Major Depressive Disorder
Conditions
Keywords
Major Depressive Disorder, Depression, Drug Therapy, Major Depressive Episode
Brief summary
The purpose of this study is to determine the efficacy and safety of vortioxetine, once daily (QD), in adults with major depressive disorder.
Detailed description
The drug that was tested in this study is called Vortioxetine. Vortioxetine is being tested to treat depression in adults who have major depressive disorder (MDD). This study looked at MDD relief in people who took varying dosages of vortioxetine. The study enrolled 611 patients. Participants were randomly assigned (by chance, like flipping a coin) to one of the four treatment groups-which remained undisclosed to the patient and study doctor during the study (unless there was an urgent medical need): * Vortioxetine 2.5 mg * Vortioxetine 5 mg * Duloxetine 10 mg * Placebo (dummy inactive capsule) - this was a capsule that looked like the study drug but had no active ingredient. All participants were asked to take one capsule at the same time each day throughout the study. This multi-center trial was conducted in the United States. The overall time to participate in this study was up to 12 weeks. Participants made 8 visits to the clinic, and were contacted by telephone 4 weeks after the last dose of study drug for a follow-up assessment.
Interventions
DRUGVortioxetine
Encapsulated vortioxetine immediate-release tablets
DRUGDuloxetine
Duloxetine capsules
DRUGPlacebo
Placebo-matching capsules
Sponsors
H. Lundbeck A/S
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Suffers from a major depressive episode as the primary diagnosis according to Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) criteria. * The reported duration of the current major depressive episode is at least 3 months.
Exclusion criteria
* Has 1 or more the following: * Any current psychiatric disorder other than major depressive disorder as defined in the DSM-IV-TR. * Current or past history of: manic or hypomanic episode, schizophrenia, or any other psychotic disorder, including major depression with psychotic features, mental retardation, organic mental disorders, or mental disorders due to a general medical condition as defined in the DSM-IV-TR. * Any substance disorder (except nicotine and caffeine) within the previous 6 months as defined in the DSM-IV-TR. * Presence or history of a clinically significant neurological disorder (including epilepsy). * Neurodegenerative disorder (Alzheimer disease, Parkinson disease, multiple sclerosis, Huntington disease, etc). * Any Axis II disorder that might compromise the study. * Has a significant risk of suicide according to the investigator's opinion or has a score ≥5 on item 10 (suicidal thoughts) of the Montgomery Åsberg Depression Rating Scale (MADRS) or has made a suicide attempt in the previous 6 months. * The current depressive symptoms of the patient are considered by the investigator to have been resistant to 2 adequate antidepressant treatments of at least 6 weeks duration each. * Has received electroconvulsive therapy within 6 months prior to Screening. * Is currently receiving formal cognitive or behavioral therapy, systematic psychotherapy, or plans to initiate such therapy during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Week 8 | Baseline and Week 8 | The HAM-D24 is a clinician-rated 24-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 74 where a higher score indicates a greater depressive state. Least squares (LS) means were from an Analysis of Covariance (ANCOVA) model with terms for treatment and center as factors and the Baseline rank value as a covariate. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Responders in HAM-D 24 Total Score by Study Visit | Baseline and Weeks 1, 2, 4, 6 and 8. | A responder is defined as a participant with a ≥50% decrease from Baseline in HAM-D24 total score. The HAM-D24 is a clinician-rated 24-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 74, where a higher score indicates a greater depressive state. |
| Percentage of Participants With a Sustained Response in HAM-D24 | Baseline to Week 8 | A sustained response is defined as a ≥ 20% decrease from Baseline in HAM-D24 total score obtained at Week 1 and sustained through Week 7 and at least 50% decrease from Baseline at Week 8. |
| Percentage of Participants in MADRS Remission at Week 8 | Week 8 | Remission is defined as a participant with a Montgomery Åsberg Depression Rating Scale (MADRS) total score ≤10. The MADRS is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). Decrease in the total score or on individual items indicates improvement. |
| Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score | Baseline and Weeks 1, 2, 4, 6 and 8 | The MADRS is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). A decrease in the total score or on individual items indicates improvement. LS means are from an ANCOVA model with treatment and center as fixed factors and the Baseline value as a covariate. |
| Clinical Global Impression Scale-Global Improvement Scale | Baseline and Weeks 1, 2, 4, 6 and 8. | The Clinical Global Impression - Global Improvement scale assesses the participant's improvement (or worsening) as assessed by the clinician relative to Baseline on a 7-point scale: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. LS means were from an ANCOVA model with treatment and center as fixed factors and the CGI-S Baseline value as a covariate. |
| Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed | Baseline and Weeks 1, 2, 4, and 6 | The HAM-D24 is a clinician-rated 24-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 74 where a higher score indicates a greater depressive state. LS means were from an ANCOVA model with terms for treatment and center as factors and the Baseline rank value as a covariate. |
| Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | Baseline and Weeks 1, 2, 4, 6 and 8. | The HAM-A is an anxiety rating scale consisting of 14 items that assess anxious mood, tension, fear, insomnia, intellectual (cognitive) symptoms, depressed mood, behavior at interview, somatic (sensory), cardiovascular, respiratory, gastrointestinal, genitourinary, autonomic and somatic (muscular) symptoms. Each symptom is rated from 0 (absent) to 4 (maximum severity). Total scores range from 0 to 56, where \<17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. Total scores above 30 are rare, but indicate very severe anxiety. LS means are from an ANCOVA model with treatment and center as fixed factors and the Baseline value as a covariate. |
| Change From Baseline in the Clinical Global Impression Scale-Severity of Illness Scale | Baseline and Weeks 1, 2, 4, 6 and 8. | The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness on the following scale: 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill. LS means were from an ANCOVA model with treatment and center as fixed factors and the Baseline value as a covariate. |
| Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 8 | Baseline and Week 8 | The Sheehan Disability Scale assesses functional impairment in 3 domains: work/school, social life or leisure activities, and home life or family responsibilities. The participant rates the extent to which each aspect is impaired on a 10-point visual analog scale, from 0 (not at all) to 10 (extremely). The 3 scores are added together to calculate the total score, which ranges from 0 to 30, with higher scores indicating more impairment. LS means were from an ANCOVA model with treatment and center as fixed factors and the Baseline value as a covariate. |
| Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Baseline and Week 8 | Healthcare resource utilization was assessed by the Health Economic Assessment (HEA) questionnaire, which monitors participants absenteeism from work, as well as resource use such as visits to a general practitioner, outpatient and inpatient services, hospitalization, medications, and other relevant services over the past 8 weeks. |
| Change From Baseline in Montgomery-Åsberg Depression Rating Scale - Self-assessment (MADRS-S) | Baseline and Weeks 1, 4 and 8 | The MADRS-S is a patient-reported outcome measure based on MADRS, administered to evaluate treatment effectiveness in depression. This scale consists of 9 items assessing patients' mood, feelings of unease, sleep, appetite, ability to concentrate, initiative, emotional involvement, pessimism and zest for life. Each item is scored between 0 (best) and 3 (worst). The total score is calculated by summing the answers of the nine items, ranging between 0 and 27 (higher scores indicate increased impairment). LS means are from an ANCOVA model with treatment and center as fixed factors and the Baseline value as a covariate. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 47 investigative sites in the United States from 10 April 2008 to 30 December 2008.
