Major Depressive Disorder
Conditions
Keywords
Major Depressive Disorder, MDD, Depression
Brief summary
This study investigates two different approaches to the change in antidepressant treatment when an initial treatment is not effective: early intervention or delayed intervention. Two hypothesis will be tested: 1. that time to confirmed response is shorter in the early intervention strategy vs. delayed intervention strategy 2. that the time to confirmed remission is shorter in the early intervention strategy compared to delayed intervention strategy.
Interventions
DRUGDuloxetine Hydrochloride
Flexible dose of 60 or 120 mg daily
DRUGEscitalopram
10 mg in both Early and Delayed Intervention. Flexible dose of 10 to 20 mg daily in Delayed Intervention.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female participants of at least 18 years of age who meet criteria for Major Depressive Disorder (MDD), single or recurrent episode according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV®-TR) disease diagnostic criteria. 2. Participants (receiving or not antidepressant treatment) who, based on investigator criteria, initiate treatment with escitalopram or change their current Alzheimer's Disease (AD) treatment to escitalopram for this current MDD episode, at the initial visit. 3. Must have a baseline score of ≥ 19 on the 17-item Hamilton Depression Rating Scale (HAMD-17) at the initial visit. 4. Must have a baseline score of ≥ 4 in the Clinical Global Impression-Severity Scale (CGI-S) at the initial visit. 5. Have a level of understanding sufficient to provide Informed Consent Document (ICD), and to communicate with the investigators and site personnel. 6. Are judged to be reliable and agree to keep all appointments for clinic visits and procedures required by the protocol.
Exclusion criteria
7. Have any current primary Axis I disorder other than MDD, including but not limited to dysthymia. 8. Have a diagnosis of dementia, Alzheimer's disease (AD), or organic brain syndrome; or who are cognitively impaired or who have language problems that prevent them from understanding and/or providing valid answers to the rating scale contents. 9. Concomitant participation in other studies with investigational or marketed products. 10. Are not expected to be able to be monitored throughout the entire study period for reasons unrelated to their illness (for instance, change of residence or healthcare center of reference). 11. Are demonstrating a response or demonstrated a response to the AD treatment for the current depression episode previous to baseline visit. 12. Are investigator site personnel directly affiliated with this study and/or their immediate families. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted. 13. Are employed by Lilly or Boehringer Ingelheim (BI) (that is, employees, temporary contract workers, or designees responsible for the conduct of the study). Immediate family of Lilly or BI employees may participate in Lilly or BI-sponsored clinical trials, but are not permitted to participate at a Lilly or BI facility. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted. 14. Women of childbearing potential who are not using a medically accepted means of contraception (for example, intrauterine device, oral contraceptive, contraceptive patch, implant, Depo-Provera \[medroxyprogesterone acetate injectable suspension, Pharmacia & Upjohn\], or barrier devices) when engaging in sexual intercourse. Women who are pregnant or breast-feeding may not participate in the study. 15. Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at the time of study entry. 16. Are judged to be at serious suicidal risk in the opinion of the investigator, and/or if the participant's baseline (Visit 1) HAMD-17 scores on item 3 suicide are 3. 17. Have been treated with a monoamine oxidase inhibitor (MAOI) within 14 days prior to Visit 1 or potential need to use an MAOI during the study or within 5 days after discontinuation of study drug. 18. Require initiation or discontinuation of psychotherapy within 6 weeks prior to enrollment (Visit 1) or at any time during the study. 19. Have any contraindication for the use of duloxetine based on Duloxetine Summary of Product Characteristics (SPC) or any contraindication for the use of escitalopram based on Escitalopram SPC. 20. Have a history of lack of response to duloxetine or escitalopram at a clinically appropriate dose for a minimum of 4 weeks, or have previously completed or withdrawn from this study or any other study investigating duloxetine or escitalopram. 21. Have any previous diagnosis of bipolar disorder, schizophrenia, or other psychotic disorders. 22. Have DSM-IV-defined history of substance abuse or dependence within the past year, excluding nicotine and caffeine. 23. Have serious or unstable cardiovascular, hepatic, renal, respiratory or hematological illness; symptomatic peripheral vascular disease; or other medical (including unstable hypertension and not clinically euthyroid) or psychological conditions that, in the opinion of the investigator, would compromise participation or be likely to require hospitalization during the course of the study. 24. Have had Electroconvulsive Therapy (ECT) or Transcranial Magnetic Stimulation within the past year.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Confirmed Response by ≥ 50% Change From Baseline Reduction in the Hamilton Depression Rating Scale-17 Items (HAMD-17) | Week 4 through Week 16 | Time to confirmed response is defined as the time from the day of study randomization (Visit 2) to the date of first observation of confirmed response defined as ≥ 50% baseline score reduction on the HAMD-17 for 2 consecutive visits. The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale, e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe). |
| Estimated Probability of Not Reaching Confirmed Response at 12 Weeks Based on the Survival Function for the Time to Confirmed Response | Week 4 through Week 16 | Survival function is estimating the probability of participants not achieving confirmed response after 12 weeks. Confirmed response is defined as \>=50% change from baseline reduction in the Hamilton Depression Rating Scale-17 Items (HAMD-17). The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe). |
| Time to Confirmed Remission by a Hamilton Depression Rating Scale-17 Items (HAMD-17) Score of ≤ 7 That is Maintained for Two Consecutive Visits | Week 4 through Week 16 | Time to confirmed remission is defined as the time from the day of study randomization (Visit 2) to the date of first observation of confirmed remission defined as a score on the HAMD-17 of ≤ 7 for 2 consecutive visits. The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe). |
