Major Depressive Disorder
Conditions
Brief summary
An eight-week, randomized, double blind, two parallel groups, study to assess clinical response of duloxetine 60 milligrams (mg) and 120 mg per day in patients hospitalized for severe depression.
Interventions
DRUGDuloxetine hydrochloride
60 mg once or twice a day, by mouth
DRUGPlacebo
placebo capsule by mouth
Sponsors
Boehringer Ingelheim
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Male or female patients of ≥ 18 years of age that meet criteria for severe Major Depressive Disorder, without psychotic features (according to Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, \[DSM-IV\] and confirmed by Mini International Neuropsychiatric Interview \[MINI\]). * With a total score Montgomery-Asberg Depression Rating Scale (MADRS) ≥ 30 and 6-item Hamilton Depression Rating Scale (HAMD-6) ≥ 12 and Clinical Global Impression of Severity (CGI-Severity) ≥ 4 at both screening and baseline. * Requirement of hospitalization (not for social or other non-medical reasons) at screening visit and at least up to Visit 4. * Patients willing and able to comply with the requirement for hospitalization and with all scheduled visits, tests and procedures required by the protocol. * Informed consent document must be signed at screening visit, in accordance with Good Clinical Practice (GCP) and local regulatory requirements, prior to any study procedure.
Exclusion criteria
* More than two previous episodes of major depression that did not respond (according to investigator's opinion) to adequate doses and duration of two different antidepressant therapies. * Lack of response to at least two antidepressant therapies given at adequate doses for at least 6 weeks for the current depressive episode. * Concurrent presence of symptoms fulfilling criteria for any Axis I disorder other than anxiety disorders (with exception of the Obsessive-Compulsive Disorder (OCD)) or Major Depressive Disorder, in the investigator's judgment. * Any previous diagnosis of a bipolar disorder, schizophrenia or OCD. * Depression with catatonic features (according to DSM-IV), depression with post-partum onset, or organic mental disorders. * The presence of an Axis II disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 4 Week Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Baseline to Week 4 | Measures the overall severity of depressive 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Baseline to Weeks 1, 2, 3, 4, 6, 8 | Measures the overall severity of depressive 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). |
| Evaluation of Rescue Options Based on Changes in the Montgomery-Asberg Depression Rating Scale (MADRS) and the 6-Item Hamilton Depression Scale (HAMD-6) | 4 to 8 weeks | Changes in Montgomery-Åsberg Depression Rating Scale (MADRS) and 6-Item Hamilton Depression Scale (HAMD-6) total scores were evaluated following dose up-titration in those patients who did not achieve the minimum 50% response for primary endpoint. MADRS is a rating scale for severity of depressive mood symptoms. Total scores range from 0 (low severity of symptoms) to 60 (high severity of symptoms). The HAMD-6, derived by the sum of HAMD-17 items 1, 2, 7, 8, 10 and 13, evaluates core symptoms of Major Depressive Disorder (MDD). Total subscale scores range from 0 (normal) to 22 (severe). |
| Clinical Global Impression of Severity (CGI-S) Scores at Each Visit | Baseline, Weeks 1, 2, 3, 4, 6, 8 | 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). |
| Clinical Global Impression of Improvement (CGI-I) at Each Visit | Weeks 1, 2, 3, 4, 6, 8 | Measures clinician's perception of patient improvement at the time of assessment compared with the start of treatment. Scores range from 1 (very much better) to 7 (very much worse). |
| Patient Global Impression of Improvement (PGI-I) Score at Each Visit | Weeks 1, 2, 3, 4, 6, 8 | 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). |
| Hamilton Anxiety Scale (HAMA) Score at Baseline and Weeks 4 and 8 | Baseline and Weeks 4 and 8 | 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. |
| Percentage of Responders | 4 to 8 weeks | Patients with reduction in MADRS score ≥50% after 4 weeks were to stay on previous dose of duloxetine. Those with reduction in MADRS \<50% were to receive 120 mg for remaining 4 weeks of treatment (up-titration from 60 mg to 120 mg for those randomized to 60 mg, and addition of placebo to 120 mg dose for those randomized to 120 mg). However, 2/70 patients randomized to 60 mg and then up-titrated to 120 mg after 4 weeks had reduction in MADRS ≥50% after 4 weeks, and 3/64 patients randomized to 120 mg and then given placebo in addition after 4 weeks had reduction in MADRS ≥50% after 4 weeks. |
| Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Baseline to Weeks 1, 2, 3, 4, 6, 8 | The HAMD-6 (Items 1,2,7,8,10,13 from the 17-item HAMD) evaluates core symptoms of Major Depressive Disorder (MDD). Total scores range from 0 (normal) to 22 (severe). |
| Reason for Living (RFL) Questionnaire Mean Scores at Baseline and Week 8 | Baseline and Week 8 | The RFL questionnaire is an instrument that evaluates patient's reasons for not committing suicide using a 6-point rating scale, where 1 is not at all important and 6 is extremely important. The questionnaire required participants to rate how important each item would be for living, if suicide was contemplated. Mean scores could range from 0 to 6. |
| Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication | over 8 weeks | Number of participants using medication for anxiety and sleep disturbances. |
| Number of Patients With Potentially Clinically Significant Laboratory Findings | over 8 weeks | Laboratory results that were potentially clinically significant. |
| Discontinuations Due to Adverse Events (AE) | over 8 weeks | Listing of adverse events (AE) that led to treatment discontinuation (DC). |
| Number of Participants Experiencing High Values for Vital Signs at Any Time During the Study | over 8 weeks | Systolic and diastolic blood pressure and pulse rate were measured after 2 minutes rest in a supine position. High values were: diastolic blood pressure ≥90 mm Hg and increase from baseline of ≥10 mm Hg; systolic blood pressure ≥140 mm Hg and increase from baseline of ≥10 mm Hg; pulse rate ≥100 beats per minute (bpm) and an increase of ≥10 bpm from baseline. |
| Change From Baseline to Week 4 and Week 8 in Weight | Baseline to Weeks 4 and 8 | Change in weight = Post-baseline visit minus baseline. |
| Patients Reaching Remission | Week 8 | Major Depressive Disorder remission was defined as a total MADRS score ≤12 at Week 8. |
Countries
France, Italy, Russia, South Africa
Participant flow
Pre-assignment details
Of the 392 patients who signed informed consent, 339 were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Duloxetine (60 mg) 60mg every day (QD) for 4 weeks, then responders continued on same dose and nonresponders increased to 60mg twice a day (BID) for next 4 weeks | 167 |
| Duloxetine (120 mg) 60mg BID for 8 weeks (placebo added at Week 4 for nonresponders) | 171 |
| Total | 338 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 11 | 9 |
| Overall Study | Didn't Receive Treatment | 0 | 1 |
| Overall Study | Lack of Efficacy | 4 | 10 |
| Overall Study | Lost to Follow-up | 1 | 2 |
| Overall Study | Non-Compliant with Protocol | 1 | 1 |
| Overall Study | Other | 0 | 1 |
| Overall Study | Withdrawal by Subject | 7 | 6 |
Baseline characteristics
| Characteristic | Total | Duloxetine (120 mg) | Duloxetine (60 mg) |
|---|---|---|---|
| Age at First Major Depressive Episode | 36.0 years STANDARD_DEVIATION 12.8 | 35.6 years STANDARD_DEVIATION 12.4 | 36.3 years STANDARD_DEVIATION 13.3 |
| Age Continuous | 44.8 years STANDARD_DEVIATION 13.3 | 43.9 years STANDARD_DEVIATION 12.7 | 45.7 years STANDARD_DEVIATION 13.9 |