Pre-assignment details
Participants with a diagnosis of major depressive disorder were enrolled equally in 1 of 4 treatment groups, once a day placebo, 2.5 mg, 5 mg vortioxetine, or 60 mg duloxetine.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo-matching capsules, orally, once daily for up to 9 weeks. | 153 |
| Vortioxetine 2.5 mg Vortioxetine 2.5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period. | 153 |
| Vortioxetine 5 mg Vortioxetine 5 mg, encapsulated tablets, orally, once daily for up to 8 weeks, then placebo-matching capsules, orally, once daily, for 1 week following the treatment period. | 153 |
| Duloxetine 60 mg Duloxetine 60 mg, capsules, orally, once daily for up to 8 weeks, then duloxetine 30 mg capsule, orally, once daily for 1 week after the treatment period. | 152 |
| Total | 611 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 7 | 7 | 12 | 17 |
| Overall Study | Lack of Efficacy | 1 | 2 | 2 | 0 |
| Overall Study | Lost to Follow-up | 8 | 19 | 8 | 11 |
| Overall Study | Noncompliance with Study Drug | 3 | 4 | 0 | 2 |
| Overall Study | Protocol Deviations | 5 | 7 | 2 | 5 |
| Overall Study | Reason not Specified | 3 | 3 | 2 | 1 |
| Overall Study | Withdrawal of Consent | 6 | 12 | 5 | 6 |
Baseline characteristics
| Characteristic | Total | Duloxetine 60 mg | Vortioxetine 5 mg | Vortioxetine 2.5 mg | Placebo |
|---|---|---|---|---|---|
| 24-item Hamilton Depression Scale total score | 29.5 scores on a scale STANDARD_DEVIATION 5.55 | 28.7 scores on a scale STANDARD_DEVIATION 5.08 | 29.8 scores on a scale STANDARD_DEVIATION 5.58 | 29.8 scores on a scale STANDARD_DEVIATION 5.42 | 29.5 scores on a scale STANDARD_DEVIATION 6.05 |
| Age Continuous | 42.7 years STANDARD_DEVIATION 13.7 | 42.7 years STANDARD_DEVIATION 14.38 | 43.1 years STANDARD_DEVIATION 13.89 | 42.6 years STANDARD_DEVIATION 12.85 | 42.6 years STANDARD_DEVIATION 13.76 |
| Age, Customized ≤55 years | 497 participants | 123 participants | 125 participants | 127 participants | 122 participants |
| Age, Customized >55 years | 114 participants | 29 participants | 28 participants | 26 participants | 31 participants |
| Alcohol consumption 2-to-6 times/week | 87 participants | 28 participants | 17 participants | 20 participants | 22 participants |
| Alcohol consumption Daily | 17 participants | 3 participants | 3 participants | 9 participants | 2 participants |
| Alcohol consumption Never | 196 participants | 49 participants | 48 participants | 49 participants | 50 participants |
| Alcohol consumption Once monthly or less often | 218 participants | 51 participants | 62 participants | 49 participants | 56 participants |
| Alcohol consumption Once per week | 93 participants | 21 participants | 23 participants | 26 participants | 23 participants |
| Body Mass Index (BMI) | 30.15 kg/m^2 STANDARD_DEVIATION 7.649 | 30.14 kg/m^2 STANDARD_DEVIATION 6.773 | 31.38 kg/m^2 STANDARD_DEVIATION 8.846 | 29.48 kg/m^2 STANDARD_DEVIATION 7.479 | 29.58 kg/m^2 STANDARD_DEVIATION 7.263 |
| Clinical Global Impression - Severity scale score | 4.5 scores on a scale STANDARD_DEVIATION 0.64 | 4.5 scores on a scale STANDARD_DEVIATION 0.67 | 4.6 scores on a scale STANDARD_DEVIATION 0.65 | 4.6 scores on a scale STANDARD_DEVIATION 0.62 | 4.5 scores on a scale STANDARD_DEVIATION 0.62 |
| Hamilton Anxiety Scale Total Score | 18.5 scores on a scale STANDARD_DEVIATION 5.53 | 17.4 scores on a scale STANDARD_DEVIATION 5.47 | 18.7 scores on a scale STANDARD_DEVIATION 5.74 | 19.3 scores on a scale STANDARD_DEVIATION 5.22 | 18.8 scores on a scale STANDARD_DEVIATION 5.53 |
| Height | 169.21 cm STANDARD_DEVIATION 9.515 | 170.37 cm STANDARD_DEVIATION 9.624 | 167.98 cm STANDARD_DEVIATION 9.833 | 169.50 cm STANDARD_DEVIATION 9.385 | 168.98 cm STANDARD_DEVIATION 9.141 |
| Montgomery Åsberg Depression Rating Scale (MADRS) total score | 29.8 scores on a scale STANDARD_DEVIATION 4.45 | 29.4 scores on a scale STANDARD_DEVIATION 4.31 | 30.1 scores on a scale STANDARD_DEVIATION 4.51 | 29.8 scores on a scale STANDARD_DEVIATION 4.61 | 30.0 scores on a scale STANDARD_DEVIATION 4.39 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 3 participants | 0 participants | 0 participants | 2 participants | 1 participants |
| Race/Ethnicity, Customized Asian | 12 participants | 3 participants | 3 participants | 3 participants | 3 participants |
| Race/Ethnicity, Customized Black | 139 participants | 36 participants | 40 participants | 35 participants | 28 participants |
| Race/Ethnicity, Customized Caucasian (White, including Hispanic) | 452 participants | 111 participants | 108 participants | 112 participants | 121 participants |
| Race/Ethnicity, Customized Hispanic/Latino | 103 participants | 28 participants | 19 participants | 21 participants | 35 participants |
| Race/Ethnicity, Customized Native Hawaiian/ Other Pacific Islander | 2 participants | 1 participants | 0 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Non-Hispanic/Non-Latino | 506 participants | 123 participants | 133 participants | 132 participants | 118 participants |
| Region of Enrollment United States | 611 participants | 152 participants | 153 participants | 153 participants | 153 participants |
| Sex: Female, Male Female | 388 Participants | 91 Participants | 106 Participants | 98 Participants | 93 Participants |
| Sex: Female, Male Male | 223 Participants | 61 Participants | 47 Participants | 55 Participants | 60 Participants |
| Smoking Classification Current smoker | 170 participants | 36 participants | 45 participants | 42 participants | 47 participants |
| Smoking Classification Ex-smoker | 126 participants | 41 participants | 21 participants | 30 participants | 34 participants |
| Smoking Classification Never smoked | 315 participants | 75 participants | 87 participants | 81 participants | 72 participants |
