Depressive Disorder, Major
Conditions
Brief summary
The purpose of this study is to help answer the following research question: Whether switching to duloxetine improves depressed mood when current treatment did not work well for patients with depression.
Interventions
DRUGDuloxetine
Study Period II (Acute Therapy): 60 mg capsules, QD, for 4 weeks. Study Period III (Optimization): Responder group - 60 mg capsules, QD, for 4 weeks more. Non-responder group - 120 mg capsules, QD, for 4 weeks more.
Sponsors
Eli Lilly and Company
Study design
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female outpatients aged 18 years or older who meet criteria for Major Depressive Disorder (MDD). * Currently receiving a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI) class of antidepressant for at least a month for the treatment of depression. * Females of child-bearing potential (not surgically sterilized and between menarche and 1 year postmenopause) to test negative for pregnancy based on a urine pregnancy test and to agree to use a reliable method of birth control.
Exclusion criteria
* Women who are pregnant or plan to be pregnant or are breastfeeding. * To have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication. * Diagnosed with treatment resistant depression. * History of bipolar disorder, schizophrenia, or other psychotic disorders. * To have previously taken duloxetine that didn't work. * Judged to be at serious suicidal risk in the opinion of the investigator and/or score \>=3 on Item 3 (suicide) of the 17-Item Hamilton Depression Rating Scale (HAMD-17) at screening (Visit 1) or baseline (Visit 2). * A serious medical illness that may need treatment during the study. * Taking certain medications that are not allowed in this study. * To have a history of alcohol and/or drug abuse or dependence within the past year. * To have uncontrolled narrow-angle glaucoma. * To have allergic reactions to many medicines. * To have undergone shock therapy (Electroconvulsive Therapy) or magnet treatment (Transcranial Magnetic Stimulation) within the past year. * To initiate talk therapy (psychotherapy) just before or during the study. * To have chronic pain and you have been taking medicine for it for the last 6 months. * To have certain liver diseases. * To have kidney disease or undergoing dialysis. * Abnormal thyroid stimulating hormone (TSH) concentration.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Brief Pain Inventory-Modified Short Form (BPI-SF) Interference Score Between Responder and Non-Responder Participants at 4 Weeks | Baseline, 4 weeks | BPI-SF interference score asks about the degree to which pain interferes with mood, walking and other physical activity, work, social activity, relations with others, and sleep. BPI-SF interference score ranges from 0 (no interference) to 10 (interferes completely). Response is defined as a \>=50% reduction in the Maier subscale score from baseline. The Maier subscale (Items 1,2,7,8,9,10) represents core symptoms of depression. Total subscale scores range from 0 (normal) to 24 (severe). Factors used for adjustment for least squares means are listed in 'Other relevant information' section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Treatment Satisfaction Questionnaire for Medication (TSQM) at 4 and 8 Weeks | Baseline, 4 weeks, 8 weeks | The TSQM is a participant-reported measure that best describes how the study medication makes them feel since the last study visit, assessing perceived effectiveness, severity of side effects, and convenience. Convenience, Effectiveness, Side-Effects, and Global Satisfaction scale scores range from 0 (extremely dissatisfied) to 100 (extremely satisfied). Factors used for adjustment for least squares means are listed in 'Other relevant information' section. |
| Percentage of Participants Meeting Criteria for Response on the 17-Item Hamilton Depression Rating Scale (HAMD-17) Maier Subscale at 4 and 8 Weeks | Baseline, 4 weeks, 8 weeks | The Maier subscale (Items 1,2,7,8,9,10) represents the core symptoms of depression. Total subscale scores range from 0 (normal) to 24 (severe). Response is defined as a \>=50% reduction in the Maier subscale score from baseline. |
| Change From Baseline HAMD-17 Total Score at 8 Weeks | Baseline, 8 weeks | The HAMD-17 total score 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). Factors used for adjustment for least squares means are listed in 'Other relevant information' section. |
