 1/284 (0.35%)  1 0/282 (0.00%)  0 0/83 (0.00%)  0 1/165 (0.61%)  1
Pancreatic carcinoma  1  0/840 (0.00%)  0 0/284 (0.00%)  0 1/282 (0.35%)  1 0/83 (0.00%)  0 0/165 (0.00%)  0
Nervous system disorders           
Cerebral haemorrhage  1  0/840 (0.00%)  0 0/284 (0.00%)  0 1/282 (0.35%)  1 0/83 (0.00%)  0 0/165 (0.00%)  0
Psychiatric disorders           
Abnormal behaviour  1  0/840 (0.00%)  0 1/284 (0.35%)  1 0/282 (0.00%)  0 0/83 (0.00%)  0 0/165 (0.00%)  0
Confusional state  1  0/840 (0.00%)  0 1/284 (0.35%)  1 0/282 (0.00%)  0 0/83 (0.00%)  0 0/165 (0.00%)  0
Depression  1  1/840 (0.12%)  1 0/284 (0.00%)  0 1/282 (0.35%)  1 0/83 (0.00%)  0 0/165 (0.00%)  0
Insomnia  1  0/840 (0.00%)  0 1/284 (0.35%)  1 0/282 (0.00%)  0 0/83 (0.00%)  0 0/165 (0.00%)  0
Major depression  1  0/840 (0.00%)  0 0/284 (0.00%)  0 1/282 (0.35%)  1 0/83 (0.00%)  0 0/165 (0.00%)  0
Suicidal ideation  1  1/840 (0.12%)  1 0/284 (0.00%)  0 0/282 (0.00%)  0 0/83 (0.00%)  0 0/165 (0.00%)  0
Suicide attempt  1  0/840 (0.00%)  0 0/284 (0.00%)  0 1/282 (0.35%)  1 0/83 (0.00%)  0 0/165 (0.00%)  0
Renal and urinary disorders           
Urinary retention  1  0/840 (0.00%)  0 0/284 (0.00%)  0 1/282 (0.35%)  1 0/83 (0.00%)  0 0/165 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 1%
Escitalopram (Acute Treatment) Delayed Intervention (Double Blind) Early Intervention (Double Blind) Delayed Intervention Responders Delayed Intervention Non-Responders
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   245/840 (29.17%)      99/284 (34.86%)      110/282 (39.01%)      33/83 (39.76%)      60/165 (36.36%)    
Gastrointestinal disorders           
Abdominal pain upper  1  10/840 (1.19%)  10 4/284 (1.41%)  4 1/282 (0.35%)  1 1/83 (1.20%)  1 3/165 (1.82%)  3
Constipation  1  14/840 (1.67%)  14 2/284 (0.70%)  2 7/282 (2.48%)  7 0/83 (0.00%)  0 2/165 (1.21%)  2
Diarrhoea  1  16/840 (1.90%)  16 6/284 (2.11%)  6 7/282 (2.48%)  7 1/83 (1.20%)  1 4/165 (2.42%)  4
Dry mouth  1  26/840 (3.10%)  28 3/284 (1.06%)  3 10/282 (3.55%)  10 2/83 (2.41%)  2 1/165 (0.61%)  1
Dyspepsia  1  0/840 (0.00%)  0 2/284 (0.70%)  2 2/282 (0.71%)  2 1/83 (1.20%)  1 1/165 (0.61%)  1
Flatulence  1  3/840 (0.36%)  3 1/284 (0.35%)  1 0/282 (0.00%)  0 1/83 (1.20%)  1 0/165 (0.00%)  0
Gastric disorder  1  1/840 (0.12%)  1 1/284 (0.35%)  1 0/282 (0.00%)  0 1/83 (1.20%)  1 0/165 (0.00%)  0
Nausea  1  63/840 (7.50%)  63 5/284 (1.76%)  5 14/282 (4.96%)  14 1/83 (1.20%)  1 4/165 (2.42%)  4
Vomiting  1  5/840 (0.60%)  5 2/284 (0.70%)  2 0/282 (0.00%)  0 1/83 (1.20%)  1 1/165 (0.61%)  1
General disorders           
Fatigue  1  7/840 (0.83%)  7 7/284 (2.46%)  7 6/282 (2.13%)  6 4/83 (4.82%)  4 2/165 (1.21%)  2
Malaise  1  2/840 (0.24%)  2 2/284 (0.70%)  2 0/282 (0.00%)  0 0/83 (0.00%)  0 2/165 (1.21%)  2
Immune system disorders           
Seasonal allergy  1  1/840 (0.12%)  1 2/284 (0.70%)  2 1/282 (0.35%)  1 0/83 (0.00%)  0 2/165 (1.21%)  2
Infections and infestations           
Influenza  1  3/840 (0.36%)  3 3/284 (1.06%)  3 5/282 (1.77%)  5 2/83 (2.41%)  2 1/165 (0.61%)  1
Nasopharyngitis  1  10/840 (1.19%)  10 12/284 (4.23%)  13 5/282 (1.77%)  5 3/83 (3.61%)  4 9/165 (5.45%)  9
Investigations           
Biopsy uterus  1  0/840 (0.00%)  0 1/284 (0.35%)  1 0/282 (0.00%)  0 1/83 (1.20%)  1 0/165 (0.00%)  0
Blood pressure diastolic decreased  1  3/840 (0.36%)  3 2/284 (0.70%)  2 5/282 (1.77%)  5 1/83 (1.20%)  1 0/165 (0.00%)  0
Weight decreased  1  4/840 (0.48%)  4 4/284 (1.41%)  4 1/282 (0.35%)  1 2/83 (2.41%)  2 2/165 (1.21%)  2