| Weight | 86.34 kg STANDARD_DEVIATION 22.823 | 87.44 kg STANDARD_DEVIATION 20.695 | 88.61 kg STANDARD_DEVIATION 25.779 | 85.08 kg STANDARD_DEVIATION 24.126 | 84.22 kg STANDARD_DEVIATION 20.144 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 81 / 151 | 83 / 149 | 87 / 153 | 120 / 150 |
| serious Total, serious adverse events | 2 / 151 | 0 / 149 | 3 / 153 | 2 / 150 |
Outcome results
Primary
Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Week 8
The HAM-D24 is a clinician-rated 24-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 74 where a higher score indicates a greater depressive state. Least squares (LS) means were from an Analysis of Covariance (ANCOVA) model with terms for treatment and center as factors and the Baseline rank value as a covariate.
Time frame: Baseline and Week 8
Population: The full analysis set (FAS) included all randomized patients who received at least 1 dose of study drug and had at least 1 valid postbaseline value for assessment of primary efficacy. Last observation carried forward (LOCF) was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Week 8 | -10.50 scores on a scale | Standard Error 0.757 |
| Vortioxetine 2.5 mg | Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Week 8 | -12.04 scores on a scale | Standard Error 0.744 |
| Vortioxetine 5 mg | Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Week 8 | -11.08 scores on a scale | Standard Error 0.737 |
| Duloxetine 60 mg | Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Week 8 | -13.47 scores on a scale | Standard Error 0.75 |
Comparison: All statistical tests were 2-sided with 95% confidence intervals (CIs), and with P-values evaluated at the 5% significance level (ie, statistical significance if P\<0.05). To control for multiplicity, a pre-specified sequential testing procedure was applied to compare 5 mg and 2.5 mg vortioxetine to placebo; as soon as an endpoint was non-significant at 0.05, the testing procedure stopped for all subsequent endpoints.p-value: 0.57795% CI: [-2.61, 1.46]ANCOVA
p-value: 0.13895% CI: [-3.58, 0.5]ANCOVA
p-value: 0.00595% CI: [-5.02, -0.91]ANCOVA
Secondary
Change From Baseline in Montgomery-Åsberg Depression Rating Scale - Self-assessment (MADRS-S)
The MADRS-S is a patient-reported outcome measure based on MADRS, administered to evaluate treatment effectiveness in depression. This scale consists of 9 items assessing patients' mood, feelings of unease, sleep, appetite, ability to concentrate, initiative, emotional involvement, pessimism and zest for life. Each item is scored between 0 (best) and 3 (worst). The total score is calculated by summing the answers of the nine items, ranging between 0 and 27 (higher scores indicate increased impairment). LS means are from an ANCOVA model with treatment and center as fixed factors and the Baseline value as a covariate.
Time frame: Baseline and Weeks 1, 4 and 8
Population: Full analysis set with available data at Baseline; LOCF was used. n indicates the number of patients included in the analysis at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Montgomery-Åsberg Depression Rating Scale - Self-assessment (MADRS-S) | Week 1 (n=141, 142, 149, 146) | -2.51 scores on a scale | Standard Error 0.31 |
| Placebo | Change From Baseline in Montgomery-Åsberg Depression Rating Scale - Self-assessment (MADRS-S) | Week 8 (n=148, 145, 152, 149) | -4.25 scores on a scale | Standard Error 0.37 |
| Placebo | Change From Baseline in Montgomery-Åsberg Depression Rating Scale - Self-assessment (MADRS-S) | Week 4 (148, 145, 152, 149) | -4.02 scores on a scale | Standard Error 0.348 |
| Vortioxetine 2.5 mg | Change From Baseline in Montgomery-Åsberg Depression Rating Scale - Self-assessment (MADRS-S) | Week 1 (n=141, 142, 149, 146) | -2.43 scores on a scale | Standard Error 0.299 |
| Vortioxetine 2.5 mg | Change From Baseline in Montgomery-Åsberg Depression Rating Scale - Self-assessment (MADRS-S) | Week 8 (n=148, 145, 152, 149) | -3.98 scores on a scale | Standard Error 0.364 |
| Vortioxetine 2.5 mg | Change From Baseline in Montgomery-Åsberg Depression Rating Scale - Self-assessment (MADRS-S) | Week 4 (148, 145, 152, 149) | -3.65 scores on a scale | Standard Error 0.342 |
| Vortioxetine 5 mg | Change From Baseline in Montgomery-Åsberg Depression Rating Scale - Self-assessment (MADRS-S) | Week 4 (148, 145, 152, 149) | -3.69 scores on a scale | Standard Error 0.338 |
| Vortioxetine 5 mg | Change From Baseline in Montgomery-Åsberg Depression Rating Scale - Self-assessment (MADRS-S) | Week 1 (n=141, 142, 149, 146) | -2.74 scores on a scale | Standard Error 0.295 |
| Vortioxetine 5 mg | Change From Baseline in Montgomery-Åsberg Depression Rating Scale - Self-assessment (MADRS-S) | Week 8 (n=148, 145, 152, 149) | -4.04 scores on a scale | Standard Error 0.36 |
| Duloxetine 60 mg | Change From Baseline in Montgomery-Åsberg Depression Rating Scale - Self-assessment (MADRS-S) | Week 1 (n=141, 142, 149, 146) | -2.88 scores on a scale | Standard Error 0.299 |
| Duloxetine 60 mg | Change From Baseline in Montgomery-Åsberg Depression Rating Scale - Self-assessment (MADRS-S) | Week 8 (n=148, 145, 152, 149) | -5.70 scores on a scale | Standard Error 0.364 |
| Duloxetine 60 mg | Change From Baseline in Montgomery-Åsberg Depression Rating Scale - Self-assessment (MADRS-S) | Week 4 (148, 145, 152, 149) | -4.89 scores on a scale | Standard Error 0.342 |
Secondary
Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 8
The Sheehan Disability Scale assesses functional impairment in 3 domains: work/school, social life or leisure activities, and home life or family responsibilities. The participant rates the extent to which each aspect is impaired on a 10-point visual analog scale, from 0 (not at all) to 10 (extremely). The 3 scores are added together to calculate the total score, which ranges from 0 to 30, with higher scores indicating more impairment. LS means were from an ANCOVA model with treatment and center as fixed factors and the Baseline value as a covariate.