| Change From Baseline HAMD-17 Core Subscale at 8 Weeks | Baseline, 8 weeks | The Core subscale (Items 1,2,3,7,8) evaluates core symptoms of depression. Total subscale scores range from 0 (normal) to 20 (severe). Factors used for adjustment for least squares means are listed in 'Other relevant information' section. |
| Change From Baseline HAMD-17 Maier Subscale at 8 Weeks | Baseline, 8 weeks | The Maier subscale (Items 1,2,7,8,9,10) represents the core symptoms of depression. Total subscale scores range from 0 (normal) to 24 (severe). Factors used for adjustment for least squares means are listed in 'Other relevant information' section. |
| Change From Baseline HAMD-17 Anxiety/Somatization Subscale at 8 Weeks | Baseline, 8 weeks | The Anxiety/Somatization Subscale (Items 10-13, 15, 17) evaluates severity of psychic and somatic manifistations of anxiety as well as agitation. Total subscale scores range from 0 (normal) to 18 (severe). Factors used for adjustment for least squares means are listed in 'Other relevant information' section. |
| Change From Baseline in the Sexual Functioning Questionnaire Clinical Version (CSFQ) at 4 and 8 Weeks | Baseline, 4 Weeks, 8 weeks | A 14-item patient-rated scale assesses medication-related changes in sexual activity/functioning. Items rated from 1 (never, low enjoyment/pleasure) to 5 (every day, great enjoyment/pleasure). CSFQ measures 5 dimensions of sexual behavior: pleasure; desire/frequency; desire/interest; arousal; orgasm. Lower total scores are associated with diminished sexual functioning. Total scores \<=47 (men) and \<=41 (women) indicate global sexual dysfunction, with all phases of sexual response cycle affected. Factors used for adjustment for least squares means are in 'Other relevant information' section. |
| Change From Baseline HAMD-17 Sleep Subscale at 8 Weeks | Baseline, 8 weeks | The Sleep Subscale (Items 4,5,6) evaluates initial, middle, and late insomnia. Total subscale scores range from 0 (no difficulty) to 6 (difficulty). Factors used for adjustment for least squares means are listed in 'Other relevant information' section. |
| Change From Baseline in the Hamilton Anxiety Rating Scale (HAMA) at 8 Weeks | Baseline, 8 weeks | The HAMA scale measures anxiety symptoms accompanying major depressive disorder (MDD). Each item of the 14-item HAMA was scored from 0 (not present) to 4 (very severe), with a resulting maximum total score of 56. Factors used for adjustment for least squares means are listed in 'Other relevant information' section. |
| Change From Baseline in the Clinical Global Impression - Severity (CGI-Severity) Scale at 8 Weeks | Baseline, 8 weeks | 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). Factors used for adjustment for least squares means are listed in 'Other relevant information' section. |
| Change From Baseline in the Brief Pain Inventory - Modified Short Form (BPI-SF) Average Pain Score at 8 Weeks | Baseline, 8 weeks | A self-reported scale that measures the severity of pain based on the average pain experienced over the past 24-hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). Factors used for adjustment for least squares means are listed in 'Other relevant information' section. |
| Change From Baseline in Patient Global Impression - Improvement (PGI-I) Scale Score at 8 Weeks | 8 weeks | A scale that measures the patient'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). Factors used for adjustment for least squares means are listed in 'Other relevant information' section. |
| Change From Baseline in the Sheehan Disability Scale (SDS) at 4 and 8 Weeks | Baseline, 4 weeks, 8 weeks | The SDS is completed by the patient and is used to assess the effect of the patient's symptoms on their work/social/family life. Total scores range from 0 to 30 with higher values indicating greater disruption in the patient's work/social/family life. Factors used for adjustment for least squares means are listed in 'Other relevant information' section. |
| Change From Baseline HAMD-17 Retardation/Somatization Subscale at 8 Weeks | Baseline, 8 weeks | The Retardation Subscale (Items 1,7,8,14) evaluates dysfunction in mood, work, and sexual activity, as well as overall motor retardation. Total subscale scores range from 0 (normal) to 14 (severe). Factors used for adjustment for least squares means are listed in 'Other relevant information' section. |
Countries
South Korea
Participant flow
Pre-assignment details
270 participants began the study. 26 were screen failures (17 did not meet entry criteria, 7 decided to withdraw, and 2 withdrew based on the physician's decision). 2 participants discontinued before enrollment (1 was lost to follow-up and 1 decided to withdraw).
