Major Depressive Disorder
Conditions
Keywords
Major Depressive Disorder, Apathy, Duloxetine Hydrochloride, SSRI, Escitalopram
Brief summary
The purpose of this study is to provide a comparison of the apathy, depression, and functional outcomes associated with switching to duloxetine or escitalopram in patients who have previously responded to treatment with a selective serotonin reuptake inhibitor (SSRI) for major depressive disorder and who have residual apathy in the absence of depressed mood.
Detailed description
Apathy is reported by up to 30% of patients with major depressive disorder (MDD) and is hypothesized to be a treatment emergent adverse effect associated with selective serotonin reuptake inhibitor medication. While there is currently no consistent method for treating apathy among psychiatrists, it has been proposed that switching MDD patients to antidepressant medications containing both serotonin and norepinephrine, such as duloxetine, may reduce the incidence and severity of apathy in these patients.
Interventions
DRUGDuloxetine
60-120 milligrams (mg) taken once daily (QD) by mouth (po) for 8 weeks; with option for additional 2 weeks.
DRUGEscitalopram
10-20 mg taken QD po for 8 weeks; with option for additional 2 weeks.
Sponsors
Boehringer Ingelheim
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Have received treatment with an SSRI (escitalopram, sertraline, paroxetine, or citalopram) for major depressive disorder * Females of child-bearing potential to test negative for pregnancy at the time of enrollment based on a urine pregnancy test and agree to use a reliable method of birth control * Apathy Evaluation Scale - Clinician Rated Version (AES-C) total score \>30 at screening and randomization. * Montgomery-Asberg Depression Rating Scale (MADRS) total score ≤15 and Item 1 (apparent sadness) score of \<2 at screening and randomization. * Have a level of understanding sufficient to provide informed consent and to communicate with the investigators, study coordinator, and site personnel.
Exclusion criteria
* Are currently enrolled in, or discontinued within the last 30 days from, a clinical trial involving an off-label use of an investigational drug or device * Have previously completed or withdrawn from this study or any other study investigating duloxetine. * Have had previous lack of response to an adequate trial of duloxetine within the past 12 months or escitalopram at any time. * Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV), diagnosis of mania, bipolar disorder, treatment resistant depression or psychosis; or current suicide risk * Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision(DSM-IV-TR),substance abuse or dependence within the 6 months * Presence of an Axis II disorder * Monoamine oxidase inhibitor (MAOI) treatment within 14 days prior to randomization or the potential need to use an MAOI during the study * Positive urine drug screen for any substance of abuse or excluded medication. * Are pregnant or breast-feeding. * Serious medical illness, requires hospitalization during the study * Have uncontrolled narrow-angle glaucoma. * Have acute liver injury or severe cirrhosis * Abnormal thyroid stimulating hormone (TSH) concentration * Amphetamines, dopaminergic medications or modafinil within 14 days prior to randomization or potential need to use such medications during the study or within 14 days of discontinuation of study drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Apathy Evaluation Scale - Clinician Rated Version (AES-C) Total Score at Week 8 | Baseline, 8 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Rothschild Scale for Antidepressant Tachyphylaxis (RSAT) Total and Individual Item Scores at Week 8 | Baseline, 8 weeks | 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. |
| Patient's Global Impressions of Improvement Scale (PGI-I) Rating Scale Score at Week 8 | 8 weeks | 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. |
| Change From Baseline in the Clinical Global Impression of Severity (CGI-S) Rating Scale at Week 8 | Baseline, 8 weeks | 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. |
| Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Item 8 (Inability to Feel) at Week 8 | Baseline, 8 weeks | 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. |
| Change From Baseline in the Apathy Evaluation Scale-Clinician Rated Version (AES-C) Subscale Scores at Week 8 | Baseline, 8 weeks | 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. |
| Change From Baseline in the Sheehan Disability Scale (SDS) Total and Individual Scores at Week 8 | Baseline, 8 weeks | 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. |
| Percentage of Participants Who Relapsed During 8 Weeks | Baseline through 8 weeks | 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). |
| Number of Days From Baseline to Relapse as Defined by Montgomery-Asberg Depression Rating Scale (MADRS) Total Score ≥16 During 8 Weeks | Baseline through 8 weeks | 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). |
| Percentage of Participants Who Discontinue Due to Lack of Efficacy During 8 Weeks | Baseline through 8 weeks | Percentage of participants who discontinue after baseline due to lack of efficacy in the investigator's opinion. |
| Change From Baseline in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) Total and Item Scores at Week 8 | Baseline, 8 weeks | 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. |
Countries
Australia, Canada, Mexico, Russia, Taiwan
Participant flow
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| 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. | 244 |
| 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. | 239 |
| Total | 483 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 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
| Characteristic | Total | Escitalopram | Duloxetine |
|---|---|---|---|
| Age Continuous | 44.54 years STANDARD_DEVIATION 13.35 | 44.93 years STANDARD_DEVIATION 12.89 | 44.15 years STANDARD_DEVIATION 13.81 |
| Apathy Evaluation Scale - Clinician Rated Version (AES-C) Total Score | 46.31 units on a scale STANDARD_DEVIATION 7.97 | 46.34 units on a scale STANDARD_DEVIATION 8.14 | 46.28 units on a scale STANDARD_DEVIATION 7.82 |
| Clinical Global Impressions of Severity Scale (CGI-S) | 3.05 units on a scale STANDARD_DEVIATION 0.91 | 3.04 units on a scale STANDARD_DEVIATION 0.91 | 3.05 units on a scale STANDARD_DEVIATION 0.91 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 89 Participants | 44 Participants | 45 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 394 Participants | 195 Participants | 199 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Montgomery-Asberg Depression Rating Scale (MADRS) Item 8 Score | 1.82 units on a scale STANDARD_DEVIATION 1.13 | 1.82 units on a scale STANDARD_DEVIATION 1.15 | 1.82 units on a scale STANDARD_DEVIATION 1.1 |
| Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | 10.43 units on a scale STANDARD_DEVIATION 3.59 | 10.29 units on a scale STANDARD_DEVIATION 3.68 | 10.57 units on a scale STANDARD_DEVIATION 3.49 |
| Race (NIH/OMB) American Indian or Alaska Native | 71 participants | 37 participants | 34 participants |
| Race (NIH/OMB) Asian | 172 participants | 82 participants | 90 participants |
| Race (NIH/OMB) Black or African American | 1 participants | 1 participants | 0 participants |
| Race (NIH/OMB) More than one race | 1 participants | 0 participants | 1 participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 participants | 0 participants | 1 participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 participants | 0 participants | 0 participants |
| Race (NIH/OMB) White | 239 participants | 119 participants | 120 participants |
| Region of Enrollment Australia | 49 participants | 25 participants | 24 participants |
| Region of Enrollment Canada | 87 participants | 43 participants | 44 participants |
| Region of Enrollment China | 88 participants | 41 participants | 47 participants |
| Region of Enrollment Italy | 45 participants | 22 participants | 23 participants |
| Region of Enrollment Korea, Republic of | 33 participants | 15 participants | 18 participants |
| Region of Enrollment Mexico | 85 participants | 43 participants | 42 participants |