Time frame: Baseline and Week 8
Population: Full analysis set with available data at Baseline; LOCF was used.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 8 | -6.83 scores on a scale | Standard Error 0.638 |
| Vortioxetine 2.5 mg | Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 8 | -6.46 scores on a scale | Standard Error 0.64 |
| Vortioxetine 5 mg | Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 8 | -6.59 scores on a scale | Standard Error 0.641 |
| Duloxetine 60 mg | Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Week 8 | -8.91 scores on a scale | Standard Error 0.672 |
Secondary
Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed
The HAM-D24 is a clinician-rated 24-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 74 where a higher score indicates a greater depressive state. LS means were from an ANCOVA model with terms for treatment and center as factors and the Baseline rank value as a covariate.
Time frame: Baseline and Weeks 1, 2, 4, and 6
Population: Full analysis set; LOCF was used. n indicates the number of patients included in the analysis at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed | Week 1 (n=142, 143, 150, 147) | -5.12 scores on a scale | Standard Error 0.515 |
| Placebo | Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed | Week 2 (n=149, 146, 153, 149) | -7.19 scores on a scale | Standard Error 0.567 |
| Placebo | Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed | Week 4 (n=149, 146, 153, 149) | -9.39 scores on a scale | Standard Error 0.663 |
| Placebo | Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed | Week 6 (n=149, 146, 153, 149) | -10.43 scores on a scale | Standard Error 0.706 |
| Vortioxetine 2.5 mg | Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed | Week 2 (n=149, 146, 153, 149) | -7.95 scores on a scale | Standard Error 0.557 |
| Vortioxetine 2.5 mg | Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed | Week 4 (n=149, 146, 153, 149) | -9.94 scores on a scale | Standard Error 0.651 |
| Vortioxetine 2.5 mg | Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed | Week 6 (n=149, 146, 153, 149) | -11.21 scores on a scale | Standard Error 0.694 |
| Vortioxetine 2.5 mg | Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed | Week 1 (n=142, 143, 150, 147) | -5.44 scores on a scale | Standard Error 0.497 |
| Vortioxetine 5 mg | Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed | Week 4 (n=149, 146, 153, 149) | -8.96 scores on a scale | Standard Error 0.645 |
| Vortioxetine 5 mg | Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed | Week 2 (n=149, 146, 153, 149) | -7.99 scores on a scale | Standard Error 0.552 |
| Vortioxetine 5 mg | Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed | Week 6 (n=149, 146, 153, 149) | -10.97 scores on a scale | Standard Error 0.687 |
| Vortioxetine 5 mg | Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed | Week 1 (n=142, 143, 150, 147) | -5.28 scores on a scale | Standard Error 0.491 |
| Duloxetine 60 mg | Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed | Week 6 (n=149, 146, 153, 149) | -12.78 scores on a scale | Standard Error 0.7 |
| Duloxetine 60 mg | Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed | Week 2 (n=149, 146, 153, 149) | -8.42 scores on a scale | Standard Error 0.562 |
| Duloxetine 60 mg | Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed | Week 1 (n=142, 143, 150, 147) | -5.66 scores on a scale | Standard Error 0.5 |
| Duloxetine 60 mg | Change From Baseline in the 24-item Hamilton Depression Scale Total Score at Other Weeks Assessed | Week 4 (n=149, 146, 153, 149) | -10.88 scores on a scale | Standard Error 0.657 |
Secondary
Change From Baseline in the Clinical Global Impression Scale-Severity of Illness Scale
The Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness on the following scale: 1, normal, not at all ill; 2, borderline mentally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, extremely ill. LS means were from an ANCOVA model with treatment and center as fixed factors and the Baseline value as a covariate.
Time frame: Baseline and Weeks 1, 2, 4, 6 and 8.