Participants by arm
| Arm | Count |
|---|---|
| Duloxetine Responders 60 milligram (mg) duloxetine capsules, once daily (QD), for 4 weeks (Study Period II). Responder group - 60 mg capsules, QD, for 4 weeks more (Study Period III). | 115 |
| Duloxetine Non-Responders 60 mg duloxetine capsules, QD, for 4 weeks (Study Period II). Non-responder group - 120 mg capsules, QD, for 4 weeks more (Study Period III). | 91 |
| Unclassified Participants who received 60 milligram (mg) duloxetine capsules, once daily (QD), for 4 weeks (Study Period II) with unknown response status. | 36 |
| Total | 242 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Period II | Adverse Event | 0 | 0 | 15 |
| Period II | Lack of Efficacy | 0 | 0 | 2 |
| Period II | Lost to Follow-up | 0 | 0 | 4 |
| Period II | Protocol Violation | 0 | 0 | 11 |
| Period II | Sponsor Decision | 0 | 0 | 0 |
| Period II | Withdrawal by Subject | 0 | 0 | 4 |
| Period III | Adverse Event | 1 | 1 | 0 |
| Period III | Lack of Efficacy | 0 | 2 | 0 |
| Period III | Lost to Follow-up | 2 | 1 | 0 |
| Period III | Protocol Violation | 1 | 1 | 0 |
| Period III | Sponsor Decision | 2 | 0 | 0 |
| Period III | Withdrawal by Subject | 1 | 2 | 0 |
Baseline characteristics
| Characteristic | Total | Duloxetine Responders | Duloxetine Non-Responders | Unclassified |
|---|---|---|---|---|
| 17-Item Hamilton Depression Rating Scale (HAMD-17) Anxiety/Somatization Score | 7.8 units on a scale STANDARD_DEVIATION 2 | 7.7 units on a scale STANDARD_DEVIATION 2.1 | 8.0 units on a scale STANDARD_DEVIATION 2 | 7.4 units on a scale STANDARD_DEVIATION 1.7 |
| 17-Item Hamilton Depression Rating Scale (HAMD-17) Core Score | 8.4 units on a scale STANDARD_DEVIATION 2.7 | 8.1 units on a scale STANDARD_DEVIATION 2.6 | 9.0 units on a scale STANDARD_DEVIATION 2.6 | 7.9 units on a scale STANDARD_DEVIATION 2.8 |
| 17-Item Hamilton Depression Rating Scale (HAMD-17) Maier Score | 11.0 units on a scale STANDARD_DEVIATION 2.7 | 10.7 units on a scale STANDARD_DEVIATION 2.6 | 11.7 units on a scale STANDARD_DEVIATION 2.6 | 10.0 units on a scale STANDARD_DEVIATION 2.7 |
| 17-Item Hamilton Depression Rating Scale (HAMD-17) Retardation Score | 7.5 units on a scale STANDARD_DEVIATION 2.1 | 7.1 units on a scale STANDARD_DEVIATION 2.1 | 8.2 units on a scale STANDARD_DEVIATION 1.9 | 7.2 units on a scale STANDARD_DEVIATION 2.4 |
| 17-Item Hamilton Depression Rating Scale (HAMD-17) Sleep Score | 3.2 units on a scale STANDARD_DEVIATION 1.5 | 3.1 units on a scale STANDARD_DEVIATION 1.6 | 3.4 units on a scale STANDARD_DEVIATION 1.4 | 3.2 units on a scale STANDARD_DEVIATION 1.7 |
| 17-Item Hamilton Depression Rating Scale (HAMD-17) Total Score | 21.9 units on a scale STANDARD_DEVIATION 4.6 | 21.3 units on a scale STANDARD_DEVIATION 4.5 | 23.3 units on a scale STANDARD_DEVIATION 4.5 | 20.7 units on a scale STANDARD_DEVIATION 4.5 |
| Age Continuous | 44.9 years STANDARD_DEVIATION 12.5 | 43.5 years STANDARD_DEVIATION 12.9 | 45.6 years STANDARD_DEVIATION 12.5 | 47.4 years STANDARD_DEVIATION 10.6 |
| Age of First Episode of MDD | 34.8 years STANDARD_DEVIATION 12.6 | 35.2 years STANDARD_DEVIATION 11.7 | 33.5 years STANDARD_DEVIATION 13.6 | 36.9 years STANDARD_DEVIATION 12.8 |
| Brief Pain Inventory - Short Form (BPI-SF) Average Pain Score | 4.8 Units on a scale STANDARD_DEVIATION 2 | 4.7 Units on a scale STANDARD_DEVIATION 1.9 | 5.0 Units on a scale STANDARD_DEVIATION 2 | 4.4 Units on a scale STANDARD_DEVIATION 2.2 |
| Brief Pain Inventory - Short Form Interference Score | 5.5 Units on a scale STANDARD_DEVIATION 1.8 | 5.2 Units on a scale STANDARD_DEVIATION 1.6 | 5.9 Units on a scale STANDARD_DEVIATION 1.8 | 5.2 Units on a scale STANDARD_DEVIATION 1.9 |
| Changes in Sexual Function Questionnaire (CSFQ) | 35.1 Units on a scale STANDARD_DEVIATION 10 | 35.3 Units on a scale STANDARD_DEVIATION 10.3 | 35.4 Units on a scale STANDARD_DEVIATION 9.8 | 33.8 Units on a scale STANDARD_DEVIATION 9.4 |