| Blood Pressure Diastolic Blood Pressure | 74.7 mm Hg STANDARD_DEVIATION 8.3 | 74.7 mm Hg STANDARD_DEVIATION 8.2 | 74.6 mm Hg STANDARD_DEVIATION 8.5 |
| Blood Pressure Systolic Blood Pressure | 119.1 mm Hg STANDARD_DEVIATION 13.7 | 119.4 mm Hg STANDARD_DEVIATION 14.8 | 118.7 mm Hg STANDARD_DEVIATION 12.4 |
| Body Mass Index (BMI) | 25.3 kilograms/square meter (kg/m^2) STANDARD_DEVIATION 5.5 | 25.5 kilograms/square meter (kg/m^2) STANDARD_DEVIATION 5.5 | 25.2 kilograms/square meter (kg/m^2) STANDARD_DEVIATION 5.5 |
| Duration of Previous Major Depressive Disorder (MDD) Episode | 15.0 weeks STANDARD_DEVIATION 15.6 | 13.7 weeks STANDARD_DEVIATION 11.3 | 16.4 weeks STANDARD_DEVIATION 19 |
| Height | 166.8 centimeters (cm) STANDARD_DEVIATION 7.9 | 166.5 centimeters (cm) STANDARD_DEVIATION 7.6 | 167.1 centimeters (cm) STANDARD_DEVIATION 8.1 |
| Number of Previous Hospitalizations | 1.4 number of hospitalizations STANDARD_DEVIATION 2 | 1.5 number of hospitalizations STANDARD_DEVIATION 2.3 | 1.3 number of hospitalizations STANDARD_DEVIATION 1.6 |
| Number of Previous Major Depressive Disorder (MDD) Episodes | 3.2 number of episodes STANDARD_DEVIATION 2.9 | 3.1 number of episodes STANDARD_DEVIATION 3 | 3.2 number of episodes STANDARD_DEVIATION 2.7 |
| Previous Major Depressive Disorder Episodes No | 44 participants | 21 participants | 23 participants |
| Previous Major Depressive Disorder Episodes Yes | 294 participants | 150 participants | 144 participants |
| Pulse Rate | 75.9 beats per minute STANDARD_DEVIATION 9 | 75.8 beats per minute STANDARD_DEVIATION 9.2 | 76.0 beats per minute STANDARD_DEVIATION 8.8 |
| Race/Ethnicity Asian | 2 participants | 0 participants | 2 participants |
| Race/Ethnicity Black | 12 participants | 8 participants | 4 participants |
| Race/Ethnicity Caucasian | 324 participants | 163 participants | 161 participants |
| Region of Enrollment France | 128 participants | 64 participants | 64 participants |
| Region of Enrollment Italy | 13 participants | 6 participants | 7 participants |
| Region of Enrollment Russian Federation | 165 participants | 84 participants | 81 participants |
| Region of Enrollment South Africa | 32 participants | 17 participants | 15 participants |
| Sex: Female, Male Female | 251 Participants | 133 Participants | 118 Participants |
| Sex: Female, Male Male | 87 Participants | 38 Participants | 49 Participants |
| Weight | 70.5 kilograms (kg) STANDARD_DEVIATION 15.9 | 70.6 kilograms (kg) STANDARD_DEVIATION 15.2 | 70.4 kilograms (kg) STANDARD_DEVIATION 16.7 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 95 / — | 85 / — |
| serious Total, serious adverse events | 7 / — | 6 / — |
Outcome results
Primary
Change From Baseline to 4 Week Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Measures the overall severity of depressive 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 to Week 4
Population: All randomized participants who received at least one dose of study drug; had baseline and at least one post-baseline value. Last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine (60 mg) | Change From Baseline to 4 Week Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Baseline | 36.1 units on a scale | Standard Deviation 4 |
| Duloxetine (60 mg) | Change From Baseline to 4 Week Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Change from Baseline | -20.1 units on a scale | Standard Deviation 10.6 |
| Duloxetine (120 mg) | Change From Baseline to 4 Week Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Baseline | 36.0 units on a scale | Standard Deviation 4.6 |
| Duloxetine (120 mg) | Change From Baseline to 4 Week Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | Change from Baseline | -19.9 units on a scale | Standard Deviation 10 |
p-value: 0.88ANCOVA
Secondary
Change From Baseline to Week 4 and Week 8 in Weight
Change in weight = Post-baseline visit minus baseline.
Time frame: Baseline to Weeks 4 and 8
Population: All randomized participants with at least one dose of study drug and a baseline and at least one post-baseline value. Last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine (60 mg) | Change From Baseline to Week 4 and Week 8 in Weight | Change from Baseline to Week 4 (n=163,n=167) | 0.1 kilograms | Standard Deviation 2 |
| Duloxetine (60 mg) | Change From Baseline to Week 4 and Week 8 in Weight | Change from Baseline to Week 8 (n=163, n=168) | 0.5 kilograms | Standard Deviation 2.9 |
| Duloxetine (120 mg) | Change From Baseline to Week 4 and Week 8 in Weight | Change from Baseline to Week 4 (n=163,n=167) | 0.0 kilograms | Standard Deviation 2.3 |
| Duloxetine (120 mg) | Change From Baseline to Week 4 and Week 8 in Weight | Change from Baseline to Week 8 (n=163, n=168) | 0.1 kilograms | Standard Deviation 2.8 |
Secondary
Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline
The HAMD-6 (Items 1,2,7,8,10,13 from the 17-item HAMD) evaluates core symptoms of Major Depressive Disorder (MDD). Total scores range from 0 (normal) to 22 (severe).
Time frame: Baseline to Weeks 1, 2, 3, 4, 6, 8
Population: All randomized participants who received at least one dose of study drug and had baseline and at least one post-baseline value. Last observation carried forward. Participants were assigned their responder status at Week 4 and the data were retrospectively divided into these groups.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine (60 mg) | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 1 | -3.9 units on a scale | Standard Deviation 3.7 |
| Duloxetine (60 mg) | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 2 | -7.5 units on a scale | Standard Deviation 4.4 |
| Duloxetine (60 mg) | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 3 | -9.4 units on a scale | Standard Deviation 3.7 |
| Duloxetine (60 mg) | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 4 | -11.0 units on a scale | Standard Deviation 3.2 |
| Duloxetine (60 mg) | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 6 | -11.6 units on a scale | Standard Deviation 3.5 |
| Duloxetine (60 mg) | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 8 | -12.3 units on a scale | Standard Deviation 3.4 |
| Duloxetine (120 mg) | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 2 | -3.4 units on a scale | Standard Deviation 3.6 |
| Duloxetine (120 mg) | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 4 | -3.9 units on a scale | Standard Deviation 3.3 |
| Duloxetine (120 mg) | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 8 | -7.6 units on a scale | Standard Deviation 5.1 |
| Duloxetine (120 mg) | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 1 | -1.9 units on a scale | Standard Deviation 3.2 |
| Duloxetine (120 mg) | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 3 | -4.1 units on a scale | Standard Deviation 3.4 |
| Duloxetine (120 mg) | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 6 | -6.4 units on a scale | Standard Deviation 4.4 |
| Duloxetine 120 mg Responder | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 8 | -12.5 units on a scale | Standard Deviation 3 |
| Duloxetine 120 mg Responder | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 6 | -11.8 units on a scale | Standard Deviation 3.3 |
| Duloxetine 120 mg Responder | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 4 | -10.7 units on a scale | Standard Deviation 3 |
| Duloxetine 120 mg Responder | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 3 | -8.7 units on a scale | Standard Deviation 3.6 |
| Duloxetine 120 mg Responder | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 1 | -3.3 units on a scale | Standard Deviation 3.4 |
| Duloxetine 120 mg Responder | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 2 | -6.5 units on a scale | Standard Deviation 4.2 |
| Duloxetine 120 mg Non-Responder | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 4 | -3.8 units on a scale | Standard Deviation 3.6 |
| Duloxetine 120 mg Non-Responder | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 2 | -3.0 units on a scale | Standard Deviation 3.1 |