Population: Full analysis set; LOCF was used. n indicates the number of patients included in the analysis at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Clinical Global Impression Scale-Severity of Illness Scale | Week 6 (n=149, 146, 153, 149) | -1.11 scores on a scale | Standard Error 0.094 |
| Placebo | Change From Baseline in the Clinical Global Impression Scale-Severity of Illness Scale | Week 2 (n=149, 146, 153, 149) | -0.63 scores on a scale | Standard Error 0.071 |
| Placebo | Change From Baseline in the Clinical Global Impression Scale-Severity of Illness Scale | Week 8 (n=149, 146, 153, 149) | -1.14 scores on a scale | Standard Error 0.103 |
| Placebo | Change From Baseline in the Clinical Global Impression Scale-Severity of Illness Scale | Week 4 (n=149, 146, 153, 149) | -0.92 scores on a scale | Standard Error 0.086 |
| Placebo | Change From Baseline in the Clinical Global Impression Scale-Severity of Illness Scale | Week 1 (n=142, 143, 150, 147) | -0.28 scores on a scale | Standard Error 0.055 |
| Vortioxetine 2.5 mg | Change From Baseline in the Clinical Global Impression Scale-Severity of Illness Scale | Week 4 (n=149, 146, 153, 149) | -0.92 scores on a scale | Standard Error 0.085 |
| Vortioxetine 2.5 mg | Change From Baseline in the Clinical Global Impression Scale-Severity of Illness Scale | Week 6 (n=149, 146, 153, 149) | -1.08 scores on a scale | Standard Error 0.092 |
| Vortioxetine 2.5 mg | Change From Baseline in the Clinical Global Impression Scale-Severity of Illness Scale | Week 8 (n=149, 146, 153, 149) | -1.21 scores on a scale | Standard Error 0.102 |
| Vortioxetine 2.5 mg | Change From Baseline in the Clinical Global Impression Scale-Severity of Illness Scale | Week 2 (n=149, 146, 153, 149) | -0.65 scores on a scale | Standard Error 0.069 |
| Vortioxetine 2.5 mg | Change From Baseline in the Clinical Global Impression Scale-Severity of Illness Scale | Week 1 (n=142, 143, 150, 147) | -0.40 scores on a scale | Standard Error 0.053 |
| Vortioxetine 5 mg | Change From Baseline in the Clinical Global Impression Scale-Severity of Illness Scale | Week 4 (n=149, 146, 153, 149) | -0.90 scores on a scale | Standard Error 0.084 |
| Vortioxetine 5 mg | Change From Baseline in the Clinical Global Impression Scale-Severity of Illness Scale | Week 1 (n=142, 143, 150, 147) | -0.37 scores on a scale | Standard Error 0.053 |
| Vortioxetine 5 mg | Change From Baseline in the Clinical Global Impression Scale-Severity of Illness Scale | Week 2 (n=149, 146, 153, 149) | -0.66 scores on a scale | Standard Error 0.069 |
| Vortioxetine 5 mg | Change From Baseline in the Clinical Global Impression Scale-Severity of Illness Scale | Week 6 (n=149, 146, 153, 149) | -1.08 scores on a scale | Standard Error 0.091 |
| Vortioxetine 5 mg | Change From Baseline in the Clinical Global Impression Scale-Severity of Illness Scale | Week 8 (n=149, 146, 153, 149) | -1.17 scores on a scale | Standard Error 0.101 |
| Duloxetine 60 mg | Change From Baseline in the Clinical Global Impression Scale-Severity of Illness Scale | Week 6 (n=149, 146, 153, 149) | -1.39 scores on a scale | Standard Error 0.093 |
| Duloxetine 60 mg | Change From Baseline in the Clinical Global Impression Scale-Severity of Illness Scale | Week 2 (n=149, 146, 153, 149) | -0.75 scores on a scale | Standard Error 0.07 |
| Duloxetine 60 mg | Change From Baseline in the Clinical Global Impression Scale-Severity of Illness Scale | Week 1 (n=142, 143, 150, 147) | -0.44 scores on a scale | Standard Error 0.054 |
| Duloxetine 60 mg | Change From Baseline in the Clinical Global Impression Scale-Severity of Illness Scale | Week 4 (n=149, 146, 153, 149) | -1.12 scores on a scale | Standard Error 0.085 |
| Duloxetine 60 mg | Change From Baseline in the Clinical Global Impression Scale-Severity of Illness Scale | Week 8 (n=149, 146, 153, 149) | -1.56 scores on a scale | Standard Error 0.102 |
Secondary
Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score
The HAM-A is an anxiety rating scale consisting of 14 items that assess anxious mood, tension, fear, insomnia, intellectual (cognitive) symptoms, depressed mood, behavior at interview, somatic (sensory), cardiovascular, respiratory, gastrointestinal, genitourinary, autonomic and somatic (muscular) symptoms. Each symptom is rated from 0 (absent) to 4 (maximum severity). Total scores range from 0 to 56, where \<17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe. Total scores above 30 are rare, but indicate very severe anxiety. LS means are from an ANCOVA model with treatment and center as fixed factors and the Baseline value as a covariate.
Time frame: Baseline and Weeks 1, 2, 4, 6 and 8.
Population: Full analysis set; LOCF was used. n indicates the number of patients included in the analysis at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | Week 6 (n=149, 146, 153, 149) | -5.84 scores on a scale | Standard Error 0.482 |
| Placebo | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | Week 2 (n=149, 146, 153, 149) | -3.82 scores on a scale | Standard Error 0.419 |
| Placebo | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | Week 8 (n=149, 146, 153, 149) | -5.75 scores on a scale | Standard Error 0.502 |
| Placebo | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | Week 4 (n=149, 146, 153, 149) | -5.12 scores on a scale | Standard Error 0.457 |
| Placebo | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | Week 1 (n=142, 143, 150, 147) | -2.63 scores on a scale | Standard Error 0.356 |
| Vortioxetine 2.5 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | Week 4 (n=149, 146, 153, 149) | -5.10 scores on a scale | Standard Error 0.45 |
| Vortioxetine 2.5 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | Week 6 (n=149, 146, 153, 149) | -5.77 scores on a scale | Standard Error 0.474 |
| Vortioxetine 2.5 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | Week 8 (n=149, 146, 153, 149) | -5.91 scores on a scale | Standard Error 0.494 |
| Vortioxetine 2.5 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | Week 2 (n=149, 146, 153, 149) | -4.41 scores on a scale | Standard Error 0.412 |
| Vortioxetine 2.5 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | Week 1 (n=142, 143, 150, 147) | -2.98 scores on a scale | Standard Error 0.343 |
| Vortioxetine 5 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | Week 4 (n=149, 146, 153, 149) | -4.25 scores on a scale | Standard Error 0.445 |
| Vortioxetine 5 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | Week 1 (n=142, 143, 150, 147) | -2.55 scores on a scale | Standard Error 0.339 |
| Vortioxetine 5 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | Week 2 (n=149, 146, 153, 149) | -3.76 scores on a scale | Standard Error 0.408 |
| Vortioxetine 5 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | Week 6 (n=149, 146, 153, 149) | -4.89 scores on a scale | Standard Error 0.469 |
| Vortioxetine 5 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | Week 8 (n=149, 146, 153, 149) | -5.29 scores on a scale | Standard Error 0.488 |
| Duloxetine 60 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | Week 6 (n=149, 146, 153, 149) | -6.15 scores on a scale | Standard Error 0.478 |
| Duloxetine 60 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | Week 2 (n=149, 146, 153, 149) | -3.94 scores on a scale | Standard Error 0.415 |
| Duloxetine 60 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | Week 1 (n=142, 143, 150, 147) | -2.30 scores on a scale | Standard Error 0.346 |
| Duloxetine 60 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | Week 4 (n=149, 146, 153, 149) | -4.88 scores on a scale | Standard Error 0.454 |
| Duloxetine 60 mg | Change From Baseline in the Hamilton Anxiety Scale (HAM-A) Total Score | Week 8 (n=149, 146, 153, 149) | -6.56 scores on a scale | Standard Error 0.498 |
Secondary
Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score
The MADRS is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). A decrease in the total score or on individual items indicates improvement. LS means are from an ANCOVA model with treatment and center as fixed factors and the Baseline value as a covariate.