| Clinical Global Impressions - Severity (CGI-Severity) Score | 4.3 Units on a scale STANDARD_DEVIATION 0.6 | 4.2 Units on a scale STANDARD_DEVIATION 0.6 | 4.4 Units on a scale STANDARD_DEVIATION 0.6 | 4.3 Units on a scale STANDARD_DEVIATION 0.7 |
| Duration of the Current Episode | 247.3 days STANDARD_DEVIATION 333.3 | 249.4 days STANDARD_DEVIATION 378.3 | 264.5 days STANDARD_DEVIATION 318.1 | 194.1 days STANDARD_DEVIATION 182.6 |
| Had at Least One Historical Illness No | 151 participants | 71 participants | 59 participants | 21 participants |
| Had at Least One Historical Illness Yes | 91 participants | 44 participants | 32 participants | 15 participants |
| Had Major Depressive Disorder (MDD) Hospitalizations in the Past 24 Months No | 227 participants | 107 participants | 86 participants | 34 participants |
| Had Major Depressive Disorder (MDD) Hospitalizations in the Past 24 Months Yes | 15 participants | 8 participants | 5 participants | 2 participants |
| Had Previous MDD in the Past 24 Months No | 85 participants | 36 participants | 37 participants | 12 participants |
| Had Previous MDD in the Past 24 Months Yes | 157 participants | 79 participants | 54 participants | 24 participants |
| Hamilton Anxiety Rating Scale (HAMA) Total Score | 19.2 Units on a scale STANDARD_DEVIATION 7.1 | 17.9 Units on a scale STANDARD_DEVIATION 6.8 | 21.4 Units on a scale STANDARD_DEVIATION 6.8 | 17.9 Units on a scale STANDARD_DEVIATION 7.6 |
| Number of MDD Hospitalizations in the Past 24 Months | 1.0 hospitalizations STANDARD_DEVIATION 0 | 1.0 hospitalizations STANDARD_DEVIATION 0 | 1.0 hospitalizations STANDARD_DEVIATION 0 | 1.0 hospitalizations STANDARD_DEVIATION 0 |
| Number of Previous MDD Episodes in the Past 24 Months | 1.6 MDD episodes STANDARD_DEVIATION 0.9 | 1.6 MDD episodes STANDARD_DEVIATION 0.8 | 1.5 MDD episodes STANDARD_DEVIATION 0.7 | 1.8 MDD episodes STANDARD_DEVIATION 1.5 |
| Previous Treatment Missing or Unknown | 4 participants | 1 participants | 1 participants | 2 participants |
| Previous Treatment SNRI | 61 participants | 31 participants | 21 participants | 9 participants |
| Previous Treatment SSRI | 177 participants | 83 participants | 69 participants | 25 participants |
| Race/Ethnicity, Customized African | 3 participants | 1 participants | 0 participants | 2 participants |
| Race/Ethnicity, Customized Caucasian | 150 participants | 67 participants | 66 participants | 17 participants |
| Race/Ethnicity, Customized East Asian | 78 participants | 43 participants | 23 participants | 12 participants |
| Race/Ethnicity, Customized Hispanic | 7 participants | 2 participants | 2 participants | 3 participants |
| Race/Ethnicity, Customized West Asian | 4 participants | 2 participants | 0 participants | 2 participants |
| Region of Enrollment Brazil | 33 participants | 9 participants | 11 participants | 13 participants |
| Region of Enrollment Canada | 130 participants | 63 participants | 56 participants | 11 participants |
| Region of Enrollment China | 41 participants | 25 participants | 13 participants | 3 participants |
| Region of Enrollment Korea, Republic of | 38 participants | 18 participants | 11 participants | 9 participants |
| Sex: Female, Male Female | 182 Participants | 88 Participants | 64 Participants | 30 Participants |
| Sex: Female, Male Male | 60 Participants | 27 Participants | 27 Participants | 6 Participants |
| Sheehan Disability Scale (SDS) | 5.7 Units on a scale STANDARD_DEVIATION 3 | 5.4 Units on a scale STANDARD_DEVIATION 2.9 | 6.3 Units on a scale STANDARD_DEVIATION 3 | 5.5 Units on a scale STANDARD_DEVIATION 3 |
| Treatment Satisfaction Questionnaire for Medication (TSQM) | 43.7 Units on a scale STANDARD_DEVIATION 18.3 | 44.2 Units on a scale STANDARD_DEVIATION 17.6 | 41.6 Units on a scale STANDARD_DEVIATION 18.2 | 47.2 Units on a scale STANDARD_DEVIATION 20.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 71 / 115 | 59 / 91 | 22 / 35 |