| Region of Enrollment Russian Federation | 48 participants | 25 participants | 23 participants |
| Region of Enrollment Taiwan | 48 participants | 25 participants | 23 participants |
| Rothschild Scale for Antidepressant Tachyphylaxis (RSAT) Total Score | 10.62 units on a scale STANDARD_DEVIATION 4.93 | 10.51 units on a scale STANDARD_DEVIATION 4.95 | 10.72 units on a scale STANDARD_DEVIATION 4.92 |
| Sex: Female, Male Female | 366 Participants | 179 Participants | 187 Participants |
| Sex: Female, Male Male | 117 Participants | 60 Participants | 57 Participants |
| Sheehan Disability Scale - Total Score (SDS Total) | 14.98 units on a scale STANDARD_DEVIATION 6.58 | 14.62 units on a scale STANDARD_DEVIATION 6.39 | 15.32 units on a scale STANDARD_DEVIATION 6.76 |
| Taking Escitalopram 3 Months Prior to Study Entry No | 357 participants | 180 participants | 177 participants |
| Taking Escitalopram 3 Months Prior to Study Entry Yes | 126 participants | 59 participants | 67 participants |
| The Massachusetts General Hospital Cognitive and Physical functioning Questionnaire (MGH-CPFQ) Total | 24.73 units on a scale STANDARD_DEVIATION 5.78 | 24.69 units on a scale STANDARD_DEVIATION 5.83 | 24.78 units on a scale STANDARD_DEVIATION 5.73 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 130 / 244 | 100 / 239 |
| serious Total, serious adverse events | 3 / 244 | 3 / 239 |
Outcome results
Primary
Change From Baseline in the Apathy Evaluation Scale - Clinician Rated Version (AES-C) Total Score at Week 8
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.
Time frame: Baseline, 8 weeks
Population: All randomized participants with a baseline and at least 1 post-baseline result.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | 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 |
| Escitalopram | Change From Baseline in the Apathy Evaluation Scale - Clinician Rated Version (AES-C) Total Score at Week 8 | -13.50 units on a scale | Standard Error 0.54 |
p-value: 0.61295% CI: [-1.87, 1.1]Mixed Models Analysis
Secondary
Change From Baseline in the Apathy Evaluation Scale-Clinician Rated Version (AES-C) Subscale Scores at Week 8
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.
Time frame: Baseline, 8 weeks
Population: All randomized participants with a baseline and at least 1 post-baseline result.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 0.1 |
| Escitalopram | Change From Baseline in the Apathy Evaluation Scale-Clinician Rated Version (AES-C) Subscale Scores at Week 8 | Other Items Total Score | -2.44 units on a scale | Standard Error 0.1 |
| Escitalopram | Change From Baseline in the Apathy Evaluation Scale-Clinician Rated Version (AES-C) Subscale Scores at Week 8 | Cognition Items Total Score | -6.25 units on a scale | Standard Error 0.26 |
| Escitalopram | Change From Baseline in the Apathy Evaluation Scale-Clinician Rated Version (AES-C) Subscale Scores at Week 8 | Emotional Items Total Score | -1.58 units on a scale | Standard Error 0.08 |
| Escitalopram | Change From Baseline in the Apathy Evaluation Scale-Clinician Rated Version (AES-C) Subscale Scores at Week 8 | Behavior Items Total Score | -3.25 units on a scale | Standard Error 0.16 |
p-value: 0.504Mixed Models Analysis
p-value: 0.665Mixed Models Analysis
p-value: 0.489Mixed Models Analysis
p-value: 0.945Mixed Models Analysis
Secondary
Change From Baseline in the Clinical Global Impression of Severity (CGI-S) Rating Scale at Week 8
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.
Time frame: Baseline, 8 weeks
Population: All randomized participants with a baseline and at least 1 post-baseline result.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | 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 |
| Escitalopram | Change From Baseline in the Clinical Global Impression of Severity (CGI-S) Rating Scale at Week 8 | -0.93 units on a scale | Standard Error 0.06 |
p-value: 0.41Mixed Models Analysis
Secondary
Change From Baseline in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) Total and Item Scores at Week 8
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.