Time frame: Baseline and Weeks 1, 2, 4, 6 and 8
Population: Full analysis set; LOCF was used. n indicates the number of patients included in the analysis at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score | Week 6 (n=149, 146, 153, 149) | -11.04 scores on a scale | Standard Error 0.77 |
| Placebo | Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score | Week 2 (n=149, 146, 153, 149) | -7.57 scores on a scale | Standard Error 0.615 |
| Placebo | Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score | Week 8 (149, 146, 153, 149) | -11.22 scores on a scale | Standard Error 0.819 |
| Placebo | Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score | Week 4 (n=149, 146, 153, 149) | -9.66 scores on a scale | Standard Error 0.693 |
| Placebo | Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score | Week 1 (n=142, 143, 150, 147) | -4.90 scores on a scale | Standard Error 0.53 |
| Vortioxetine 2.5 mg | Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score | Week 4 (n=149, 146, 153, 149) | -9.58 scores on a scale | Standard Error 0.681 |
| Vortioxetine 2.5 mg | Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score | Week 6 (n=149, 146, 153, 149) | -11.25 scores on a scale | Standard Error 0.757 |
| Vortioxetine 2.5 mg | Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score | Week 8 (149, 146, 153, 149) | -11.61 scores on a scale | Standard Error 0.805 |
| Vortioxetine 2.5 mg | Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score | Week 2 (n=149, 146, 153, 149) | -7.71 scores on a scale | Standard Error 0.605 |
| Vortioxetine 2.5 mg | Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score | Week 1 (n=142, 143, 150, 147) | -5.16 scores on a scale | Standard Error 0.511 |
| Vortioxetine 5 mg | Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score | Week 4 (n=149, 146, 153, 149) | -9.35 scores on a scale | Standard Error 0.675 |
| Vortioxetine 5 mg | Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score | Week 1 (n=142, 143, 150, 147) | -5.06 scores on a scale | Standard Error 0.505 |
| Vortioxetine 5 mg | Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score | Week 2 (n=149, 146, 153, 149) | -7.81 scores on a scale | Standard Error 0.599 |
| Vortioxetine 5 mg | Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score | Week 6 (n=149, 146, 153, 149) | -11.27 scores on a scale | Standard Error 0.75 |
| Vortioxetine 5 mg | Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score | Week 8 (149, 146, 153, 149) | -11.30 scores on a scale | Standard Error 0.797 |
| Duloxetine 60 mg | Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score | Week 6 (n=149, 146, 153, 149) | -13.29 scores on a scale | Standard Error 0.763 |
| Duloxetine 60 mg | Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score | Week 2 (n=149, 146, 153, 149) | -8.95 scores on a scale | Standard Error 0.609 |
| Duloxetine 60 mg | Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score | Week 1 (n=142, 143, 150, 147) | -5.49 scores on a scale | Standard Error 0.514 |
| Duloxetine 60 mg | Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score | Week 4 (n=149, 146, 153, 149) | -11.34 scores on a scale | Standard Error 0.686 |
| Duloxetine 60 mg | Change From Baseline in the Montgomery Åsberg Depression Rating Scale (MADRS) Total Score | Week 8 (149, 146, 153, 149) | -14.10 scores on a scale | Standard Error 0.811 |
Secondary
Clinical Global Impression Scale-Global Improvement Scale
The Clinical Global Impression - Global Improvement scale assesses the participant's improvement (or worsening) as assessed by the clinician relative to Baseline on a 7-point scale: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. LS means were from an ANCOVA model with treatment and center as fixed factors and the CGI-S Baseline value as a covariate.
Time frame: Baseline and Weeks 1, 2, 4, 6 and 8.