| Estimated Probability of Not Reaching Confirmed Remission at 12 Weeks Based on the Survival Function for the Time to Confirmed Remission | Week 4 through Week 16 | Survival function is estimating the probability of participants not achieving confirmed remission. Confirmed remission is defined as a Hamilton Depression Rating Scale-17 Items (HAMD-17) Score of ≤ 7 that is maintained for two consecutive visits. The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Euro Quality of Life Questionnaire-5 Dimensions (EQ-5D) Scale - Health State Score | Baseline, Week 4, Week 8, Week 12, Week 16 | The EQ-5D Health State Score is self-rated health on a vertical, visual analogue scale measured in centimeters (cm) and reported as units on a scale. Best imaginable health state = 10 cm and worst imaginable health state = 0 cm. |
| Euro Quality of Life Questionnaire-5 Dimensions (EQ-5D) Scale - United Kingdom (UK) Population Based Index Score | Baseline, Week 4, Week 8, Week 12, Week 16 | The EQ-5D is a generic, multidimensional, health-related, quality of life instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood. A single score between 1 and 3 is generated for each domain. For each participant, the outcome rating on the 5 domains will be mapped to a single index through an algorithm. The index ranges between 0 and 1, with the higher score indicating a better health state perceived by the participant. |
| Sheehan Disability Scale (SDS) Normal Functioning Total Score | Baseline, Week 4, Week 8, Week 12, Week 16 | The SDS is completed by the participant and is used to assess the effect of the participant's symptoms on their work/social/family life. Total scores range from 0 to 30 with higher values indicating greater disruption in the participant's work/social/family life. |
| Resource Utilisation - Number of Hours Worked Per Week | Baseline, Week 4, Week 8, Week 12, Week 16 | — |
| Resource Utilisation - Number of Work Hours Missed in the Last 4 Weeks | Week 4, Week 8, Week 12, Week 16 | Only those participants who missed at least 1 hour of work were included. |
| Time to Confirmed Response as Defined by ≥ 50% Reduction From Baseline Reduction in the 16-Item Quick Inventory of Depressive Symptomatology Self Report (QIDS16SR) That is Reported for Two Consecutive Visits | Week 4 through Week 16 | Time to confirmed response is defined as the time from the day of study randomization (Visit 2) to the date of first observation of confirmed response. QIDS16SR is a 16-item participant-rated measure of depressive symptomatology. The total score ranges from 0 to 27 with higher scores indicative of greater severity. |
| Resource Utilisation - Number of Visits to Primary Healthcare Provider Due to Depression in the Last 4 Weeks | Week 4, Week 8, Week 12, Week 16 | — |
| Resource Utilisation - Number of Visits to Other Specialists Due to Depression in the Last 4 Weeks | Week 4, Week 8, Week 12, Week 16 | — |
| Resource Utilisation - Has the Participant Been Hospitalized Due to Depression in the Last 4 Weeks - Number of Participants With a Yes Response | Week 4, Week 8, Week 12, Week 16 | — |
| Number of Participants With Adverse Events (AEs) | Baseline through Week 16 | The list of AEs is located in the Reported Adverse Event module. |
| Resource Utilisation - Number of Work Hours Missed Due to Depression in the Last 4 Weeks | Week 4, Week 8, Week 12, Week 16 | Only those participants who missed at least 1 hour of work due to depression were included. |
| Time to Confirmed Remission as Defined by a 16-Item Quick Inventory of Depressive Symptomatology Self Report (QIDS16SR) Score of ≤ 5 That is Maintained for Two Consecutive Visits. | Week 4 through Week 16 | Time to confirmed remission is defined as the time from the day of study randomization (Visit 2) to the date of first observation of confirmed remission. A 16-item participant-rated measure of depressive symptomatology. The total score ranges from 0 to 27 with higher scores indicative of greater severity. |
| Clinical Global Impressions of Severity (CGI-S) Scale | Baseline, Week 4, Week 6, Week 8, Week 10, Week 12, Week 14, Week 16 | Measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants). |
| Visual Analog Scale (VAS) - Overall Pain Severity | Baseline, Week 4, Week 6, Week 8, Week 10, Week 12, Week 14, Week 16 | VAS for pain consists of 6 questions that assess overall pain, headache, back pain, shoulder pain, pain interference with daily activities, and pain while awake. Participant rates pain on a 10 centimeter (cm) line between two anchors (0= no pain and 10=very severe pain). |
Countries
Denmark, France, Greece, Hungary, Italy, Netherlands, Romania, Slovenia, Spain, Sweden, Turkey (Türkiye)
Participant flow
Recruitment details
Participants showing improvement (≥30% baseline score reduction on the HAMD-17) during Period I did not continue to Period II of the study. Qualified participants for Period II were randomized to either Early Intervention Strategy Arm or Delayed Intervention Strategy Arm.
Pre-assignment details
Baseline demographics and primary and secondary outcomes are reported only for Period II (Double Blind Treatment Strategy). Adverse events (AEs) are reported for Period I (Acute Escitalopram Treatment) and Period II.
Participants by arm
| Arm | Count |
|---|---|
| Early Intervention Duloxetine flexible dose (60 or 120 milligrams \[mg\] daily) for 12 weeks | 282 |
| Delayed Intervention Escitalopram flexible dose (10 to 20 milligrams \[mg\] daily) for 4 weeks. Then in participants with no-response, switch treatment to duloxetine flexible dose (60 or 120 mg daily) for 8 weeks. In participants with a response continue treatment with escitalopram (10 to 20 milligrams \[mg\] daily) for 8 weeks. | 284 |
| Total | 566 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Double-Blind Period II | Adverse Event | 0 | 9 | 8 |
| Double-Blind Period II | Clinical relapse | 0 | 3 | 0 |
| Double-Blind Period II | Lack of Efficacy | 0 | 7 | 12 |
| Double-Blind Period II | Lost to Follow-up | 0 | 9 | 9 |
| Double-Blind Period II | Physician Decision | 0 | 0 | 1 |
| Double-Blind Period II | Protocol entry criterion not met | 0 | 0 | 1 |
| Double-Blind Period II | Protocol Violation | 0 | 7 | 6 |
| Double-Blind Period II | Withdrawal by Subject | 0 | 21 | 35 |
| Lead-in Period I | Adverse Event | 43 | 0 | 0 |
| Lead-in Period I | Lack of Efficacy | 1 | 0 | 0 |
| Lead-in Period I | Lost to Follow-up | 19 | 0 | 0 |
| Lead-in Period I | Physician Decision | 1 | 0 | 0 |
| Lead-in Period I | Protocol entry criterion not met | 5 | 0 | 0 |