| Duloxetine 120 mg Non-Responder | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 3 | -3.6 units on a scale | Standard Deviation 3.7 |
| Duloxetine 120 mg Non-Responder | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 8 | -6.7 units on a scale | Standard Deviation 5.4 |
| Duloxetine 120 mg Non-Responder | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 6 | -5.5 units on a scale | Standard Deviation 4.4 |
| Duloxetine 120 mg Non-Responder | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 1 | -1.7 units on a scale | Standard Deviation 2.7 |
| Duloxetine 60 mg (All) | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 1 | -3.1 units on a scale | Standard Deviation 3.6 |
| Duloxetine 60 mg (All) | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 6 | -9.4 units on a scale | Standard Deviation 4.7 |
| Duloxetine 60 mg (All) | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 2 | -5.8 units on a scale | Standard Deviation 4.6 |
| Duloxetine 60 mg (All) | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 3 | -7.2 units on a scale | Standard Deviation 4.4 |
| Duloxetine 60 mg (All) | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 4 | -8.0 units on a scale | Standard Deviation 4.8 |
| Duloxetine 60 mg (All) | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 8 | -10.3 units on a scale | Standard Deviation 4.8 |
| Duloxetine 120 mg (All) | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 4 | -8.1 units on a scale | Standard Deviation 4.7 |
| Duloxetine 120 mg (All) | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 3 | -6.8 units on a scale | Standard Deviation 4.4 |
| Duloxetine 120 mg (All) | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 6 | -9.4 units on a scale | Standard Deviation 4.8 |
| Duloxetine 120 mg (All) | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 8 | -10.3 units on a scale | Standard Deviation 4.9 |
| Duloxetine 120 mg (All) | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 2 | -5.2 units on a scale | Standard Deviation 4.2 |
| Duloxetine 120 mg (All) | Change in 6-Item Hamilton Depression Scale (HAMD-6) Total Scores From Baseline | Change in Score at Week 1 | -2.7 units on a scale | Standard Deviation 3.3 |
Secondary
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline
Measures the overall severity of depressive 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 to Weeks 1, 2, 3, 4, 6, 8
Population: All randomized participants who received at least one dose of study drug and had baseline and at least one post-baseline value. Last observation carried forward. Participants were assigned their responder status at Week 4 and the data were retrospectively divided into these groups.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine (60 mg) | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 1 | -10.3 units on a scale | Standard Deviation 8.6 |
| Duloxetine (60 mg) | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 2 | -18.7 units on a scale | Standard Deviation 9.9 |
| Duloxetine (60 mg) | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 3 | -23.2 units on a scale | Standard Deviation 8.4 |
| Duloxetine (60 mg) | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 4 | -27.2 units on a scale | Standard Deviation 6.5 |
| Duloxetine (60 mg) | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 6 | -28.3 units on a scale | Standard Deviation 7.9 |
| Duloxetine (60 mg) | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 8 | -29.8 units on a scale | Standard Deviation 7.3 |
| Duloxetine (120 mg) | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 2 | -9.4 units on a scale | Standard Deviation 7.1 |
| Duloxetine (120 mg) | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 4 | -10.4 units on a scale | Standard Deviation 6.9 |
| Duloxetine (120 mg) | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 8 | -19.0 units on a scale | Standard Deviation 11.8 |
| Duloxetine (120 mg) | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 1 | -5.6 units on a scale | Standard Deviation 6.2 |
| Duloxetine (120 mg) | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 3 | -11.1 units on a scale | Standard Deviation 6.8 |
| Duloxetine (120 mg) | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 6 | -16.1 units on a scale | Standard Deviation 9.4 |
| Duloxetine 120 mg Responder | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 8 | -29.5 units on a scale | Standard Deviation 6.6 |
| Duloxetine 120 mg Responder | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 6 | -28.1 units on a scale | Standard Deviation 6.6 |
| Duloxetine 120 mg Responder | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 4 | -25.5 units on a scale | Standard Deviation 5.6 |
| Duloxetine 120 mg Responder | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 3 | -20.9 units on a scale | Standard Deviation 6.9 |
| Duloxetine 120 mg Responder | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 1 | -8.8 units on a scale | Standard Deviation 7.6 |
| Duloxetine 120 mg Responder | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 2 | -16.3 units on a scale | Standard Deviation 8.4 |
| Duloxetine 120 mg Non-Responder | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 4 | -10.5 units on a scale | Standard Deviation 8.6 |
| Duloxetine 120 mg Non-Responder | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 2 | -8.9 units on a scale | Standard Deviation 7.7 |
| Duloxetine 120 mg Non-Responder | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 3 | -10.3 units on a scale | Standard Deviation 9.1 |
| Duloxetine 120 mg Non-Responder | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 8 | -17.2 units on a scale | Standard Deviation 12.3 |
| Duloxetine 120 mg Non-Responder | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 6 | -14.8 units on a scale | Standard Deviation 10.4 |
| Duloxetine 120 mg Non-Responder | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 1 | -5.6 units on a scale | Standard Deviation 6.3 |
| Duloxetine 60 mg (All) | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 1 | -8.3 units on a scale | Standard Deviation 8 |
| Duloxetine 60 mg (All) | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 6 | -23.1 units on a scale | Standard Deviation 10.4 |
| Duloxetine 60 mg (All) | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 2 | -14.7 units on a scale | Standard Deviation 9.9 |
| Duloxetine 60 mg (All) | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 3 | -18.1 units on a scale | Standard Deviation 9.8 |
| Duloxetine 60 mg (All) | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 4 | -20.1 units on a scale | Standard Deviation 10.6 |
| Duloxetine 60 mg (All) | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 8 | -25.2 units on a scale | Standard Deviation 10.8 |
| Duloxetine 120 mg (All) | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 4 | -19.9 units on a scale | Standard Deviation 10 |
| Duloxetine 120 mg (All) | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 3 | -16.9 units on a scale | Standard Deviation 9.3 |
| Duloxetine 120 mg (All) | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 6 | -23.1 units on a scale | Standard Deviation 10.5 |
| Duloxetine 120 mg (All) | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 8 | -24.9 units on a scale | Standard Deviation 10.9 |
| Duloxetine 120 mg (All) | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 2 | -13.5 units on a scale | Standard Deviation 8.9 |
| Duloxetine 120 mg (All) | Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score From Baseline | Change in Score at Week 1 | -7.6 units on a scale | Standard Deviation 7.3 |
Secondary
Clinical Global Impression of Improvement (CGI-I) at Each Visit
Measures clinician's perception of patient improvement at the time of assessment compared with the start of treatment. Scores range from 1 (very much better) to 7 (very much worse).