Population: Full analysis set; LOCF was used. n indicates the number of patients included in the analysis at each time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Clinical Global Impression Scale-Global Improvement Scale | Week 6 (149, 146, 153, 149) | 2.83 scores on a scale | Standard Error 0.091 |
| Placebo | Clinical Global Impression Scale-Global Improvement Scale | Week 2 (n=149, 146, 153, 149) | 3.21 scores on a scale | Standard Error 0.077 |
| Placebo | Clinical Global Impression Scale-Global Improvement Scale | Week 8 (n=149, 146, 153, 149) | 2.79 scores on a scale | Standard Error 0.098 |
| Placebo | Clinical Global Impression Scale-Global Improvement Scale | Week 4 (149, 146, 153, 149) | 2.97 scores on a scale | Standard Error 0.085 |
| Placebo | Clinical Global Impression Scale-Global Improvement Scale | Week 1 (n=142, 143, 149, 147) | 3.54 scores on a scale | Standard Error 0.067 |
| Vortioxetine 2.5 mg | Clinical Global Impression Scale-Global Improvement Scale | Week 4 (149, 146, 153, 149) | 2.93 scores on a scale | Standard Error 0.084 |
| Vortioxetine 2.5 mg | Clinical Global Impression Scale-Global Improvement Scale | Week 6 (149, 146, 153, 149) | 2.82 scores on a scale | Standard Error 0.09 |
| Vortioxetine 2.5 mg | Clinical Global Impression Scale-Global Improvement Scale | Week 8 (n=149, 146, 153, 149) | 2.73 scores on a scale | Standard Error 0.096 |
| Vortioxetine 2.5 mg | Clinical Global Impression Scale-Global Improvement Scale | Week 2 (n=149, 146, 153, 149) | 3.17 scores on a scale | Standard Error 0.076 |
| Vortioxetine 2.5 mg | Clinical Global Impression Scale-Global Improvement Scale | Week 1 (n=142, 143, 149, 147) | 3.42 scores on a scale | Standard Error 0.065 |
| Vortioxetine 5 mg | Clinical Global Impression Scale-Global Improvement Scale | Week 4 (149, 146, 153, 149) | 2.87 scores on a scale | Standard Error 0.083 |
| Vortioxetine 5 mg | Clinical Global Impression Scale-Global Improvement Scale | Week 1 (n=142, 143, 149, 147) | 3.46 scores on a scale | Standard Error 0.064 |
| Vortioxetine 5 mg | Clinical Global Impression Scale-Global Improvement Scale | Week 2 (n=149, 146, 153, 149) | 3.10 scores on a scale | Standard Error 0.075 |
| Vortioxetine 5 mg | Clinical Global Impression Scale-Global Improvement Scale | Week 6 (149, 146, 153, 149) | 2.74 scores on a scale | Standard Error 0.089 |
| Vortioxetine 5 mg | Clinical Global Impression Scale-Global Improvement Scale | Week 8 (n=149, 146, 153, 149) | 2.63 scores on a scale | Standard Error 0.095 |
| Duloxetine 60 mg | Clinical Global Impression Scale-Global Improvement Scale | Week 6 (149, 146, 153, 149) | 2.50 scores on a scale | Standard Error 0.09 |
| Duloxetine 60 mg | Clinical Global Impression Scale-Global Improvement Scale | Week 2 (n=149, 146, 153, 149) | 2.99 scores on a scale | Standard Error 0.076 |
| Duloxetine 60 mg | Clinical Global Impression Scale-Global Improvement Scale | Week 1 (n=142, 143, 149, 147) | 3.31 scores on a scale | Standard Error 0.065 |
| Duloxetine 60 mg | Clinical Global Impression Scale-Global Improvement Scale | Week 4 (149, 146, 153, 149) | 2.73 scores on a scale | Standard Error 0.084 |
| Duloxetine 60 mg | Clinical Global Impression Scale-Global Improvement Scale | Week 8 (n=149, 146, 153, 149) | 2.39 scores on a scale | Standard Error 0.097 |
Secondary
Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire
Healthcare resource utilization was assessed by the Health Economic Assessment (HEA) questionnaire, which monitors participants absenteeism from work, as well as resource use such as visits to a general practitioner, outpatient and inpatient services, hospitalization, medications, and other relevant services over the past 8 weeks.
Time frame: Baseline and Week 8
Population: Full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Baseline: Sick leave related to depression | 13 participants |
| Placebo | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Baseline: Any resource use | 40 participants |
| Placebo | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Baseline: Any hospitalization-related services | 4 participants |
| Placebo | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Baseline: Hospitalization related to depression | 2 participants |
| Placebo | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Baseline: Any sick leave | 18 participants |
| Placebo | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Week 8: Any resource use | 21 participants |
| Placebo | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Week 8: Any hospitalization-related service | 1 participants |
| Placebo | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Week 8: Hospitalization related to depression | 0 participants |
| Placebo | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Week 8: Any sick leave | 5 participants |
| Placebo | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Week 8: Sick leave related to depression | 2 participants |
| Vortioxetine 2.5 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Week 8: Any sick leave | 5 participants |
| Vortioxetine 2.5 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Baseline: Any sick leave | 11 participants |
| Vortioxetine 2.5 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Baseline: Sick leave related to depression | 9 participants |
| Vortioxetine 2.5 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Week 8: Any resource use | 19 participants |
| Vortioxetine 2.5 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Week 8: Any hospitalization-related service | 0 participants |
| Vortioxetine 2.5 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Week 8: Sick leave related to depression | 4 participants |
| Vortioxetine 2.5 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Week 8: Hospitalization related to depression | 0 participants |
| Vortioxetine 2.5 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Baseline: Any resource use | 51 participants |
| Vortioxetine 2.5 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Baseline: Any hospitalization-related services | 1 participants |
| Vortioxetine 2.5 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Baseline: Hospitalization related to depression | 1 participants |
| Vortioxetine 5 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Week 8: Hospitalization related to depression | 0 participants |
| Vortioxetine 5 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Baseline: Hospitalization related to depression | 0 participants |
| Vortioxetine 5 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Week 8: Any hospitalization-related service | 1 participants |
| Vortioxetine 5 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Week 8: Any sick leave | 9 participants |
| Vortioxetine 5 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Week 8: Any resource use | 20 participants |
| Vortioxetine 5 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Baseline: Any sick leave | 11 participants |
| Vortioxetine 5 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Week 8: Sick leave related to depression | 3 participants |
| Vortioxetine 5 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Baseline: Any hospitalization-related services | 0 participants |
| Vortioxetine 5 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Baseline: Sick leave related to depression | 10 participants |
| Vortioxetine 5 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Baseline: Any resource use | 42 participants |
| Duloxetine 60 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Baseline: Sick leave related to depression | 11 participants |
| Duloxetine 60 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Week 8: Any resource use | 27 participants |
| Duloxetine 60 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Week 8: Sick leave related to depression | 2 participants |
| Duloxetine 60 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Baseline: Any resource use | 42 participants |
| Duloxetine 60 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Week 8: Any hospitalization-related service | 2 participants |
| Duloxetine 60 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Baseline: Any hospitalization-related services | 3 participants |
| Duloxetine 60 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Baseline: Hospitalization related to depression | 0 participants |
| Duloxetine 60 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Week 8: Hospitalization related to depression | 1 participants |
| Duloxetine 60 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Baseline: Any sick leave | 14 participants |
| Duloxetine 60 mg | Healthcare Resource Utilization as Assessed by the Health Economic Assessment Questionnaire | Week 8: Any sick leave | 5 participants |
Secondary
Percentage of Participants in MADRS Remission at Week 8
Remission is defined as a participant with a Montgomery Åsberg Depression Rating Scale (MADRS) total score ≤10. The MADRS is a depression rating scale consisting of 10 items, each rated 0 to 6. The 10 items represent the core symptoms of depressive illness. The overall score ranges from 0 (symptoms absent) to 60 (severe depression). Decrease in the total score or on individual items indicates improvement.