| Lead-in Period I | Protocol Violation | 1 | 0 | 0 |
| Lead-in Period I | Randomization criteria not met | 158 | 0 | 0 |
| Lead-in Period I | Withdrawal by Subject | 46 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Delayed Intervention | Early Intervention |
|---|---|---|---|
| 17-item Hamilton Depression Rating Scale (HAMD-17) Total Score | 24.2 units on a scale STANDARD_DEVIATION 3.7 | 24.4 units on a scale STANDARD_DEVIATION 3.83 | 24.0 units on a scale STANDARD_DEVIATION 3.57 |
| Age Continuous | 47.9 years STANDARD_DEVIATION 13.1 | 47.4 years STANDARD_DEVIATION 12.72 | 48.3 years STANDARD_DEVIATION 13.48 |
| Clinical Global Impression-Major Depressive Disorder-Severity (CGI-MDD-S) Score | 4.6 units on a scale STANDARD_DEVIATION 0.62 | 4.6 units on a scale STANDARD_DEVIATION 0.64 | 4.6 units on a scale STANDARD_DEVIATION 0.59 |
| Euro Quality of Life-5 Dimensions Questionnaire (EQ-5D) Score EQ-5D UK Population-based Index Score | 0.37 units on a scale STANDARD_DEVIATION 0.303 | 0.34 units on a scale STANDARD_DEVIATION 0.312 | 0.40 units on a scale STANDARD_DEVIATION 0.291 |
| Euro Quality of Life-5 Dimensions Questionnaire (EQ-5D) Score Health State Score | 4.05 units on a scale STANDARD_DEVIATION 1.798 | 3.86 units on a scale STANDARD_DEVIATION 1.704 | 4.23 units on a scale STANDARD_DEVIATION 1.873 |
| Has the participant been hospitalized due to depression in the last 4 weeks Missing | 1 participants | 1 participants | 0 participants |
| Has the participant been hospitalized due to depression in the last 4 weeks No | 555 participants | 278 participants | 277 participants |
| Has the participant been hospitalized due to depression in the last 4 weeks Unknown | 1 participants | 0 participants | 1 participants |
| Has the participant been hospitalized due to depression in the last 4 weeks Yes | 9 participants | 5 participants | 4 participants |
| Number of visits to emergency room or equivalent facility due to depression in the last 4 weeks | 1.1 visits STANDARD_DEVIATION 0.4 | 1.1 visits STANDARD_DEVIATION 0.48 | 1.1 visits STANDARD_DEVIATION 0.27 |
| Number of visits to other specialists due to depression in the last 4 weeks | 1.8 visits STANDARD_DEVIATION 1.26 | 1.6 visits STANDARD_DEVIATION 0.98 | 2.0 visits STANDARD_DEVIATION 1.44 |
| Number of visits to primary healthcare provider due to depression in the last 4 weeks | 1.7 visits STANDARD_DEVIATION 1.03 | 1.8 visits STANDARD_DEVIATION 1.1 | 1.6 visits STANDARD_DEVIATION 0.95 |
| Number of work hours missed due to depression in the last 4 weeks | 88.6 hours STANDARD_DEVIATION 65.56 | 88.5 hours STANDARD_DEVIATION 67.05 | 88.8 hours STANDARD_DEVIATION 64.14 |
| Number of work hours missed in the last 4 weeks | 87.2 hours STANDARD_DEVIATION 64.67 | 87.5 hours STANDARD_DEVIATION 66.32 | 86.9 hours STANDARD_DEVIATION 63.09 |
| Number of work hours worked per week | 37.6 hours STANDARD_DEVIATION 8.94 | 37.2 hours STANDARD_DEVIATION 9.53 | 38.0 hours STANDARD_DEVIATION 8.3 |
| Quick Inventory of Depressive Symptomatology-Self Reported (QIDS16SR) Total Score | 16.5 units on a scale STANDARD_DEVIATION 3.63 | 16.7 units on a scale STANDARD_DEVIATION 3.43 | 16.4 units on a scale STANDARD_DEVIATION 3.82 |
| Race Black or African American | 4 participants | 2 participants | 2 participants |
| Race White | 562 participants | 282 participants | 280 participants |
| Region of Enrollment Denmark | 26 participants | 14 participants | 12 participants |
| Region of Enrollment France | 108 participants | 54 participants | 54 participants |
| Region of Enrollment Greece | 20 participants | 10 participants | 10 participants |
| Region of Enrollment Hungary | 12 participants | 6 participants | 6 participants |
| Region of Enrollment Italy | 39 participants | 20 participants | 19 participants |
| Region of Enrollment Netherlands | 9 participants | 4 participants | 5 participants |
| Region of Enrollment Romania | 36 participants | 18 participants | 18 participants |
| Region of Enrollment Slovenia | 10 participants | 4 participants | 6 participants |
| Region of Enrollment Spain | 144 participants | 73 participants | 71 participants |
| Region of Enrollment Sweden | 142 participants | 71 participants | 71 participants |
| Region of Enrollment Turkey | 20 participants | 10 participants | 10 participants |
| Sex: Female, Male Female | 393 Participants | 197 Participants | 196 Participants |
| Sex: Female, Male Male | 173 Participants | 87 Participants | 86 Participants |
| Sheehan Disability Scale (SDS) Total Score | 19.9 units on a scale STANDARD_DEVIATION 5.32 | 19.9 units on a scale STANDARD_DEVIATION 5.52 | 19.9 units on a scale STANDARD_DEVIATION 5.12 |
| Visual Analog Scale (VAS) Overall Pain Severity | 3.7 units on a scale STANDARD_DEVIATION 2.78 | 3.8 units on a scale STANDARD_DEVIATION 2.81 | 3.6 units on a scale STANDARD_DEVIATION 2.76 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 245 / 840 | 99 / 284 | 110 / 282 | 33 / 83 | 60 / 165 |
| serious Total, serious adverse events | 4 / 840 | 4 / 284 | 8 / 282 | 1 / 83 | 1 / 165 |
Outcome results
Primary
Estimated Probability of Not Reaching Confirmed Remission at 12 Weeks Based on the Survival Function for the Time to Confirmed Remission
Survival function is estimating the probability of participants not achieving confirmed remission. Confirmed remission is defined as a Hamilton Depression Rating Scale-17 Items (HAMD-17) Score of ≤ 7 that is maintained for two consecutive visits. The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe).
Time frame: Week 4 through Week 16
Population: Full Analysis Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Early Intervention | Estimated Probability of Not Reaching Confirmed Remission at 12 Weeks Based on the Survival Function for the Time to Confirmed Remission | 52 estimated probability (percent) |
| Delayed Intervention | Estimated Probability of Not Reaching Confirmed Remission at 12 Weeks Based on the Survival Function for the Time to Confirmed Remission | 59 estimated probability (percent) |
Comparison: Survival function estimated over a 12 week period (Week 4 through Week 16): analysis of early intervention versus delayed intervention strategiesp-value: 0.11695% CI: [-0.16, 0.02]Kaplan-Meier analysis
Primary
Estimated Probability of Not Reaching Confirmed Response at 12 Weeks Based on the Survival Function for the Time to Confirmed Response
Survival function is estimating the probability of participants not achieving confirmed response after 12 weeks. Confirmed response is defined as \>=50% change from baseline reduction in the Hamilton Depression Rating Scale-17 Items (HAMD-17). The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe).