Time frame: Weeks 1, 2, 3, 4, 6, 8
Population: All randomized participants who received at least one dose of study drug; had baseline and at least one post-baseline value. Last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine (60 mg) | Clinical Global Impression of Improvement (CGI-I) at Each Visit | Week 1 | 3.1 units on a scale | Standard Deviation 0.8 |
| Duloxetine (60 mg) | Clinical Global Impression of Improvement (CGI-I) at Each Visit | Week 2 | 2.5 units on a scale | Standard Deviation 1 |
| Duloxetine (60 mg) | Clinical Global Impression of Improvement (CGI-I) at Each Visit | Week 3 | 2.3 units on a scale | Standard Deviation 0.9 |
| Duloxetine (60 mg) | Clinical Global Impression of Improvement (CGI-I) at Each Visit | Week 4 | 2.3 units on a scale | Standard Deviation 1.1 |
| Duloxetine (60 mg) | Clinical Global Impression of Improvement (CGI-I) at Each Visit | Week 6 | 2.0 units on a scale | Standard Deviation 1.1 |
| Duloxetine (60 mg) | Clinical Global Impression of Improvement (CGI-I) at Each Visit | Week 8 | 1.9 units on a scale | Standard Deviation 1.2 |
| Duloxetine (120 mg) | Clinical Global Impression of Improvement (CGI-I) at Each Visit | Week 6 | 2.0 units on a scale | Standard Deviation 1.1 |
| Duloxetine (120 mg) | Clinical Global Impression of Improvement (CGI-I) at Each Visit | Week 1 | 3.2 units on a scale | Standard Deviation 0.8 |
| Duloxetine (120 mg) | Clinical Global Impression of Improvement (CGI-I) at Each Visit | Week 4 | 2.1 units on a scale | Standard Deviation 1 |
| Duloxetine (120 mg) | Clinical Global Impression of Improvement (CGI-I) at Each Visit | Week 2 | 2.6 units on a scale | Standard Deviation 0.8 |
| Duloxetine (120 mg) | Clinical Global Impression of Improvement (CGI-I) at Each Visit | Week 8 | 1.9 units on a scale | Standard Deviation 1.1 |
| Duloxetine (120 mg) | Clinical Global Impression of Improvement (CGI-I) at Each Visit | Week 3 | 2.3 units on a scale | Standard Deviation 0.9 |
Secondary
Clinical Global Impression of Severity (CGI-S) Scores at Each Visit
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).
Time frame: Baseline, Weeks 1, 2, 3, 4, 6, 8
Population: All randomized participants who received at least one dose of study drug; had baseline and at least one post-baseline value. Last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine (60 mg) | Clinical Global Impression of Severity (CGI-S) Scores at Each Visit | Week 2 | 3.6 units on a scale | Standard Deviation 1.2 |
| Duloxetine (60 mg) | Clinical Global Impression of Severity (CGI-S) Scores at Each Visit | Week 4 | 3.0 units on a scale | Standard Deviation 1.4 |
| Duloxetine (60 mg) | Clinical Global Impression of Severity (CGI-S) Scores at Each Visit | Week 1 | 4.4 units on a scale | Standard Deviation 0.9 |
| Duloxetine (60 mg) | Clinical Global Impression of Severity (CGI-S) Scores at Each Visit | Week 6 | 2.7 units on a scale | Standard Deviation 1.4 |
| Duloxetine (60 mg) | Clinical Global Impression of Severity (CGI-S) Scores at Each Visit | Week 3 | 3.2 units on a scale | Standard Deviation 1.3 |
| Duloxetine (60 mg) | Clinical Global Impression of Severity (CGI-S) Scores at Each Visit | Week 8 | 2.3 units on a scale | Standard Deviation 1.4 |
| Duloxetine (60 mg) | Clinical Global Impression of Severity (CGI-S) Scores at Each Visit | Week 0 (Baseline) | 5.0 units on a scale | Standard Deviation 0.7 |
| Duloxetine (120 mg) | Clinical Global Impression of Severity (CGI-S) Scores at Each Visit | Week 8 | 2.4 units on a scale | Standard Deviation 1.5 |
| Duloxetine (120 mg) | Clinical Global Impression of Severity (CGI-S) Scores at Each Visit | Week 0 (Baseline) | 5.1 units on a scale | Standard Deviation 0.7 |
| Duloxetine (120 mg) | Clinical Global Impression of Severity (CGI-S) Scores at Each Visit | Week 1 | 4.4 units on a scale | Standard Deviation 0.9 |
| Duloxetine (120 mg) | Clinical Global Impression of Severity (CGI-S) Scores at Each Visit | Week 2 | 3.8 units on a scale | Standard Deviation 1.1 |
| Duloxetine (120 mg) | Clinical Global Impression of Severity (CGI-S) Scores at Each Visit | Week 3 | 3.4 units on a scale | Standard Deviation 1.2 |
| Duloxetine (120 mg) | Clinical Global Impression of Severity (CGI-S) Scores at Each Visit | Week 4 | 3.1 units on a scale | Standard Deviation 1.3 |
| Duloxetine (120 mg) | Clinical Global Impression of Severity (CGI-S) Scores at Each Visit | Week 6 | 2.7 units on a scale | Standard Deviation 1.4 |
Secondary
Discontinuations Due to Adverse Events (AE)
Listing of adverse events (AE) that led to treatment discontinuation (DC).
Time frame: over 8 weeks
Population: All randomized participants with at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine (60 mg) | Discontinuations Due to Adverse Events (AE) | Nausea | 1 participants |
| Duloxetine (60 mg) | Discontinuations Due to Adverse Events (AE) | Suicidal Ideation | 2 participants |
| Duloxetine (60 mg) | Discontinuations Due to Adverse Events (AE) | Irritability | 1 participants |
| Duloxetine (60 mg) | Discontinuations Due to Adverse Events (AE) | Major Depression | 1 participants |
| Duloxetine (60 mg) | Discontinuations Due to Adverse Events (AE) | Brain Neoplasm | 0 participants |
| Duloxetine (60 mg) | Discontinuations Due to Adverse Events (AE) | Suicide Attempt | 3 participants |
| Duloxetine (60 mg) | Discontinuations Due to Adverse Events (AE) | Dizziness | 0 participants |
| Duloxetine (60 mg) | Discontinuations Due to Adverse Events (AE) | Psychotic Disorder | 1 participants |
| Duloxetine (60 mg) | Discontinuations Due to Adverse Events (AE) | Sedation | 0 participants |
| Duloxetine (60 mg) | Discontinuations Due to Adverse Events (AE) | Schizoaffective Disorder | 1 participants |
| Duloxetine (60 mg) | Discontinuations Due to Adverse Events (AE) | Serotonin Syndrome | 0 participants |
| Duloxetine (60 mg) | Discontinuations Due to Adverse Events (AE) | Hypothyroidism | 1 participants |
| Duloxetine (60 mg) | Discontinuations Due to Adverse Events (AE) | Upper Abdominal Pain | 0 participants |
| Duloxetine (60 mg) | Discontinuations Due to Adverse Events (AE) | Self-Injurious Behaviour | 1 participants |
| Duloxetine (60 mg) | Discontinuations Due to Adverse Events (AE) | Drug Eruption | 0 participants |
| Duloxetine (60 mg) | Discontinuations Due to Adverse Events (AE) | Total Number of Patients With AEs Leading to DC | 11 participants |
| Duloxetine (60 mg) | Discontinuations Due to Adverse Events (AE) | Renal Failure | 0 participants |
| Duloxetine (60 mg) | Discontinuations Due to Adverse Events (AE) | Headache | 1 participants |
| Duloxetine (60 mg) | Discontinuations Due to Adverse Events (AE) | Urinary Retention | 0 participants |
| Duloxetine (60 mg) | Discontinuations Due to Adverse Events (AE) | Depression | 1 participants |
| Duloxetine (120 mg) | Discontinuations Due to Adverse Events (AE) | Urinary Retention | 1 participants |
| Duloxetine (120 mg) | Discontinuations Due to Adverse Events (AE) | Total Number of Patients With AEs Leading to DC | 9 participants |
| Duloxetine (120 mg) | Discontinuations Due to Adverse Events (AE) | Suicide Attempt | 0 participants |
| Duloxetine (120 mg) | Discontinuations Due to Adverse Events (AE) | Suicidal Ideation | 1 participants |
| Duloxetine (120 mg) | Discontinuations Due to Adverse Events (AE) | Hypothyroidism | 0 participants |