| serious Total, serious adverse events | 0 / 115 | 2 / 91 | 0 / 35 |
Outcome results
Primary
Change From Baseline in Brief Pain Inventory-Modified Short Form (BPI-SF) Interference Score Between Responder and Non-Responder Participants at 4 Weeks
BPI-SF interference score asks about the degree to which pain interferes with mood, walking and other physical activity, work, social activity, relations with others, and sleep. BPI-SF interference score ranges from 0 (no interference) to 10 (interferes completely). Response is defined as a \>=50% reduction in the Maier subscale score from baseline. The Maier subscale (Items 1,2,7,8,9,10) represents core symptoms of depression. Total subscale scores range from 0 (normal) to 24 (severe). Factors used for adjustment for least squares means are listed in 'Other relevant information' section.
Time frame: Baseline, 4 weeks
Population: Efficacy Population: Participants who had at least one post-baseline observation were included in the efficacy analysis. The group Unclassified was excluded from statistical testing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Duloxetine Responders | Change From Baseline in Brief Pain Inventory-Modified Short Form (BPI-SF) Interference Score Between Responder and Non-Responder Participants at 4 Weeks | -2.35 Units on a scale |
| Duloxetine Non-Responders | Change From Baseline in Brief Pain Inventory-Modified Short Form (BPI-SF) Interference Score Between Responder and Non-Responder Participants at 4 Weeks | -1.69 Units on a scale |
p-value: 0.00595% CI: [-1.12, -0.2]Adjusted Repeated Measures Analysis
Secondary
Change From Baseline HAMD-17 Anxiety/Somatization Subscale at 8 Weeks
The Anxiety/Somatization Subscale (Items 10-13, 15, 17) evaluates severity of psychic and somatic manifistations of anxiety as well as agitation. Total subscale scores range from 0 (normal) to 18 (severe). Factors used for adjustment for least squares means are listed in 'Other relevant information' section.
Time frame: Baseline, 8 weeks
Population: Efficacy Population: Participants who had at least one post-baseline observation were included in the efficacy analysis. The group Unclassified was excluded from statistical testing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Duloxetine Responders | Change From Baseline HAMD-17 Anxiety/Somatization Subscale at 8 Weeks | -5.29 Units on a scale |
| Duloxetine Non-Responders | Change From Baseline HAMD-17 Anxiety/Somatization Subscale at 8 Weeks | -3.07 Units on a scale |
95% CI: [-2.89, -1.54]Adjusted Repeated Measures Analysis
Secondary
Change From Baseline HAMD-17 Core Subscale at 8 Weeks
The Core subscale (Items 1,2,3,7,8) evaluates core symptoms of depression. Total subscale scores range from 0 (normal) to 20 (severe). Factors used for adjustment for least squares means are listed in 'Other relevant information' section.
Time frame: Baseline, 8 weeks
Population: Efficacy Population: Participants who had at least one post-baseline observation were included in the efficacy analysis. The group Unclassified was excluded from statistical testing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Duloxetine Responders | Change From Baseline HAMD-17 Core Subscale at 8 Weeks | -6.87 Units on a scale |
| Duloxetine Non-Responders | Change From Baseline HAMD-17 Core Subscale at 8 Weeks | -4.40 Units on a scale |
95% CI: [-3.13, -1.81]Adjusted Repeated Measures Analysis
Secondary
Change From Baseline HAMD-17 Maier Subscale at 8 Weeks
The Maier subscale (Items 1,2,7,8,9,10) represents the core symptoms of depression. Total subscale scores range from 0 (normal) to 24 (severe). Factors used for adjustment for least squares means are listed in 'Other relevant information' section.