Time frame: Week 4 through Week 16
Population: Full Analysis Population
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Early Intervention | Estimated Probability of Not Reaching Confirmed Response at 12 Weeks Based on the Survival Function for the Time to Confirmed Response | 28 estimated probability (percent) |
| Delayed Intervention | Estimated Probability of Not Reaching Confirmed Response at 12 Weeks Based on the Survival Function for the Time to Confirmed Response | 26 estimated probability (percent) |
Comparison: Survival function estimated over a 12 week period (Week 4 through Week 16): analysis of early intervention versus delayed intervention strategiesp-value: 0.65395% CI: [-0.06, 0.1]Kaplan Meier analysis
Primary
Time to Confirmed Remission by a Hamilton Depression Rating Scale-17 Items (HAMD-17) Score of ≤ 7 That is Maintained for Two Consecutive Visits
Time to confirmed remission is defined as the time from the day of study randomization (Visit 2) to the date of first observation of confirmed remission defined as a score on the HAMD-17 of ≤ 7 for 2 consecutive visits. The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe).
Time frame: Week 4 through Week 16
Population: Full Analysis Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Early Intervention | Time to Confirmed Remission by a Hamilton Depression Rating Scale-17 Items (HAMD-17) Score of ≤ 7 That is Maintained for Two Consecutive Visits | 12.9 weeks |
| Delayed Intervention | Time to Confirmed Remission by a Hamilton Depression Rating Scale-17 Items (HAMD-17) Score of ≤ 7 That is Maintained for Two Consecutive Visits | NA weeks |
Comparison: Kaplan-Meier estimates (weeks): analysis of early intervention versus delayed intervention strategiesp-value: 0.075Kaplan-Meier analysis
Primary
Time to Confirmed Response by ≥ 50% Change From Baseline Reduction in the Hamilton Depression Rating Scale-17 Items (HAMD-17)
Time to confirmed response is defined as the time from the day of study randomization (Visit 2) to the date of first observation of confirmed response defined as ≥ 50% baseline score reduction on the HAMD-17 for 2 consecutive visits. The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale, e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe).
Time frame: Week 4 through Week 16
Population: Full Analysis Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Early Intervention | Time to Confirmed Response by ≥ 50% Change From Baseline Reduction in the Hamilton Depression Rating Scale-17 Items (HAMD-17) | 6.4 weeks |
| Delayed Intervention | Time to Confirmed Response by ≥ 50% Change From Baseline Reduction in the Hamilton Depression Rating Scale-17 Items (HAMD-17) | 8.0 weeks |
Comparison: Kaplan-Meier Estimates (weeks): analysis of early intervention versus delayed intervention strategiesp-value: 0.213Kaplan-Meier Analysis
Secondary
Clinical Global Impressions of Severity (CGI-S) Scale
Measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill participants).
Time frame: Baseline, Week 4, Week 6, Week 8, Week 10, Week 12, Week 14, Week 16
Population: Full Analysis Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Early Intervention | Clinical Global Impressions of Severity (CGI-S) Scale | Baseline (n=282, 284) | 4.6 units on a scale | Standard Deviation 0.59 |
| Early Intervention | Clinical Global Impressions of Severity (CGI-S) Scale | Week 4 (n=281, 284) | 4.3 units on a scale | Standard Deviation 0.61 |
| Early Intervention | Clinical Global Impressions of Severity (CGI-S) Scale | Week 6 (n=271, 277) | 3.6 units on a scale | Standard Deviation 0.88 |
| Early Intervention | Clinical Global Impressions of Severity (CGI-S) Scale | Week 8 (n=254, 254) | 3.2 units on a scale | Standard Deviation 1.11 |
| Early Intervention | Clinical Global Impressions of Severity (CGI-S) Scale | Week 10 (n=231, 236) | 2.8 units on a scale | Standard Deviation 1.17 |
| Early Intervention | Clinical Global Impressions of Severity (CGI-S) Scale | Week 12 (n=203, 214) | 2.6 units on a scale | Standard Deviation 1.21 |
| Early Intervention | Clinical Global Impressions of Severity (CGI-S) Scale | Week 14 (n=184, 194) | 2.4 units on a scale | Standard Deviation 1.13 |
| Early Intervention | Clinical Global Impressions of Severity (CGI-S) Scale | Week 16 (n=178, 182) | 2.2 units on a scale | Standard Deviation 1.09 |
| Delayed Intervention | Clinical Global Impressions of Severity (CGI-S) Scale | Week 16 (n=178, 182) | 2.2 units on a scale | Standard Deviation 1.11 |
| Delayed Intervention | Clinical Global Impressions of Severity (CGI-S) Scale | Baseline (n=282, 284) | 4.6 units on a scale | Standard Deviation 0.64 |
| Delayed Intervention | Clinical Global Impressions of Severity (CGI-S) Scale | Week 10 (n=231, 236) | 2.9 units on a scale | Standard Deviation 1.22 |
| Delayed Intervention | Clinical Global Impressions of Severity (CGI-S) Scale | Week 4 (n=281, 284) | 4.3 units on a scale | Standard Deviation 0.66 |
| Delayed Intervention | Clinical Global Impressions of Severity (CGI-S) Scale | Week 14 (n=184, 194) | 2.5 units on a scale | Standard Deviation 1.17 |
| Delayed Intervention | Clinical Global Impressions of Severity (CGI-S) Scale | Week 6 (n=271, 277) | 3.7 units on a scale | Standard Deviation 0.97 |
| Delayed Intervention | Clinical Global Impressions of Severity (CGI-S) Scale | Week 12 (n=203, 214) | 2.7 units on a scale | Standard Deviation 1.2 |
| Delayed Intervention | Clinical Global Impressions of Severity (CGI-S) Scale | Week 8 (n=254, 254) | 3.3 units on a scale | Standard Deviation 1.15 |
Comparison: Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 6p-value: 0.62495% CI: [-0.22, 0.13]Mixed Models Analysis
Comparison: Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 8p-value: 0.20895% CI: [-0.29, 0.06]Mixed Models Analysis
Comparison: Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 10p-value: 0.04495% CI: [-0.37, 0]Mixed Models Analysis
Comparison: Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 12p-value: 0.08695% CI: [-0.35, 0.02]Mixed Models Analysis
Comparison: Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 14p-value: 0.18195% CI: [-0.33, 0.06]Mixed Models Analysis
Comparison: Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 16p-value: 0.99495% CI: [-0.2, 0.2]Mixed Models Analysis
Secondary
Euro Quality of Life Questionnaire-5 Dimensions (EQ-5D) Scale - Health State Score
The EQ-5D Health State Score is self-rated health on a vertical, visual analogue scale measured in centimeters (cm) and reported as units on a scale. Best imaginable health state = 10 cm and worst imaginable health state = 0 cm.