| Duloxetine (120 mg) | Discontinuations Due to Adverse Events (AE) | Depression | 2 participants |
| Duloxetine (120 mg) | Discontinuations Due to Adverse Events (AE) | Major Depression | 0 participants |
| Duloxetine (120 mg) | Discontinuations Due to Adverse Events (AE) | Schizoaffective Disorder | 0 participants |
| Duloxetine (120 mg) | Discontinuations Due to Adverse Events (AE) | Self-Injurious Behaviour | 0 participants |
| Duloxetine (120 mg) | Discontinuations Due to Adverse Events (AE) | Headache | 0 participants |
| Duloxetine (120 mg) | Discontinuations Due to Adverse Events (AE) | Nausea | 0 participants |
| Duloxetine (120 mg) | Discontinuations Due to Adverse Events (AE) | Irritability | 0 participants |
| Duloxetine (120 mg) | Discontinuations Due to Adverse Events (AE) | Brain Neoplasm | 1 participants |
| Duloxetine (120 mg) | Discontinuations Due to Adverse Events (AE) | Dizziness | 1 participants |
| Duloxetine (120 mg) | Discontinuations Due to Adverse Events (AE) | Sedation | 1 participants |
| Duloxetine (120 mg) | Discontinuations Due to Adverse Events (AE) | Serotonin Syndrome | 1 participants |
| Duloxetine (120 mg) | Discontinuations Due to Adverse Events (AE) | Upper Abdominal Pain | 1 participants |
| Duloxetine (120 mg) | Discontinuations Due to Adverse Events (AE) | Drug Eruption | 1 participants |
| Duloxetine (120 mg) | Discontinuations Due to Adverse Events (AE) | Renal Failure | 1 participants |
| Duloxetine (120 mg) | Discontinuations Due to Adverse Events (AE) | Psychotic Disorder | 0 participants |
Secondary
Evaluation of Rescue Options Based on Changes in the Montgomery-Asberg Depression Rating Scale (MADRS) and the 6-Item Hamilton Depression Scale (HAMD-6)
Changes in Montgomery-Åsberg Depression Rating Scale (MADRS) and 6-Item Hamilton Depression Scale (HAMD-6) total scores were evaluated following dose up-titration in those patients who did not achieve the minimum 50% response for primary endpoint. MADRS is a rating scale for severity of depressive mood symptoms. Total scores range from 0 (low severity of symptoms) to 60 (high severity of symptoms). The HAMD-6, derived by the sum of HAMD-17 items 1, 2, 7, 8, 10 and 13, evaluates core symptoms of Major Depressive Disorder (MDD). Total subscale scores range from 0 (normal) to 22 (severe).
Time frame: 4 to 8 weeks
Population: All randomized participants who received at least one dose of study drug and had a Week 4 and at least one following value. Last observation carried forward. Participants were assigned their responder status at Week 4 and the data were retrospectively divided into these groups.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine (60 mg) | Evaluation of Rescue Options Based on Changes in the Montgomery-Asberg Depression Rating Scale (MADRS) and the 6-Item Hamilton Depression Scale (HAMD-6) | Change in MADRS Score from Week 4 to Week 6 | -1.0 units on a scale | Standard Deviation 5.1 |
| Duloxetine (60 mg) | Evaluation of Rescue Options Based on Changes in the Montgomery-Asberg Depression Rating Scale (MADRS) and the 6-Item Hamilton Depression Scale (HAMD-6) | Change in MADRS Score from Week 4 to Week 8 | -2.6 units on a scale | Standard Deviation 6 |
| Duloxetine (60 mg) | Evaluation of Rescue Options Based on Changes in the Montgomery-Asberg Depression Rating Scale (MADRS) and the 6-Item Hamilton Depression Scale (HAMD-6) | Change in HAMD-6 Score from Week 4 to Week 6 | -0.6 units on a scale | Standard Deviation 2.7 |
| Duloxetine (60 mg) | Evaluation of Rescue Options Based on Changes in the Montgomery-Asberg Depression Rating Scale (MADRS) and the 6-Item Hamilton Depression Scale (HAMD-6) | Change in HMAD-6 Score from Week 4 to Week 8 | -1.3 units on a scale | Standard Deviation 2.8 |
| Duloxetine (120 mg) | Evaluation of Rescue Options Based on Changes in the Montgomery-Asberg Depression Rating Scale (MADRS) and the 6-Item Hamilton Depression Scale (HAMD-6) | Change in MADRS Score from Week 4 to Week 8 | -10.9 units on a scale | Standard Deviation 8.8 |
| Duloxetine (120 mg) | Evaluation of Rescue Options Based on Changes in the Montgomery-Asberg Depression Rating Scale (MADRS) and the 6-Item Hamilton Depression Scale (HAMD-6) | Change in HAMD-6 Score from Week 4 to Week 6 | -3.2 units on a scale | Standard Deviation 2.7 |
| Duloxetine (120 mg) | Evaluation of Rescue Options Based on Changes in the Montgomery-Asberg Depression Rating Scale (MADRS) and the 6-Item Hamilton Depression Scale (HAMD-6) | Change in HMAD-6 Score from Week 4 to Week 8 | -4.7 units on a scale | Standard Deviation 3.6 |
| Duloxetine (120 mg) | Evaluation of Rescue Options Based on Changes in the Montgomery-Asberg Depression Rating Scale (MADRS) and the 6-Item Hamilton Depression Scale (HAMD-6) | Change in MADRS Score from Week 4 to Week 6 | -7.2 units on a scale | Standard Deviation 6.3 |
| Duloxetine 120 mg Responder | Evaluation of Rescue Options Based on Changes in the Montgomery-Asberg Depression Rating Scale (MADRS) and the 6-Item Hamilton Depression Scale (HAMD-6) | Change in HAMD-6 Score from Week 4 to Week 6 | -1.1 units on a scale | Standard Deviation 1.8 |
| Duloxetine 120 mg Responder | Evaluation of Rescue Options Based on Changes in the Montgomery-Asberg Depression Rating Scale (MADRS) and the 6-Item Hamilton Depression Scale (HAMD-6) | Change in MADRS Score from Week 4 to Week 8 | -4.0 units on a scale | Standard Deviation 5.3 |
| Duloxetine 120 mg Responder | Evaluation of Rescue Options Based on Changes in the Montgomery-Asberg Depression Rating Scale (MADRS) and the 6-Item Hamilton Depression Scale (HAMD-6) | Change in HMAD-6 Score from Week 4 to Week 8 | -1.8 units on a scale | Standard Deviation 2.4 |
| Duloxetine 120 mg Responder | Evaluation of Rescue Options Based on Changes in the Montgomery-Asberg Depression Rating Scale (MADRS) and the 6-Item Hamilton Depression Scale (HAMD-6) | Change in MADRS Score from Week 4 to Week 6 | -2.6 units on a scale | Standard Deviation 4.2 |
| Duloxetine 120 mg Non-Responder | Evaluation of Rescue Options Based on Changes in the Montgomery-Asberg Depression Rating Scale (MADRS) and the 6-Item Hamilton Depression Scale (HAMD-6) | Change in HMAD-6 Score from Week 4 to Week 8 | -3.8 units on a scale | Standard Deviation 4.3 |
| Duloxetine 120 mg Non-Responder | Evaluation of Rescue Options Based on Changes in the Montgomery-Asberg Depression Rating Scale (MADRS) and the 6-Item Hamilton Depression Scale (HAMD-6) | Change in MADRS Score from Week 4 to Week 8 | -8.9 units on a scale | Standard Deviation 9.1 |
| Duloxetine 120 mg Non-Responder | Evaluation of Rescue Options Based on Changes in the Montgomery-Asberg Depression Rating Scale (MADRS) and the 6-Item Hamilton Depression Scale (HAMD-6) | Change in MADRS Score from Week 4 to Week 6 | -5.8 units on a scale | Standard Deviation 7 |
| Duloxetine 120 mg Non-Responder | Evaluation of Rescue Options Based on Changes in the Montgomery-Asberg Depression Rating Scale (MADRS) and the 6-Item Hamilton Depression Scale (HAMD-6) | Change in HAMD-6 Score from Week 4 to Week 6 | -2.2 units on a scale | Standard Deviation 3.1 |
Secondary
Hamilton Anxiety Scale (HAMA) Score at Baseline and Weeks 4 and 8
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.