Time frame: Baseline, 8 weeks
Population: Efficacy Population: Participants who had at least one post-baseline observation were included in the efficacy analysis. The group Unclassified was excluded from statistical testing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Duloxetine Responders | Change From Baseline HAMD-17 Maier Subscale at 8 Weeks | -8.58 Units on a scale |
| Duloxetine Non-Responders | Change From Baseline HAMD-17 Maier Subscale at 8 Weeks | -5.29 Units on a scale |
95% CI: [-4.1, -2.48]Adjusted Repeated Measures Analysis
Secondary
Change From Baseline HAMD-17 Retardation/Somatization Subscale at 8 Weeks
The Retardation Subscale (Items 1,7,8,14) evaluates dysfunction in mood, work, and sexual activity, as well as overall motor retardation. Total subscale scores range from 0 (normal) to 14 (severe). Factors used for adjustment for least squares means are listed in 'Other relevant information' section.
Time frame: Baseline, 8 weeks
Population: Efficacy Population: Participants who had at least one post-baseline observation were included in the efficacy analysis. The group Unclassified was excluded from statistical testing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Duloxetine Responders | Change From Baseline HAMD-17 Retardation/Somatization Subscale at 8 Weeks | -5.51 Units on a scale |
| Duloxetine Non-Responders | Change From Baseline HAMD-17 Retardation/Somatization Subscale at 8 Weeks | -3.63 Units on a scale |
95% CI: [-2.45, -1.3]Adjusted Repeated Measures Analysis
Secondary
Change From Baseline HAMD-17 Sleep Subscale at 8 Weeks
The Sleep Subscale (Items 4,5,6) evaluates initial, middle, and late insomnia. Total subscale scores range from 0 (no difficulty) to 6 (difficulty). Factors used for adjustment for least squares means are listed in 'Other relevant information' section.
Time frame: Baseline, 8 weeks
Population: Efficacy Population: Participants who had at least one post-baseline observation were included in the efficacy analysis. The group Unclassified was excluded from statistical testing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Duloxetine Responders | Change From Baseline HAMD-17 Sleep Subscale at 8 Weeks | -2.27 Units on a scale |
| Duloxetine Non-Responders | Change From Baseline HAMD-17 Sleep Subscale at 8 Weeks | -1.31 Units on a scale |
95% CI: [-1.31, -0.63]Adjusted Repeated Measures Analysis
Secondary
Change From Baseline HAMD-17 Total Score at 8 Weeks
The HAMD-17 total score 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). Factors used for adjustment for least squares means are listed in 'Other relevant information' section.
Time frame: Baseline, 8 weeks
Population: Efficacy Population: Participants who had at least one post-baseline observation were included in the efficacy analysis. The group Unclassified was excluded from statistical testing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Duloxetine Responders | Change From Baseline HAMD-17 Total Score at 8 Weeks | -15.64 Units on a scale |
| Duloxetine Non-Responders | Change From Baseline HAMD-17 Total Score at 8 Weeks | -9.79 Units on a scale |
95% CI: [-7.34, -4.36]Adjusted Repeated Measures Analysis
Secondary
Change From Baseline in Patient Global Impression - Improvement (PGI-I) Scale Score at 8 Weeks
A scale that measures the patient'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). Factors used for adjustment for least squares means are listed in 'Other relevant information' section.
Time frame: 8 weeks
Population: Efficacy Population: Participants who had at least one post-baseline observation were included in the efficacy analysis. The group Unclassified was excluded from statistical testing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Duloxetine Responders | Change From Baseline in Patient Global Impression - Improvement (PGI-I) Scale Score at 8 Weeks | 2.12 Units on a scale |
| Duloxetine Non-Responders | Change From Baseline in Patient Global Impression - Improvement (PGI-I) Scale Score at 8 Weeks | 2.61 Units on a scale |
95% CI: [-0.81, -0.18]Adjusted Repeated Measures Analysis
Secondary
Change From Baseline in the Brief Pain Inventory - Modified Short Form (BPI-SF) Average Pain Score at 8 Weeks
A self-reported scale that measures the severity of pain based on the average pain experienced over the past 24-hours. The severity scores range from 0 (no pain) to 10 (pain as severe as you can imagine). Factors used for adjustment for least squares means are listed in 'Other relevant information' section.