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16
Population: Full Analysis Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Early Intervention | Euro Quality of Life Questionnaire-5 Dimensions (EQ-5D) Scale - Health State Score | Week 4 (n=282, 280) | 4.9 units on a scale | Standard Deviation 1.76 |
| Early Intervention | Euro Quality of Life Questionnaire-5 Dimensions (EQ-5D) Scale - Health State Score | Week 12 (n=169, 177) | 5.9 units on a scale | Standard Deviation 1.96 |
| Early Intervention | Euro Quality of Life Questionnaire-5 Dimensions (EQ-5D) Scale - Health State Score | Week 8 (n=244, 237) | 5.7 units on a scale | Standard Deviation 1.88 |
| Early Intervention | Euro Quality of Life Questionnaire-5 Dimensions (EQ-5D) Scale - Health State Score | Week 16 (n=142, 153) | 6.5 units on a scale | Standard Deviation 1.9 |
| Early Intervention | Euro Quality of Life Questionnaire-5 Dimensions (EQ-5D) Scale - Health State Score | Baseline (n=281, 283) | 4.2 units on a scale | Standard Deviation 1.87 |
| Delayed Intervention | Euro Quality of Life Questionnaire-5 Dimensions (EQ-5D) Scale - Health State Score | Week 16 (n=142, 153) | 6.5 units on a scale | Standard Deviation 1.94 |
| Delayed Intervention | Euro Quality of Life Questionnaire-5 Dimensions (EQ-5D) Scale - Health State Score | Baseline (n=281, 283) | 3.9 units on a scale | Standard Deviation 1.7 |
| Delayed Intervention | Euro Quality of Life Questionnaire-5 Dimensions (EQ-5D) Scale - Health State Score | Week 4 (n=282, 280) | 4.5 units on a scale | Standard Deviation 1.62 |
| Delayed Intervention | Euro Quality of Life Questionnaire-5 Dimensions (EQ-5D) Scale - Health State Score | Week 8 (n=244, 237) | 5.4 units on a scale | Standard Deviation 1.94 |
| Delayed Intervention | Euro Quality of Life Questionnaire-5 Dimensions (EQ-5D) Scale - Health State Score | Week 12 (n=169, 177) | 5.8 units on a scale | Standard Deviation 1.98 |
Comparison: Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 8p-value: 0.40195% CI: [-0.19, 0.47]Mixed Models Analysis
Comparison: Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 12p-value: 0.61895% CI: [-0.27, 0.46]Mixed Models Analysis
Comparison: Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 16p-value: 0.85695% CI: [-0.43, 0.36]Mixed Models Analysis
Secondary
Euro Quality of Life Questionnaire-5 Dimensions (EQ-5D) Scale - United Kingdom (UK) Population Based Index Score
The EQ-5D is a generic, multidimensional, health-related, quality of life instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and mood. A single score between 1 and 3 is generated for each domain. For each participant, the outcome rating on the 5 domains will be mapped to a single index through an algorithm. The index ranges between 0 and 1, with the higher score indicating a better health state perceived by the participant.
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16
Population: Full Analysis Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Early Intervention | Euro Quality of Life Questionnaire-5 Dimensions (EQ-5D) Scale - United Kingdom (UK) Population Based Index Score | Week 4 (n=279, 282) | 0.5 units on a scale | Standard Deviation 0.3 |
| Early Intervention | Euro Quality of Life Questionnaire-5 Dimensions (EQ-5D) Scale - United Kingdom (UK) Population Based Index Score | Week 12 (n=168, 178) | 0.7 units on a scale | Standard Deviation 0.22 |
| Early Intervention | Euro Quality of Life Questionnaire-5 Dimensions (EQ-5D) Scale - United Kingdom (UK) Population Based Index Score | Week 8 (n=244, 238) | 0.7 units on a scale | Standard Deviation 0.25 |
| Early Intervention | Euro Quality of Life Questionnaire-5 Dimensions (EQ-5D) Scale - United Kingdom (UK) Population Based Index Score | Week 16 (n=143, 153) | 0.7 units on a scale | Standard Deviation 0.24 |
| Early Intervention | Euro Quality of Life Questionnaire-5 Dimensions (EQ-5D) Scale - United Kingdom (UK) Population Based Index Score | Baseline (n=279, 282) | 0.4 units on a scale | Standard Deviation 0.29 |
| Delayed Intervention | Euro Quality of Life Questionnaire-5 Dimensions (EQ-5D) Scale - United Kingdom (UK) Population Based Index Score | Week 16 (n=143, 153) | 0.7 units on a scale | Standard Deviation 0.24 |
| Delayed Intervention | Euro Quality of Life Questionnaire-5 Dimensions (EQ-5D) Scale - United Kingdom (UK) Population Based Index Score | Baseline (n=279, 282) | 0.3 units on a scale | Standard Deviation 0.31 |
| Delayed Intervention | Euro Quality of Life Questionnaire-5 Dimensions (EQ-5D) Scale - United Kingdom (UK) Population Based Index Score | Week 4 (n=279, 282) | 0.5 units on a scale | Standard Deviation 0.32 |
| Delayed Intervention | Euro Quality of Life Questionnaire-5 Dimensions (EQ-5D) Scale - United Kingdom (UK) Population Based Index Score | Week 8 (n=244, 238) | 0.6 units on a scale | Standard Deviation 0.3 |
| Delayed Intervention | Euro Quality of Life Questionnaire-5 Dimensions (EQ-5D) Scale - United Kingdom (UK) Population Based Index Score | Week 12 (n=168, 178) | 0.6 units on a scale | Standard Deviation 0.28 |
Comparison: Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 8p-value: 0.02195% CI: [-0.1, -0.01]Mixed Models Analysis
Comparison: Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 12p-value: 0.07195% CI: [-0.09, 0]Mixed Models Analysis
Comparison: Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 16p-value: 0.79295% CI: [-0.05, 0.06]Mixed Models Analysis
Secondary
Number of Participants With Adverse Events (AEs)
The list of AEs is located in the Reported Adverse Event module.