Time frame: Baseline and Weeks 4 and 8
Population: All randomized participants who received at least one dose of study drug; had baseline and at least one post-baseline value. Last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine (60 mg) | Hamilton Anxiety Scale (HAMA) Score at Baseline and Weeks 4 and 8 | Week 0 (Baseline) (n=166, n=170) | 26.0 units on a scale | Standard Deviation 6.4 |
| Duloxetine (60 mg) | Hamilton Anxiety Scale (HAMA) Score at Baseline and Weeks 4 and 8 | Week 4 (n=165, n=168) | 13.0 units on a scale | Standard Deviation 8.8 |
| Duloxetine (60 mg) | Hamilton Anxiety Scale (HAMA) Score at Baseline and Weeks 4 and 8 | Week 8 (n=165, n=168) | 9.6 units on a scale | Standard Deviation 8.8 |
| Duloxetine (120 mg) | Hamilton Anxiety Scale (HAMA) Score at Baseline and Weeks 4 and 8 | Week 0 (Baseline) (n=166, n=170) | 27.0 units on a scale | Standard Deviation 7 |
| Duloxetine (120 mg) | Hamilton Anxiety Scale (HAMA) Score at Baseline and Weeks 4 and 8 | Week 4 (n=165, n=168) | 13.4 units on a scale | Standard Deviation 8.9 |
| Duloxetine (120 mg) | Hamilton Anxiety Scale (HAMA) Score at Baseline and Weeks 4 and 8 | Week 8 (n=165, n=168) | 9.8 units on a scale | Standard Deviation 9.2 |
Secondary
Number of Participants Experiencing High Values for Vital Signs at Any Time During the Study
Systolic and diastolic blood pressure and pulse rate were measured after 2 minutes rest in a supine position. High values were: diastolic blood pressure ≥90 mm Hg and increase from baseline of ≥10 mm Hg; systolic blood pressure ≥140 mm Hg and increase from baseline of ≥10 mm Hg; pulse rate ≥100 beats per minute (bpm) and an increase of ≥10 bpm from baseline.
Time frame: over 8 weeks
Population: All randomized participants with at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine (60 mg) | Number of Participants Experiencing High Values for Vital Signs at Any Time During the Study | High Systolic Blood Pressure | 23 participants |
| Duloxetine (60 mg) | Number of Participants Experiencing High Values for Vital Signs at Any Time During the Study | High Diastolic Blood Pressure | 28 participants |
| Duloxetine (60 mg) | Number of Participants Experiencing High Values for Vital Signs at Any Time During the Study | High Pulse Rate | 10 participants |
| Duloxetine (120 mg) | Number of Participants Experiencing High Values for Vital Signs at Any Time During the Study | High Systolic Blood Pressure | 25 participants |
| Duloxetine (120 mg) | Number of Participants Experiencing High Values for Vital Signs at Any Time During the Study | High Diastolic Blood Pressure | 37 participants |
| Duloxetine (120 mg) | Number of Participants Experiencing High Values for Vital Signs at Any Time During the Study | High Pulse Rate | 14 participants |
Secondary
Number of Patients With Potentially Clinically Significant Laboratory Findings
Laboratory results that were potentially clinically significant.
Time frame: over 8 weeks
Population: All randomized participants with at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine (60 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Decreased Haemoglobin (n=156, n=160) | 2 participants |
| Duloxetine (60 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Increased Alkaline Phosphatase (n=161, n=163) | 0 participants |
| Duloxetine (60 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Decreased Sodium (n=160, n=163) | 1 participants |
| Duloxetine (60 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Increased Gamma-Glutamyl Transferase (n=161,n=163) | 2 participants |
| Duloxetine (60 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Increased Mean Cell Volume (n=155, n=159) | 0 participants |
| Duloxetine (60 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Increased Creatine Kinase (n=159, n=161) | 6 participants |
| Duloxetine (60 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Increased Potassium (n=159, n=163) | 0 participants |
| Duloxetine (60 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Decreased Glucose (n=158, n=162) | 1 participants |
| Duloxetine (60 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Decreased Red Cell Count (n=156, n=160) | 0 participants |
| Duloxetine (60 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Increased Cholesterol (n=160, n=163) | 1 participants |
| Duloxetine (60 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Increased Aspartate Transaminase (n=158, n=161) | 2 participants |
| Duloxetine (60 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Increased Total Bilirubin (n=159, n=161) | 0 participants |
| Duloxetine (60 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Decreased White Cell Count (n=156, n=160) | 1 participants |
| Duloxetine (60 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Increased Uric Acid (n=160, n=163) | 0 participants |
| Duloxetine (60 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Increased Alanine Transaminase (n=159, n=161) | 3 participants |
| Duloxetine (60 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Decreased Albumin (n=158, n=161) | 0 participants |
| Duloxetine (60 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Decreased Haematocrit (n=155, n=159) | 0 participants |
| Duloxetine (120 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Decreased Albumin (n=158, n=161) | 1 participants |
| Duloxetine (120 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Decreased Haematocrit (n=155, n=159) | 1 participants |
| Duloxetine (120 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Decreased Haemoglobin (n=156, n=160) | 2 participants |
| Duloxetine (120 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Decreased Red Cell Count (n=156, n=160) | 1 participants |
| Duloxetine (120 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Increased Mean Cell Volume (n=155, n=159) | 1 participants |
| Duloxetine (120 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Decreased White Cell Count (n=156, n=160) | 2 participants |
| Duloxetine (120 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Decreased Sodium (n=160, n=163) | 0 participants |
| Duloxetine (120 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Increased Potassium (n=159, n=163) | 1 participants |
| Duloxetine (120 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Increased Aspartate Transaminase (n=158, n=161) | 0 participants |
| Duloxetine (120 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Increased Alanine Transaminase (n=159, n=161) | 1 participants |
| Duloxetine (120 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Increased Alkaline Phosphatase (n=161, n=163) | 1 participants |
| Duloxetine (120 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Increased Gamma-Glutamyl Transferase (n=161,n=163) | 0 participants |
| Duloxetine (120 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Increased Creatine Kinase (n=159, n=161) | 3 participants |
| Duloxetine (120 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Decreased Glucose (n=158, n=162) | 1 participants |
| Duloxetine (120 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Increased Cholesterol (n=160, n=163) | 0 participants |
| Duloxetine (120 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Increased Total Bilirubin (n=159, n=161) | 1 participants |
| Duloxetine (120 mg) | Number of Patients With Potentially Clinically Significant Laboratory Findings | Increased Uric Acid (n=160, n=163) | 2 participants |
Secondary
Patient Global Impression of Improvement (PGI-I) Score at Each Visit
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).