Time frame: Baseline, 8 weeks
Population: Efficacy Population: Participants who had at least one post-baseline observation were included in the efficacy analysis. The group Unclassified was excluded from statistical testing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Duloxetine Responders | Change From Baseline in the Brief Pain Inventory - Modified Short Form (BPI-SF) Average Pain Score at 8 Weeks | -2.56 Units on a scale |
| Duloxetine Non-Responders | Change From Baseline in the Brief Pain Inventory - Modified Short Form (BPI-SF) Average Pain Score at 8 Weeks | -2.14 Units on a scale |
95% CI: [-1.08, -0.24]Adjusted Repeated Measures Analysis
Secondary
Change From Baseline in the Clinical Global Impression - Severity (CGI-Severity) Scale at 8 Weeks
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). Factors used for adjustment for least squares means are listed in 'Other relevant information' section.
Time frame: Baseline, 8 weeks
Population: Efficacy Population: Participants who had at least one post-baseline observation were included in the efficacy analysis. The group Unclassified was excluded from statistical testing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Duloxetine Responders | Change From Baseline in the Clinical Global Impression - Severity (CGI-Severity) Scale at 8 Weeks | -2.52 Units on a scale |
| Duloxetine Non-Responders | Change From Baseline in the Clinical Global Impression - Severity (CGI-Severity) Scale at 8 Weeks | -1.40 Units on a scale |
95% CI: [-1.42, -0.84]Adjusted Repeated Measures Analysis
Secondary
Change From Baseline in the Hamilton Anxiety Rating Scale (HAMA) at 8 Weeks
The HAMA scale measures anxiety symptoms accompanying major depressive disorder (MDD). Each item of the 14-item HAMA was scored from 0 (not present) to 4 (very severe), with a resulting maximum total score of 56. Factors used for adjustment for least squares means are listed in 'Other relevant information' section.
Time frame: Baseline, 8 weeks
Population: Efficacy Population: Participants who had at least one post-baseline observation were included in the efficacy analysis. The group Unclassified was excluded from statistical testing.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Duloxetine Responders | Change From Baseline in the Hamilton Anxiety Rating Scale (HAMA) at 8 Weeks | -12.97 Units on a scale |
| Duloxetine Non-Responders | Change From Baseline in the Hamilton Anxiety Rating Scale (HAMA) at 8 Weeks | -8.55 Units on a scale |
95% CI: [-6.04, -2.8]Adjusted Repeated Measures Analysis
Secondary
Change From Baseline in the Sexual Functioning Questionnaire Clinical Version (CSFQ) at 4 and 8 Weeks
A 14-item patient-rated scale assesses medication-related changes in sexual activity/functioning. Items rated from 1 (never, low enjoyment/pleasure) to 5 (every day, great enjoyment/pleasure). CSFQ measures 5 dimensions of sexual behavior: pleasure; desire/frequency; desire/interest; arousal; orgasm. Lower total scores are associated with diminished sexual functioning. Total scores \<=47 (men) and \<=41 (women) indicate global sexual dysfunction, with all phases of sexual response cycle affected. Factors used for adjustment for least squares means are in 'Other relevant information' section.
Time frame: Baseline, 4 Weeks, 8 weeks
Population: Efficacy Population: Participants who had at least one post-baseline observation were included in the efficacy analysis. The group Unclassified was excluded from statistical testing.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Duloxetine Responders | Change From Baseline in the Sexual Functioning Questionnaire Clinical Version (CSFQ) at 4 and 8 Weeks | Week 4 | 0.03 Units on a scale |
| Duloxetine Responders | Change From Baseline in the Sexual Functioning Questionnaire Clinical Version (CSFQ) at 4 and 8 Weeks | Week 8 | 1.08 Units on a scale |
| Duloxetine Non-Responders | Change From Baseline in the Sexual Functioning Questionnaire Clinical Version (CSFQ) at 4 and 8 Weeks | Week 4 | -0.78 Units on a scale |
| Duloxetine Non-Responders | Change From Baseline in the Sexual Functioning Questionnaire Clinical Version (CSFQ) at 4 and 8 Weeks | Week 8 | -0.29 Units on a scale |
Comparison: Week 495% CI: [-0.99, 2.6]Adjusted Repeated Measures Analysis
Comparison: Week 895% CI: [-0.69, 3.42]Adjusted Repeated Measures Analysis
Secondary
Change From Baseline in the Sheehan Disability Scale (SDS) at 4 and 8 Weeks
The SDS is completed by the patient and is used to assess the effect of the patient's symptoms on their work/social/family life. Total scores range from 0 to 30 with higher values indicating greater disruption in the patient's work/social/family life. Factors used for adjustment for least squares means are listed in 'Other relevant information' section.