Time frame: Baseline through Week 16
Population: Full Analysis Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Early Intervention | Number of Participants With Adverse Events (AEs) | Number of participants with adverse events | 112 participants |
| Early Intervention | Number of Participants With Adverse Events (AEs) | Number of participants with serious adverse events | 8 participants |
| Delayed Intervention | Number of Participants With Adverse Events (AEs) | Number of participants with adverse events | 101 participants |
| Delayed Intervention | Number of Participants With Adverse Events (AEs) | Number of participants with serious adverse events | 4 participants |
Secondary
Resource Utilisation - Has the Participant Been Hospitalized Due to Depression in the Last 4 Weeks - Number of Participants With a Yes Response
Time frame: Week 4, Week 8, Week 12, Week 16
Population: Full Analysis Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Early Intervention | Resource Utilisation - Has the Participant Been Hospitalized Due to Depression in the Last 4 Weeks - Number of Participants With a Yes Response | Week 4 | 1 participants |
| Early Intervention | Resource Utilisation - Has the Participant Been Hospitalized Due to Depression in the Last 4 Weeks - Number of Participants With a Yes Response | Week 8 | 0 participants |
| Early Intervention | Resource Utilisation - Has the Participant Been Hospitalized Due to Depression in the Last 4 Weeks - Number of Participants With a Yes Response | Week 12 | 0 participants |
| Early Intervention | Resource Utilisation - Has the Participant Been Hospitalized Due to Depression in the Last 4 Weeks - Number of Participants With a Yes Response | Week 16 | 0 participants |
| Delayed Intervention | Resource Utilisation - Has the Participant Been Hospitalized Due to Depression in the Last 4 Weeks - Number of Participants With a Yes Response | Week 16 | 0 participants |
| Delayed Intervention | Resource Utilisation - Has the Participant Been Hospitalized Due to Depression in the Last 4 Weeks - Number of Participants With a Yes Response | Week 4 | 0 participants |
| Delayed Intervention | Resource Utilisation - Has the Participant Been Hospitalized Due to Depression in the Last 4 Weeks - Number of Participants With a Yes Response | Week 12 | 0 participants |
| Delayed Intervention | Resource Utilisation - Has the Participant Been Hospitalized Due to Depression in the Last 4 Weeks - Number of Participants With a Yes Response | Week 8 | 0 participants |
Secondary
Resource Utilisation - Number of Hours Worked Per Week
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16
Population: Full Analysis Population, which included all randomized participants with at least 1 post-randomization assessment available after Week 4. For efficacy analyses, participants were included in the analysis if they had a baseline and a post-baseline (after Week 4) value of the variable in question.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Early Intervention | Resource Utilisation - Number of Hours Worked Per Week | Week 12 (n=119, 115) | 37.7 Hours | Standard Deviation 7.4 |
| Early Intervention | Resource Utilisation - Number of Hours Worked Per Week | Week 4 (n=153, 159) | 37.7 Hours | Standard Deviation 11.61 |
| Early Intervention | Resource Utilisation - Number of Hours Worked Per Week | Week 16 (n=96, 96) | 37.2 Hours | Standard Deviation 7.8 |
| Early Intervention | Resource Utilisation - Number of Hours Worked Per Week | Week 8 (n=136, 141) | 37.9 Hours | Standard Deviation 9.08 |
| Delayed Intervention | Resource Utilisation - Number of Hours Worked Per Week | Week 16 (n=96, 96) | 38.0 Hours | Standard Deviation 14.74 |
| Delayed Intervention | Resource Utilisation - Number of Hours Worked Per Week | Week 4 (n=153, 159) | 38.6 Hours | Standard Deviation 13.33 |
| Delayed Intervention | Resource Utilisation - Number of Hours Worked Per Week | Week 12 (n=119, 115) | 38.1 Hours | Standard Deviation 13.72 |
| Delayed Intervention | Resource Utilisation - Number of Hours Worked Per Week | Week 8 (n=136, 141) | 37.7 Hours | Standard Deviation 8.42 |
Secondary
Resource Utilisation - Number of Visits to Other Specialists Due to Depression in the Last 4 Weeks
Time frame: Week 4, Week 8, Week 12, Week 16
Population: Full Analysis Population, which included all randomized participants with at least 1 post-randomization assessment available after Week 4. For efficacy analyses, participants were included in the analysis if they had a baseline and a post-baseline (after Week 4) value of the variable in question.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Early Intervention | Resource Utilisation - Number of Visits to Other Specialists Due to Depression in the Last 4 Weeks | Week 4 (n=25, 16) | 2.2 Visits | Standard Deviation 2.05 |
| Early Intervention | Resource Utilisation - Number of Visits to Other Specialists Due to Depression in the Last 4 Weeks | Week 8 (n=8, 8) | 1.6 Visits | Standard Deviation 0.74 |
| Early Intervention | Resource Utilisation - Number of Visits to Other Specialists Due to Depression in the Last 4 Weeks | Week 12 (n=3, 2) | 1.7 Visits | Standard Deviation 1.15 |
| Early Intervention | Resource Utilisation - Number of Visits to Other Specialists Due to Depression in the Last 4 Weeks | Week 16 (n=2, 1) | 2.0 Visits | Standard Deviation 0 |
| Delayed Intervention | Resource Utilisation - Number of Visits to Other Specialists Due to Depression in the Last 4 Weeks | Week 16 (n=2, 1) | 3.0 Visits | — |
| Delayed Intervention | Resource Utilisation - Number of Visits to Other Specialists Due to Depression in the Last 4 Weeks | Week 4 (n=25, 16) | 1.7 Visits | Standard Deviation 0.87 |
| Delayed Intervention | Resource Utilisation - Number of Visits to Other Specialists Due to Depression in the Last 4 Weeks | Week 12 (n=3, 2) | 1.0 Visits | Standard Deviation 0 |
| Delayed Intervention | Resource Utilisation - Number of Visits to Other Specialists Due to Depression in the Last 4 Weeks | Week 8 (n=8, 8) | 1.9 Visits | Standard Deviation 1.13 |
Secondary
Resource Utilisation - Number of Visits to Primary Healthcare Provider Due to Depression in the Last 4 Weeks
Time frame: Week 4, Week 8, Week 12, Week 16
Population: Full Analysis Population, which included all randomized participants with at least 1 post-randomization assessment available after Week 4. For efficacy analyses, participants were included in the analysis if they had a baseline and a post-baseline (after Week 4) value of the variable in question.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Early Intervention | Resource Utilisation - Number of Visits to Primary Healthcare Provider Due to Depression in the Last 4 Weeks | Week 4 (n=36, 55) | 1.5 Visits | Standard Deviation 1 |
| Early Intervention | Resource Utilisation - Number of Visits to Primary Healthcare Provider Due to Depression in the Last 4 Weeks | Week 8 (n=14, 22) | 1.1 Visits | Standard Deviation 0.27 |
| Early Intervention | Resource Utilisation - Number of Visits to Primary Healthcare Provider Due to Depression in the Last 4 Weeks | Week 12 (n=8, 12) | 1.3 Visits | Standard Deviation 0.46 |
| Early Intervention | Resource Utilisation - Number of Visits to Primary Healthcare Provider Due to Depression in the Last 4 Weeks | Week 16 (n=4, 7) | 2.0 Visits | Standard Deviation 2 |
| Delayed Intervention | Resource Utilisation - Number of Visits to Primary Healthcare Provider Due to Depression in the Last 4 Weeks | Week 16 (n=4, 7) | 1.6 Visits | Standard Deviation 1.13 |
| Delayed Intervention | Resource Utilisation - Number of Visits to Primary Healthcare Provider Due to Depression in the Last 4 Weeks | Week 4 (n=36, 55) | 1.6 Visits | Standard Deviation 1.04 |
| Delayed Intervention | Resource Utilisation - Number of Visits to Primary Healthcare Provider Due to Depression in the Last 4 Weeks | Week 12 (n=8, 12) | 1.6 Visits | Standard Deviation 1 |
| Delayed Intervention | Resource Utilisation - Number of Visits to Primary Healthcare Provider Due to Depression in the Last 4 Weeks | Week 8 (n=14, 22) | 1.7 Visits | Standard Deviation 1.13 |
Secondary
Resource Utilisation - Number of Work Hours Missed Due to Depression in the Last 4 Weeks
Only those participants who missed at least 1 hour of work due to depression were included.