Time frame: Baseline, 8 weeks
Population: All randomized participants with a baseline and at least 1 post-baseline result.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Escitalopram | 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 | -0.85 units on a scale | Standard Error 0.06 |
| Escitalopram | 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 | -1.35 units on a scale | Standard Error 0.07 |
| Escitalopram | 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 | -1.00 units on a scale | Standard Error 0.06 |
| Escitalopram | Change From Baseline in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) Total and Item Scores at Week 8 | Energy Score | -1.21 units on a scale | Standard Error 0.07 |
| Escitalopram | 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 | -1.02 units on a scale | Standard Error 0.06 |
| Escitalopram | 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 | -0.85 units on a scale | Standard Error 0.06 |
| Escitalopram | 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 | -0.71 units on a scale | Standard Error 0.05 |
| Escitalopram | Change From Baseline in the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire (MGH-CPFQ) Total and Item Scores at Week 8 | Total Score | -6.91 units on a scale | Standard Error 0.35 |
p-value: 0.91ANCOVA
p-value: 0.882ANCOVA
p-value: 0.657ANCOVA
p-value: 0.457ANCOVA
p-value: 0.737ANCOVA
p-value: 0.404ANCOVA
p-value: 0.808ANCOVA
p-value: 0.431ANCOVA
Secondary
Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Item 8 (Inability to Feel) at Week 8
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.
Time frame: Baseline, 8 weeks
Population: All randomized participants with a baseline and at least 1 post-baseline result.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | 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 |
| Duloxetine | 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 |
| Escitalopram | Change From Baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) Total Score and Item 8 (Inability to Feel) at Week 8 | Total Score | -4.14 units on a scale | Standard Error 0.33 |
| Escitalopram | 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) | -0.90 units on a scale | Standard Error 0.06 |
p-value: 0.88Mixed Models Analysis
p-value: 0.224Mixed Models Analysis
Secondary
Change From Baseline in the Rothschild Scale for Antidepressant Tachyphylaxis (RSAT) Total and Individual Item Scores at Week 8
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.
Time frame: Baseline, 8 weeks
Population: All randomized participants with a baseline at and least 1 post-baseline result.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Escitalopram | Change From Baseline in the Rothschild Scale for Antidepressant Tachyphylaxis (RSAT) Total and Individual Item Scores at Week 8 | Affect | -0.50 units on a scale | Standard Error 0.04 |
| Escitalopram | Change From Baseline in the Rothschild Scale for Antidepressant Tachyphylaxis (RSAT) Total and Individual Item Scores at Week 8 | RSAT Total Score | -4.98 units on a scale | Standard Error 0.26 |
| Escitalopram | Change From Baseline in the Rothschild Scale for Antidepressant Tachyphylaxis (RSAT) Total and Individual Item Scores at Week 8 | Energy Level | -1.19 units on a scale | Standard Error 0.07 |
| Escitalopram | Change From Baseline in the Rothschild Scale for Antidepressant Tachyphylaxis (RSAT) Total and Individual Item Scores at Week 8 | Motivation and Interest | -1.29 units on a scale | Standard Error 0.06 |
| Escitalopram | Change From Baseline in the Rothschild Scale for Antidepressant Tachyphylaxis (RSAT) Total and Individual Item Scores at Week 8 | Cognitive Functioning | -0.80 units on a scale | Standard Error 0.06 |
| Escitalopram | Change From Baseline in the Rothschild Scale for Antidepressant Tachyphylaxis (RSAT) Total and Individual Item Scores at Week 8 | Weight Gain | -0.11 units on a scale | Standard Error 0.05 |
| Escitalopram | Change From Baseline in the Rothschild Scale for Antidepressant Tachyphylaxis (RSAT) Total and Individual Item Scores at Week 8 | Sleep | -0.55 units on a scale | Standard Error 0.08 |
| Escitalopram | Change From Baseline in the Rothschild Scale for Antidepressant Tachyphylaxis (RSAT) Total and Individual Item Scores at Week 8 | Sexual Functioning | -0.60 units on a scale | Standard Error 0.07 |
p-value: 0.157Mixed Models Analysis
p-value: 0.119Mixed Models Analysis
p-value: 0.184Mixed Models Analysis
p-value: 0.226Mixed Models Analysis
p-value: 0.059Mixed Models Analysis
p-value: 0.466Mixed Models Analysis
p-value: 0.822Mixed Models Analysis
p-value: 0.599Mixed Models Analysis
Secondary
Change From Baseline in the Sheehan Disability Scale (SDS) Total and Individual Scores at Week 8
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.