Time frame: Weeks 1, 2, 3, 4, 6, 8
Population: All randomized participants who received at least one dose of study drug; had baseline and at least one post-baseline value. Last observation carried forward.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine (60 mg) | Patient Global Impression of Improvement (PGI-I) Score at Each Visit | Week 2 (n=164, n=170) | 2.6 units on a scale | Standard Deviation 1.1 |
| Duloxetine (60 mg) | Patient Global Impression of Improvement (PGI-I) Score at Each Visit | Week 4 (n=165, n=170) | 2.3 units on a scale | Standard Deviation 1.2 |
| Duloxetine (60 mg) | Patient Global Impression of Improvement (PGI-I) Score at Each Visit | Week 1 (n=164, n=170) | 3.0 units on a scale | Standard Deviation 1 |
| Duloxetine (60 mg) | Patient Global Impression of Improvement (PGI-I) Score at Each Visit | Week 6 (n=165, n=170) | 2.1 units on a scale | Standard Deviation 1.3 |
| Duloxetine (60 mg) | Patient Global Impression of Improvement (PGI-I) Score at Each Visit | Week 8 (n=165, n=170) | 2.0 units on a scale | Standard Deviation 1.3 |
| Duloxetine (60 mg) | Patient Global Impression of Improvement (PGI-I) Score at Each Visit | Week 3 (n=165, n=170) | 2.3 units on a scale | Standard Deviation 1.1 |
| Duloxetine (120 mg) | Patient Global Impression of Improvement (PGI-I) Score at Each Visit | Week 8 (n=165, n=170) | 1.9 units on a scale | Standard Deviation 1.2 |
| Duloxetine (120 mg) | Patient Global Impression of Improvement (PGI-I) Score at Each Visit | Week 1 (n=164, n=170) | 3.1 units on a scale | Standard Deviation 0.9 |
| Duloxetine (120 mg) | Patient Global Impression of Improvement (PGI-I) Score at Each Visit | Week 2 (n=164, n=170) | 2.6 units on a scale | Standard Deviation 0.9 |
| Duloxetine (120 mg) | Patient Global Impression of Improvement (PGI-I) Score at Each Visit | Week 3 (n=165, n=170) | 2.4 units on a scale | Standard Deviation 1.1 |
| Duloxetine (120 mg) | Patient Global Impression of Improvement (PGI-I) Score at Each Visit | Week 4 (n=165, n=170) | 2.2 units on a scale | Standard Deviation 1.2 |
| Duloxetine (120 mg) | Patient Global Impression of Improvement (PGI-I) Score at Each Visit | Week 6 (n=165, n=170) | 2.0 units on a scale | Standard Deviation 1.1 |
Secondary
Patients Reaching Remission
Major Depressive Disorder remission was defined as a total MADRS score ≤12 at Week 8.
Time frame: Week 8
Population: All randomized participants who received at least one dose of study drug and had baseline and at least one post-baseline value. Last observation carried forward. Participants were assigned their responder status at Week 4 and the data were retrospectively divided into these groups.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine (60 mg) | Patients Reaching Remission | Remission at Week 8 - Yes | 85 participants |
| Duloxetine (60 mg) | Patients Reaching Remission | Remission at Week 8 - No | 11 participants |
| Duloxetine (120 mg) | Patients Reaching Remission | Remission at Week 8 - No | 41 participants |
| Duloxetine (120 mg) | Patients Reaching Remission | Remission at Week 8 - Yes | 29 participants |
| Duloxetine 120 mg Responder | Patients Reaching Remission | Remission at Week 8 - Yes | 94 participants |
| Duloxetine 120 mg Responder | Patients Reaching Remission | Remission at Week 8 - No | 12 participants |
| Duloxetine 120 mg Non-Responder | Patients Reaching Remission | Remission at Week 8 - Yes | 18 participants |
| Duloxetine 120 mg Non-Responder | Patients Reaching Remission | Remission at Week 8 - No | 46 participants |
Secondary
Percentage of Responders
Patients with reduction in MADRS score ≥50% after 4 weeks were to stay on previous dose of duloxetine. Those with reduction in MADRS \<50% were to receive 120 mg for remaining 4 weeks of treatment (up-titration from 60 mg to 120 mg for those randomized to 60 mg, and addition of placebo to 120 mg dose for those randomized to 120 mg). However, 2/70 patients randomized to 60 mg and then up-titrated to 120 mg after 4 weeks had reduction in MADRS ≥50% after 4 weeks, and 3/64 patients randomized to 120 mg and then given placebo in addition after 4 weeks had reduction in MADRS ≥50% after 4 weeks.
Time frame: 4 to 8 weeks
Population: All randomized participants who received at least one dose of study drug and had baseline and at least one post-baseline value. Last observation carried forward. Participants were assigned their responder status at Week 4 and the data were retrospectively divided into these groups.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine (60 mg) | Percentage of Responders | ≥50% Reduction in HAMD-6 Week 6 | 90.6 percentage of participants |
| Duloxetine (60 mg) | Percentage of Responders | ≥50% Reduction in MADRS Week 6 | 94.8 percentage of participants |
| Duloxetine (60 mg) | Percentage of Responders | ≥50% Reduction in HAMD-6 Week 8 | 92.7 percentage of participants |
| Duloxetine (60 mg) | Percentage of Responders | ≥50% Reduction in MADRS Week 8 | 93.8 percentage of participants |
| Duloxetine (60 mg) | Percentage of Responders | ≥50% Reduction in HAMD-6 Week 4 | 88.5 percentage of participants |
| Duloxetine (60 mg) | Percentage of Responders | ≥50% Reduction in MADRS Week 4 | 100.0 percentage of participants |
| Duloxetine (120 mg) | Percentage of Responders | ≥50% Reduction in MADRS Week 8 | 65.7 percentage of participants |
| Duloxetine (120 mg) | Percentage of Responders | ≥50% Reduction in HAMD-6 Week 6 | 47.1 percentage of participants |
| Duloxetine (120 mg) | Percentage of Responders | ≥50% Reduction in HAMD-6 Week 4 | 10.0 percentage of participants |
| Duloxetine (120 mg) | Percentage of Responders | ≥50% Reduction in HAMD-6 Week 8 | 60.0 percentage of participants |
| Duloxetine (120 mg) | Percentage of Responders | ≥50% Reduction in MADRS Week 4 | 2.9 percentage of participants |
| Duloxetine (120 mg) | Percentage of Responders | ≥50% Reduction in MADRS Week 6 | 52.9 percentage of participants |
| Duloxetine 120 mg Responder | Percentage of Responders | ≥50% Reduction in HAMD-6 Week 6 | 90.6 percentage of participants |
| Duloxetine 120 mg Responder | Percentage of Responders | ≥50% Reduction in MADRS Week 6 | 98.1 percentage of participants |
| Duloxetine 120 mg Responder | Percentage of Responders | ≥50% Reduction in HAMD-6 Week 4 | 85.8 percentage of participants |
| Duloxetine 120 mg Responder | Percentage of Responders | ≥50% Reduction in MADRS Week 8 | 98.1 percentage of participants |
| Duloxetine 120 mg Responder | Percentage of Responders | ≥50% Reduction in MADRS Week 4 | 100.0 percentage of participants |
| Duloxetine 120 mg Responder | Percentage of Responders | ≥50% Reduction in HAMD-6 Week 8 | 95.3 percentage of participants |
| Duloxetine 120 mg Non-Responder | Percentage of Responders | ≥50% Reduction in HAMD-6 Week 8 | 46.9 percentage of participants |
| Duloxetine 120 mg Non-Responder | Percentage of Responders | ≥50% Reduction in MADRS Week 4 | 4.7 percentage of participants |
| Duloxetine 120 mg Non-Responder | Percentage of Responders | ≥50% Reduction in MADRS Week 6 | 39.1 percentage of participants |
| Duloxetine 120 mg Non-Responder | Percentage of Responders | ≥50% Reduction in MADRS Week 8 | 54.7 percentage of participants |
| Duloxetine 120 mg Non-Responder | Percentage of Responders | ≥50% Reduction in HAMD-6 Week 4 | 12.5 percentage of participants |
| Duloxetine 120 mg Non-Responder | Percentage of Responders | ≥50% Reduction in HAMD-6 Week 6 | 31.3 percentage of participants |
Secondary
Reason for Living (RFL) Questionnaire Mean Scores at Baseline and Week 8
The RFL questionnaire is an instrument that evaluates patient's reasons for not committing suicide using a 6-point rating scale, where 1 is not at all important and 6 is extremely important. The questionnaire required participants to rate how important each item would be for living, if suicide was contemplated. Mean scores could range from 0 to 6.