Time frame: Week 4, Week 8, Week 12, Week 16
Population: Full Analysis Population, which included all randomized participants with at least 1 post-randomization assessment available after Week 4. For efficacy analyses, participants were included in the analysis if they had a baseline and a post-baseline (after Week 4) value of the variable in question.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Early Intervention | Resource Utilisation - Number of Work Hours Missed Due to Depression in the Last 4 Weeks | Week 4 (n=70, 86) | 90.6 Hours | Standard Deviation 64.98 |
| Early Intervention | Resource Utilisation - Number of Work Hours Missed Due to Depression in the Last 4 Weeks | Week 8 (n=47, 61) | 98.5 Hours | Standard Deviation 65.34 |
| Early Intervention | Resource Utilisation - Number of Work Hours Missed Due to Depression in the Last 4 Weeks | Week 12 (n=31, 52) | 98.7 Hours | Standard Deviation 64.32 |
| Early Intervention | Resource Utilisation - Number of Work Hours Missed Due to Depression in the Last 4 Weeks | Week 16 (n=24, 38) | 91.9 Hours | Standard Deviation 64.99 |
| Delayed Intervention | Resource Utilisation - Number of Work Hours Missed Due to Depression in the Last 4 Weeks | Week 16 (n=24, 38) | 126.0 Hours | Standard Deviation 63.4 |
| Delayed Intervention | Resource Utilisation - Number of Work Hours Missed Due to Depression in the Last 4 Weeks | Week 4 (n=70, 86) | 95.1 Hours | Standard Deviation 67.9 |
| Delayed Intervention | Resource Utilisation - Number of Work Hours Missed Due to Depression in the Last 4 Weeks | Week 12 (n=31, 52) | 111.4 Hours | Standard Deviation 66.42 |
| Delayed Intervention | Resource Utilisation - Number of Work Hours Missed Due to Depression in the Last 4 Weeks | Week 8 (n=47, 61) | 109.7 Hours | Standard Deviation 68.08 |
Secondary
Resource Utilisation - Number of Work Hours Missed in the Last 4 Weeks
Only those participants who missed at least 1 hour of work were included.
Time frame: Week 4, Week 8, Week 12, Week 16
Population: Full Analysis Population, which included all randomized participants with at least 1 post-randomization assessment available after Week 4. For efficacy analyses, participants were included in the analysis if they had a baseline and a post-baseline (after Week 4) value of the variable in question.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Early Intervention | Resource Utilisation - Number of Work Hours Missed in the Last 4 Weeks | Week 4 (n=73, 89) | 88.6 Hours | Standard Deviation 64.3 |
| Early Intervention | Resource Utilisation - Number of Work Hours Missed in the Last 4 Weeks | Week 8 (n=54, 67) | 92.5 Hours | Standard Deviation 66.12 |
| Early Intervention | Resource Utilisation - Number of Work Hours Missed in the Last 4 Weeks | Week 12 (n=38, 56) | 85.0 Hours | Standard Deviation 65.73 |
| Early Intervention | Resource Utilisation - Number of Work Hours Missed in the Last 4 Weeks | Week 16 (n=25, 39) | 91.5 Hours | Standard Deviation 63.49 |
| Delayed Intervention | Resource Utilisation - Number of Work Hours Missed in the Last 4 Weeks | Week 16 (n=25, 39) | 126.4 Hours | Standard Deviation 63.64 |
| Delayed Intervention | Resource Utilisation - Number of Work Hours Missed in the Last 4 Weeks | Week 4 (n=73, 89) | 95.0 Hours | Standard Deviation 67.4 |
| Delayed Intervention | Resource Utilisation - Number of Work Hours Missed in the Last 4 Weeks | Week 12 (n=38, 56) | 104.5 Hours | Standard Deviation 68.72 |
| Delayed Intervention | Resource Utilisation - Number of Work Hours Missed in the Last 4 Weeks | Week 8 (n=54, 67) | 102.3 Hours | Standard Deviation 69.38 |
Secondary
Sheehan Disability Scale (SDS) Normal Functioning Total Score
The SDS is completed by the participant and is used to assess the effect of the participant's symptoms on their work/social/family life. Total scores range from 0 to 30 with higher values indicating greater disruption in the participant's work/social/family life.
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16
Population: Full Analysis Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Early Intervention | Sheehan Disability Scale (SDS) Normal Functioning Total Score | Week 4 (n=215, 215) | 16.9 units on a scale | Standard Deviation 6.36 |
| Early Intervention | Sheehan Disability Scale (SDS) Normal Functioning Total Score | Week 12 (n=140, 144) | 12.1 units on a scale | Standard Deviation 6.84 |
| Early Intervention | Sheehan Disability Scale (SDS) Normal Functioning Total Score | Week 8 (n=186, 188) | 13.5 units on a scale | Standard Deviation 6.5 |
| Early Intervention | Sheehan Disability Scale (SDS) Normal Functioning Total Score | Week 16 (n=113, 121) | 10.3 units on a scale | Standard Deviation 7.27 |
| Early Intervention | Sheehan Disability Scale (SDS) Normal Functioning Total Score | Baseline (n=216, 217) | 19.9 units on a scale | Standard Deviation 5.12 |
| Delayed Intervention | Sheehan Disability Scale (SDS) Normal Functioning Total Score | Week 16 (n=113, 121) | 10.2 units on a scale | Standard Deviation 6.97 |
| Delayed Intervention | Sheehan Disability Scale (SDS) Normal Functioning Total Score | Baseline (n=216, 217) | 19.9 units on a scale | Standard Deviation 5.52 |
| Delayed Intervention | Sheehan Disability Scale (SDS) Normal Functioning Total Score | Week 4 (n=215, 215) | 17.5 units on a scale | Standard Deviation 6.11 |
| Delayed Intervention | Sheehan Disability Scale (SDS) Normal Functioning Total Score | Week 8 (n=186, 188) | 14.0 units on a scale | Standard Deviation 6.79 |
| Delayed Intervention | Sheehan Disability Scale (SDS) Normal Functioning Total Score | Week 12 (n=140, 144) | 13.2 units on a scale | Standard Deviation 7.51 |
Comparison: Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 8p-value: 0.59795% CI: [-1.74, 1]Mixed Models Analysis
Comparison: Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 12p-value: 0.3695% CI: [-2.13, 0.78]Mixed Models Analysis
Comparison: Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 16p-value: 0.93795% CI: [-1.52, 1.65]Mixed Models Analysis
Secondary
Time to Confirmed Remission as Defined by a 16-Item Quick Inventory of Depressive Symptomatology Self Report (QIDS16SR) Score of ≤ 5 That is Maintained for Two Consecutive Visits.