Time frame: Week 8
Population: Full analysis set; LOCF was used.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants in MADRS Remission at Week 8 | 22.8 percentage of participants |
| Vortioxetine 2.5 mg | Percentage of Participants in MADRS Remission at Week 8 | 28.8 percentage of participants |
| Vortioxetine 5 mg | Percentage of Participants in MADRS Remission at Week 8 | 23.5 percentage of participants |
| Duloxetine 60 mg | Percentage of Participants in MADRS Remission at Week 8 | 37.6 percentage of participants |
Secondary
Percentage of Participants With a Sustained Response in HAM-D24
A sustained response is defined as a ≥ 20% decrease from Baseline in HAM-D24 total score obtained at Week 1 and sustained through Week 7 and at least 50% decrease from Baseline at Week 8.
Time frame: Baseline to Week 8
Population: Full analysis set with available data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With a Sustained Response in HAM-D24 | 12.1 percentage of participants |
| Vortioxetine 2.5 mg | Percentage of Participants With a Sustained Response in HAM-D24 | 15.8 percentage of participants |
| Vortioxetine 5 mg | Percentage of Participants With a Sustained Response in HAM-D24 | 17.0 percentage of participants |
| Duloxetine 60 mg | Percentage of Participants With a Sustained Response in HAM-D24 | 21.5 percentage of participants |
Secondary
Percentage of Responders in HAM-D 24 Total Score by Study Visit
A responder is defined as a participant with a ≥50% decrease from Baseline in HAM-D24 total score. The HAM-D24 is a clinician-rated 24-item scale for assessing the severity of depression symptoms. The scores for each item range from 0 to 4 or 0 to 2, where 0 represents no symptoms. The rating is based on the past 7 days prior to the time of assessment. The total score ranges from 0 to 74, where a higher score indicates a greater depressive state.
Time frame: Baseline and Weeks 1, 2, 4, 6 and 8.
Population: Full analysis set; LOCF was used. n indicates the number of patients included in the analysis at each time point.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Responders in HAM-D 24 Total Score by Study Visit | Week 6 (n=149, 146, 153, 149) | 32.9 percentage of participants |
| Placebo | Percentage of Responders in HAM-D 24 Total Score by Study Visit | Week 2 (n=149, 146, 153, 149) | 15.4 percentage of participants |
| Placebo | Percentage of Responders in HAM-D 24 Total Score by Study Visit | Week 8 (n=149, 146, 153, 149) | 32.2 percentage of participants |
| Placebo | Percentage of Responders in HAM-D 24 Total Score by Study Visit | Week 4 (n=149, 146, 153, 149) | 26.2 percentage of participants |
| Placebo | Percentage of Responders in HAM-D 24 Total Score by Study Visit | Week 1 (n=142, 143, 150, 147) | 9.2 percentage of participants |
| Vortioxetine 2.5 mg | Percentage of Responders in HAM-D 24 Total Score by Study Visit | Week 4 (n=149, 146, 153, 149) | 30.8 percentage of participants |
| Vortioxetine 2.5 mg | Percentage of Responders in HAM-D 24 Total Score by Study Visit | Week 6 (n=149, 146, 153, 149) | 37.7 percentage of participants |
| Vortioxetine 2.5 mg | Percentage of Responders in HAM-D 24 Total Score by Study Visit | Week 8 (n=149, 146, 153, 149) | 41.1 percentage of participants |
| Vortioxetine 2.5 mg | Percentage of Responders in HAM-D 24 Total Score by Study Visit | Week 2 (n=149, 146, 153, 149) | 17.1 percentage of participants |
| Vortioxetine 2.5 mg | Percentage of Responders in HAM-D 24 Total Score by Study Visit | Week 1 (n=142, 143, 150, 147) | 8.4 percentage of participants |
| Vortioxetine 5 mg | Percentage of Responders in HAM-D 24 Total Score by Study Visit | Week 4 (n=149, 146, 153, 149) | 24.2 percentage of participants |
| Vortioxetine 5 mg | Percentage of Responders in HAM-D 24 Total Score by Study Visit | Week 1 (n=142, 143, 150, 147) | 8.7 percentage of participants |
| Vortioxetine 5 mg | Percentage of Responders in HAM-D 24 Total Score by Study Visit | Week 2 (n=149, 146, 153, 149) | 17.6 percentage of participants |
| Vortioxetine 5 mg | Percentage of Responders in HAM-D 24 Total Score by Study Visit | Week 6 (n=149, 146, 153, 149) | 37.3 percentage of participants |
| Vortioxetine 5 mg | Percentage of Responders in HAM-D 24 Total Score by Study Visit | Week 8 (n=149, 146, 153, 149) | 37.9 percentage of participants |
| Duloxetine 60 mg | Percentage of Responders in HAM-D 24 Total Score by Study Visit | Week 6 (n=149, 146, 153, 149) | 47.0 percentage of participants |
| Duloxetine 60 mg | Percentage of Responders in HAM-D 24 Total Score by Study Visit | Week 2 (n=149, 146, 153, 149) | 22.1 percentage of participants |
| Duloxetine 60 mg | Percentage of Responders in HAM-D 24 Total Score by Study Visit | Week 1 (n=142, 143, 150, 147) | 10.2 percentage of participants |
| Duloxetine 60 mg | Percentage of Responders in HAM-D 24 Total Score by Study Visit | Week 4 (n=149, 146, 153, 149) | 34.9 percentage of participants |
| Duloxetine 60 mg | Percentage of Responders in HAM-D 24 Total Score by Study Visit | Week 8 (n=149, 146, 153, 149) | 51.0 percentage of participants |