Weight increased  1  1/840 (0.12%)  1 2/284 (0.70%)  2 0/282 (0.00%)  0 2/83 (2.41%)  2 0/165 (0.00%)  0
Musculoskeletal and connective tissue disorders           
Arthralgia  1  1/840 (0.12%)  1 2/284 (0.70%)  3 1/282 (0.35%)  1 1/83 (1.20%)  2 1/165 (0.61%)  1
Back pain  1  3/840 (0.36%)  4 5/284 (1.76%)  5 2/282 (0.71%)  2 1/83 (1.20%)  1 4/165 (2.42%)  4
Muscle contracture  1  0/840 (0.00%)  0 2/284 (0.70%)  2 0/282 (0.00%)  0 0/83 (0.00%)  0 2/165 (1.21%)  2
Nervous system disorders           
Dizziness  1  15/840 (1.79%)  15 5/284 (1.76%)  5 11/282 (3.90%)  11 3/83 (3.61%)  3 2/165 (1.21%)  2
Headache  1  43/840 (5.12%)  51 24/284 (8.45%)  28 22/282 (7.80%)  43 5/83 (6.02%)  7 17/165 (10.30%)  19
Somnolence  1  6/840 (0.71%)  6 2/284 (0.70%)  2 0/282 (0.00%)  0 0/83 (0.00%)  0 2/165 (1.21%)  2
Tension headache  1  0/840 (0.00%)  0 1/284 (0.35%)  1 0/282 (0.00%)  0 1/83 (1.20%)  1 0/165 (0.00%)  0
Tremor  1  7/840 (0.83%)  7 2/284 (0.70%)  2 3/282 (1.06%)  3 1/83 (1.20%)  1 1/165 (0.61%)  1
Psychiatric disorders           
Anxiety  1  10/840 (1.19%)  10 3/284 (1.06%)  4 2/282 (0.71%)  2 1/83 (1.20%)  1 2/165 (1.21%)  3
Insomnia  1  10/840 (1.19%)  10 4/284 (1.41%)  4 6/282 (2.13%)  9 1/83 (1.20%)  1 3/165 (1.82%)  3
Loss of libido  1  3/840 (0.36%)  3 1/284 (0.35%)  1 0/282 (0.00%)  0 1/83 (1.20%)  1 0/165 (0.00%)  0
Panic attack  1  2/840 (0.24%)  2 2/284 (0.70%)  2 0/282 (0.00%)  0 1/83 (1.20%)  1 1/165 (0.61%)  1
Renal and urinary disorders           
Urinary retention  1  0/840 (0.00%)  0 2/284 (0.70%)  2 0/282 (0.00%)  0 0/83 (0.00%)  0 2/165 (1.21%)  2
Reproductive system and breast disorders           
Ejaculation delayed  1  1/840 (0.12%)  1 1/284 (0.35%)  1 0/282 (0.00%)  0 1/83 (1.20%)  1 0/165 (0.00%)  0
Metrorrhagia  1  1/840 (0.12%)  1 1/284 (0.35%)  1 0/282 (0.00%)  0 1/83 (1.20%)  1 0/165 (0.00%)  0
Vaginal haemorrhage  1  1/840 (0.12%)  1 1/284 (0.35%)  1 0/282 (0.00%)  0 1/83 (1.20%)  1 0/165 (0.00%)  0
Respiratory, thoracic and mediastinal disorders           
Asthma  1  0/840 (0.00%)  0 1/284 (0.35%)  1 0/282 (0.00%)  0 1/83 (1.20%)  1 0/165 (0.00%)  0
Dyspnoea  1  1/840 (0.12%)  1 1/284 (0.35%)  1 0/282 (0.00%)  0 1/83 (1.20%)  1 0/165 (0.00%)  0
Skin and subcutaneous tissue disorders           
Alopecia  1  0/840 (0.00%)  0 1/284 (0.35%)  1 0/282 (0.00%)  0 1/83 (1.20%)  1 0/165 (0.00%)  0
Hyperhidrosis  1  20/840 (2.38%)  20 6/284 (2.11%)  6 12/282 (4.26%)  12 5/83 (6.02%)  5 1/165 (0.61%)  1
Night sweats  1  0/840 (0.00%)  0 2/284 (0.70%)  2 2/282 (0.71%)  2 0/83 (0.00%)  0 2/165 (1.21%)  2
Vascular disorders           
Diastolic hypertension  1  1/840 (0.12%)  1 1/284 (0.35%)  1 0/282 (0.00%)  0 1/83 (1.20%)  1 0/165 (0.00%)  0
Hot flush  1  2/840 (0.24%)  2 0/284 (0.00%)  0 5/282 (1.77%)  5 0/83 (0.00%)  0 0/165 (0.00%)  0
Hypertension  1  19/840 (2.26%)  19 2/284 (0.70%)  2 5/282 (1.77%)  5 0/83 (0.00%)  0 2/165 (1.21%)  2
Hypotension  1  5/840 (0.60%)  5 2/284 (0.70%)  3 1/282 (0.35%)  1 1/83 (1.20%)  2 1/165 (0.61%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 12.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
Phone: 800-545-5979
Layout table for additonal information
Responsible Party: Chief Medical Officer, Eli LIlly
ClinicalTrials.gov Identifier: NCT00810069     History of Changes
Other Study ID Numbers: 12329
F1J-EW-HMGD ( Other Identifier: Eli Lilly and Company )
First Submitted: December 16, 2008
First Posted: December 17, 2008
Results First Submitted: February 4, 2011
Results First Posted: June 21, 2011
Last Update Posted: June 21, 2011