Time frame: Baseline and Week 8
Population: All randomized participants who received at least one dose of study drug and had baseline and at least one post-baseline value. Last observation carried forward. Participants were assigned their responder status at Week 4 and the data were retrospectively divided into these groups.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Duloxetine (60 mg) | Reason for Living (RFL) Questionnaire Mean Scores at Baseline and Week 8 | Week 8 (n=93, n=63, n=100, n=59) | 4.6 units on a scale | Standard Deviation 0.9 |
| Duloxetine (60 mg) | Reason for Living (RFL) Questionnaire Mean Scores at Baseline and Week 8 | Week 0 (Baseline) (n=96, n=66, n=106, n=61) | 4.0 units on a scale | Standard Deviation 1.1 |
| Duloxetine (60 mg) | Reason for Living (RFL) Questionnaire Mean Scores at Baseline and Week 8 | Change from Baseline (n=93, n=59, n=100, n=57) | 0.7 units on a scale | Standard Deviation 0.9 |
| Duloxetine (120 mg) | Reason for Living (RFL) Questionnaire Mean Scores at Baseline and Week 8 | Week 8 (n=93, n=63, n=100, n=59) | 4.0 units on a scale | Standard Deviation 1.2 |
| Duloxetine (120 mg) | Reason for Living (RFL) Questionnaire Mean Scores at Baseline and Week 8 | Week 0 (Baseline) (n=96, n=66, n=106, n=61) | 3.6 units on a scale | Standard Deviation 1 |
| Duloxetine (120 mg) | Reason for Living (RFL) Questionnaire Mean Scores at Baseline and Week 8 | Change from Baseline (n=93, n=59, n=100, n=57) | 0.4 units on a scale | Standard Deviation 0.8 |
| Duloxetine 120 mg Responder | Reason for Living (RFL) Questionnaire Mean Scores at Baseline and Week 8 | Week 8 (n=93, n=63, n=100, n=59) | 4.6 units on a scale | Standard Deviation 0.9 |
| Duloxetine 120 mg Responder | Reason for Living (RFL) Questionnaire Mean Scores at Baseline and Week 8 | Week 0 (Baseline) (n=96, n=66, n=106, n=61) | 3.7 units on a scale | Standard Deviation 1 |
| Duloxetine 120 mg Responder | Reason for Living (RFL) Questionnaire Mean Scores at Baseline and Week 8 | Change from Baseline (n=93, n=59, n=100, n=57) | 0.8 units on a scale | Standard Deviation 0.8 |
| Duloxetine 120 mg Non-Responder | Reason for Living (RFL) Questionnaire Mean Scores at Baseline and Week 8 | Week 8 (n=93, n=63, n=100, n=59) | 3.8 units on a scale | Standard Deviation 1.1 |
| Duloxetine 120 mg Non-Responder | Reason for Living (RFL) Questionnaire Mean Scores at Baseline and Week 8 | Week 0 (Baseline) (n=96, n=66, n=106, n=61) | 3.7 units on a scale | Standard Deviation 1 |
| Duloxetine 120 mg Non-Responder | Reason for Living (RFL) Questionnaire Mean Scores at Baseline and Week 8 | Change from Baseline (n=93, n=59, n=100, n=57) | 0.1 units on a scale | Standard Deviation 0.9 |
| Duloxetine 60 mg (All) | Reason for Living (RFL) Questionnaire Mean Scores at Baseline and Week 8 | Week 8 (n=93, n=63, n=100, n=59) | 4.4 units on a scale | Standard Deviation 1.1 |
| Duloxetine 60 mg (All) | Reason for Living (RFL) Questionnaire Mean Scores at Baseline and Week 8 | Week 0 (Baseline) (n=96, n=66, n=106, n=61) | 3.8 units on a scale | Standard Deviation 1.1 |
| Duloxetine 60 mg (All) | Reason for Living (RFL) Questionnaire Mean Scores at Baseline and Week 8 | Change from Baseline (n=93, n=59, n=100, n=57) | 0.6 units on a scale | Standard Deviation 0.9 |
| Duloxetine 120 mg (All) | Reason for Living (RFL) Questionnaire Mean Scores at Baseline and Week 8 | Week 0 (Baseline) (n=96, n=66, n=106, n=61) | 3.7 units on a scale | Standard Deviation 1 |
| Duloxetine 120 mg (All) | Reason for Living (RFL) Questionnaire Mean Scores at Baseline and Week 8 | Change from Baseline (n=93, n=59, n=100, n=57) | 0.6 units on a scale | Standard Deviation 0.9 |
| Duloxetine 120 mg (All) | Reason for Living (RFL) Questionnaire Mean Scores at Baseline and Week 8 | Week 8 (n=93, n=63, n=100, n=59) | 4.3 units on a scale | Standard Deviation 1.1 |
p-value: <0.0001t-test, 2 sided
p-value: 0.001t-test, 2 sided
p-value: <0.0001t-test, 2 sided
p-value: 0.28t-test, 2 sided
Secondary
Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication
Number of participants using medication for anxiety and sleep disturbances.
Time frame: over 8 weeks
Population: All randomized participants who received at least one dose of study drug; had baseline and at least one post-baseline value. Last observation carried forward. The total number of patients with hypnotics and anxiolytics concomitant therapies was 125 (Duloxetine 60mg) and 123 (Duloxetine 120mg).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Duloxetine (60 mg) | Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication | Medication Taken Before Start of Study (Week -1) | 65 participants |
| Duloxetine (60 mg) | Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication | Medication Taken Between Week -1 and Week 0 | 93 participants |
| Duloxetine (60 mg) | Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication | Medication Taken Between Week 0 and Week 1 | 95 participants |
| Duloxetine (60 mg) | Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication | Medication Taken Between Week 1 and Week 2 | 80 participants |
| Duloxetine (60 mg) | Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication | Medication Taken Between Week 2 and Week 3 | 62 participants |
| Duloxetine (60 mg) | Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication | Medication Taken Between Week 3 and Week 4 | 55 participants |
| Duloxetine (60 mg) | Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication | Medication Taken Between Week 4 and Week 6 | 47 participants |
| Duloxetine (60 mg) | Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication | Medication Taken Between Week 6 and Week 8 | 51 participants |
| Duloxetine (60 mg) | Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication | Medication Taken After Week 8 | 18 participants |
| Duloxetine (60 mg) | Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication | Medication Not Taken Between Consecutive Visits | 8 participants |
| Duloxetine (120 mg) | Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication | Medication Taken Between Week 6 and Week 8 | 52 participants |
| Duloxetine (120 mg) | Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication | Medication Taken Before Start of Study (Week -1) | 59 participants |
| Duloxetine (120 mg) | Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication | Medication Taken Between Week 3 and Week 4 | 58 participants |
| Duloxetine (120 mg) | Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication | Medication Taken Between Week -1 and Week 0 | 88 participants |
| Duloxetine (120 mg) | Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication | Medication Not Taken Between Consecutive Visits | 8 participants |
| Duloxetine (120 mg) | Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication | Medication Taken Between Week 0 and Week 1 | 89 participants |
| Duloxetine (120 mg) | Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication | Medication Taken Between Week 4 and Week 6 | 49 participants |
| Duloxetine (120 mg) | Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication | Medication Taken Between Week 1 and Week 2 | 84 participants |
| Duloxetine (120 mg) | Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication | Medication Taken After Week 8 | 10 participants |
| Duloxetine (120 mg) | Utilization of Allowed Hypnotic and/or Anxiolytic Co-Medication | Medication Taken Between Week 2 and Week 3 | 67 participants |