Time frame: Baseline, 4 weeks, 8 weeks
Population: Efficacy Population: Participants who had at least one post-baseline observation were included in the efficacy analysis. The group Unclassified was excluded from statistical testing.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Duloxetine Responders | Change From Baseline in the Sheehan Disability Scale (SDS) at 4 and 8 Weeks | Week 4 | -8.38 Units on a scale |
| Duloxetine Responders | Change From Baseline in the Sheehan Disability Scale (SDS) at 4 and 8 Weeks | Week 8 | -9.95 Units on a scale |
| Duloxetine Non-Responders | Change From Baseline in the Sheehan Disability Scale (SDS) at 4 and 8 Weeks | Week 4 | -2.49 Units on a scale |
| Duloxetine Non-Responders | Change From Baseline in the Sheehan Disability Scale (SDS) at 4 and 8 Weeks | Week 8 | -5.36 Units on a scale |
Comparison: Week 495% CI: [-7.75, -4.02]Adjusted Repeated Measures Analysis
Comparison: Week 895% CI: [-6.65, -2.54]Adjusted Repeated Measures Analysis
Secondary
Change From Baseline in the Treatment Satisfaction Questionnaire for Medication (TSQM) at 4 and 8 Weeks
The TSQM is a participant-reported measure that best describes how the study medication makes them feel since the last study visit, assessing perceived effectiveness, severity of side effects, and convenience. Convenience, Effectiveness, Side-Effects, and Global Satisfaction scale scores range from 0 (extremely dissatisfied) to 100 (extremely satisfied). Factors used for adjustment for least squares means are listed in 'Other relevant information' section.
Time frame: Baseline, 4 weeks, 8 weeks
Population: Efficacy Population: Participants who had at least one post-baseline observation were included in the efficacy analysis. The group Unclassified was excluded from statistical testing.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Duloxetine Responders | Change From Baseline in the Treatment Satisfaction Questionnaire for Medication (TSQM) at 4 and 8 Weeks | Week 4 | 17.64 Units on a scale |
| Duloxetine Responders | Change From Baseline in the Treatment Satisfaction Questionnaire for Medication (TSQM) at 4 and 8 Weeks | Week 8 | 18.67 Units on a scale |
| Duloxetine Non-Responders | Change From Baseline in the Treatment Satisfaction Questionnaire for Medication (TSQM) at 4 and 8 Weeks | Week 4 | 2.59 Units on a scale |
| Duloxetine Non-Responders | Change From Baseline in the Treatment Satisfaction Questionnaire for Medication (TSQM) at 4 and 8 Weeks | Week 8 | 8.19 Units on a scale |
Comparison: Week 495% CI: [10.63, 19.47]Adjusted Repeated Measures Analysis
Comparison: Week 895% CI: [4.72, 16.24]Adjusted Repeated Measures Analysis
Secondary
Percentage of Participants Meeting Criteria for Response on the 17-Item Hamilton Depression Rating Scale (HAMD-17) Maier Subscale at 4 and 8 Weeks
The Maier subscale (Items 1,2,7,8,9,10) represents the core symptoms of depression. Total subscale scores range from 0 (normal) to 24 (severe). Response is defined as a \>=50% reduction in the Maier subscale score from baseline.
Time frame: Baseline, 4 weeks, 8 weeks
Population: Efficacy Population: Participants who had at least one post-baseline observation were included in the efficacy analysis. The group Unclassified was excluded from statistical testing.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine Responders | Percentage of Participants Meeting Criteria for Response on the 17-Item Hamilton Depression Rating Scale (HAMD-17) Maier Subscale at 4 and 8 Weeks | Week 4 (n=193) | 56.0 Percentage of participants |
| Duloxetine Responders | Percentage of Participants Meeting Criteria for Response on the 17-Item Hamilton Depression Rating Scale (HAMD-17) Maier Subscale at 4 and 8 Weeks | Week 8 (n=179) | 73.7 Percentage of participants |