Time frame: Baseline, 8 weeks
Population: All randomized participants with a baseline and at least 1 post-baseline result.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 |
| Duloxetine | 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 0.4 |
| Escitalopram | Change From Baseline in the Sheehan Disability Scale (SDS) Total and Individual Scores at Week 8 | SDS Days Unproductive Score (N=209, 205) | -1.89 units on a scale | Standard Error 0.13 |
| Escitalopram | Change From Baseline in the Sheehan Disability Scale (SDS) Total and Individual Scores at Week 8 | SDS Work Score | -2.29 units on a scale | Standard Error 0.14 |
| Escitalopram | Change From Baseline in the Sheehan Disability Scale (SDS) Total and Individual Scores at Week 8 | SDS Family Score (N=212, 210) | -2.67 units on a scale | Standard Error 0.16 |
| Escitalopram | Change From Baseline in the Sheehan Disability Scale (SDS) Total and Individual Scores at Week 8 | SDS Social Score (N=212, 210) | -2.72 units on a scale | Standard Error 0.16 |
| Escitalopram | Change From Baseline in the Sheehan Disability Scale (SDS) Total and Individual Scores at Week 8 | SDS Days Lost Score (N=208, 204) | -0.60 units on a scale | Standard Error 0.11 |
| Escitalopram | Change From Baseline in the Sheehan Disability Scale (SDS) Total and Individual Scores at Week 8 | SDS Total Score | -7.67 units on a scale | Standard Error 0.41 |
p-value: 0.821ANCOVA
p-value: 0.491ANCOVA
p-value: 0.451ANCOVA
p-value: 0.443ANCOVA
p-value: 0.719ANCOVA
p-value: 0.517ANCOVA
Secondary
Number of Days From Baseline to Relapse as Defined by Montgomery-Asberg Depression Rating Scale (MADRS) Total Score ≥16 During 8 Weeks
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).
Time frame: 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.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine | 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 |
| Duloxetine | 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 |
| Escitalopram | 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 |
| Escitalopram | 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 | 68.00 days |
Comparison: The log-rank test was conducted using Kaplan-Meier Product-Limit method.p-value: 0.691Log Rank
Secondary
Patient's Global Impressions of Improvement Scale (PGI-I) Rating Scale Score at Week 8
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.
Time frame: 8 weeks
Population: All randomized participants.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Duloxetine | 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 |
| Escitalopram | Patient's Global Impressions of Improvement Scale (PGI-I) Rating Scale Score at Week 8 | 2.55 units on a scale | Standard Error 0.08 |
p-value: 0.723Mixed Models Analysis
Secondary
Percentage of Participants Who Discontinue Due to Lack of Efficacy During 8 Weeks
Percentage of participants who discontinue after baseline due to lack of efficacy in the investigator's opinion.
Time frame: Baseline through 8 weeks
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duloxetine | Percentage of Participants Who Discontinue Due to Lack of Efficacy During 8 Weeks | 2.0 percentage of participants |
| Escitalopram | Percentage of Participants Who Discontinue Due to Lack of Efficacy During 8 Weeks | 1.3 percentage of participants |
p-value: 0.724Fisher Exact
Secondary
Percentage of Participants Who Relapsed During 8 Weeks
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).
Time frame: Baseline through 8 weeks
Population: All randomized participants with a baseline and at least 1 post-baseline result.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Duloxetine | Percentage of Participants Who Relapsed During 8 Weeks | 11.9 percentage of participants |
| Escitalopram | Percentage of Participants Who Relapsed During 8 Weeks | 11.0 percentage of participants |
p-value: 0.776Fisher Exact