Time to confirmed remission is defined as the time from the day of study randomization (Visit 2) to the date of first observation of confirmed remission. A 16-item participant-rated measure of depressive symptomatology. The total score ranges from 0 to 27 with higher scores indicative of greater severity.
Time frame: Week 4 through Week 16
Population: Full Analysis Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Early Intervention | Time to Confirmed Remission as Defined by a 16-Item Quick Inventory of Depressive Symptomatology Self Report (QIDS16SR) Score of ≤ 5 That is Maintained for Two Consecutive Visits. | NA weeks |
| Delayed Intervention | Time to Confirmed Remission as Defined by a 16-Item Quick Inventory of Depressive Symptomatology Self Report (QIDS16SR) Score of ≤ 5 That is Maintained for Two Consecutive Visits. | NA weeks |
Comparison: Analysis of early intervention strategy versus delayed intervention strategyp-value: 0.597Kaplan-Meier analysis
Secondary
Time to Confirmed Response as Defined by ≥ 50% Reduction From Baseline Reduction in the 16-Item Quick Inventory of Depressive Symptomatology Self Report (QIDS16SR) That is Reported for Two Consecutive Visits
Time to confirmed response is defined as the time from the day of study randomization (Visit 2) to the date of first observation of confirmed response. QIDS16SR is a 16-item participant-rated measure of depressive symptomatology. The total score ranges from 0 to 27 with higher scores indicative of greater severity.
Time frame: Week 4 through Week 16
Population: Full Analysis Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Early Intervention | Time to Confirmed Response as Defined by ≥ 50% Reduction From Baseline Reduction in the 16-Item Quick Inventory of Depressive Symptomatology Self Report (QIDS16SR) That is Reported for Two Consecutive Visits | 6.0 weeks |
| Delayed Intervention | Time to Confirmed Response as Defined by ≥ 50% Reduction From Baseline Reduction in the 16-Item Quick Inventory of Depressive Symptomatology Self Report (QIDS16SR) That is Reported for Two Consecutive Visits | 6.9 weeks |
Comparison: Analysis of early intervention strategy versus delayed intervention strategyp-value: 0.947Kaplan Meier analysis
Secondary
Visual Analog Scale (VAS) - Overall Pain Severity
VAS for pain consists of 6 questions that assess overall pain, headache, back pain, shoulder pain, pain interference with daily activities, and pain while awake. Participant rates pain on a 10 centimeter (cm) line between two anchors (0= no pain and 10=very severe pain).
Time frame: Baseline, Week 4, Week 6, Week 8, Week 10, Week 12, Week 14, Week 16
Population: Full Analysis Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Early Intervention | Visual Analog Scale (VAS) - Overall Pain Severity | Baseline (n=282, 284) | 3.6 units on a scale | Standard Deviation 2.76 |
| Early Intervention | Visual Analog Scale (VAS) - Overall Pain Severity | Week 4 (n=281, 283) | 3.0 units on a scale | Standard Deviation 2.54 |
| Early Intervention | Visual Analog Scale (VAS) - Overall Pain Severity | Week 6 (n=270, 271) | 2.6 units on a scale | Standard Deviation 2.41 |
| Early Intervention | Visual Analog Scale (VAS) - Overall Pain Severity | Week 8 (n=245, 241) | 2.4 units on a scale | Standard Deviation 2.53 |
| Early Intervention | Visual Analog Scale (VAS) - Overall Pain Severity | Week 10 (n=207, 204) | 2.4 units on a scale | Standard Deviation 2.48 |
| Early Intervention | Visual Analog Scale (VAS) - Overall Pain Severity | Week 12 (n=170, 181) | 2.1 units on a scale | Standard Deviation 2.42 |
| Early Intervention | Visual Analog Scale (VAS) - Overall Pain Severity | Week 14 (n=151, 152) | 2.0 units on a scale | Standard Deviation 2.35 |
| Early Intervention | Visual Analog Scale (VAS) - Overall Pain Severity | Week 16 (n=143, 152) | 2.0 units on a scale | Standard Deviation 2.32 |
| Delayed Intervention | Visual Analog Scale (VAS) - Overall Pain Severity | Week 16 (n=143, 152) | 2.3 units on a scale | Standard Deviation 2.55 |
| Delayed Intervention | Visual Analog Scale (VAS) - Overall Pain Severity | Baseline (n=282, 284) | 3.8 units on a scale | Standard Deviation 2.81 |
| Delayed Intervention | Visual Analog Scale (VAS) - Overall Pain Severity | Week 10 (n=207, 204) | 2.7 units on a scale | Standard Deviation 2.6 |
| Delayed Intervention | Visual Analog Scale (VAS) - Overall Pain Severity | Week 4 (n=281, 283) | 3.5 units on a scale | Standard Deviation 2.77 |
| Delayed Intervention | Visual Analog Scale (VAS) - Overall Pain Severity | Week 14 (n=151, 152) | 2.5 units on a scale | Standard Deviation 2.54 |
| Delayed Intervention | Visual Analog Scale (VAS) - Overall Pain Severity | Week 6 (n=270, 271) | 3.3 units on a scale | Standard Deviation 2.85 |
| Delayed Intervention | Visual Analog Scale (VAS) - Overall Pain Severity | Week 12 (n=170, 181) | 2.6 units on a scale | Standard Deviation 2.66 |
| Delayed Intervention | Visual Analog Scale (VAS) - Overall Pain Severity | Week 8 (n=245, 241) | 3.0 units on a scale | Standard Deviation 2.7 |
Comparison: Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 6p-value: 0.00195% CI: [-0.98, -0.25]Mixed Models Analysis
Comparison: Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 8p-value: 0.0195% CI: [-0.87, -0.12]Mixed Models Analysis
Comparison: Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 10p-value: 0.44595% CI: [-0.55, 0.24]Mixed Models Analysis
Comparison: Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 12p-value: 0.16995% CI: [-0.71, 0.12]Mixed Models Analysis
Comparison: Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 14p-value: 0.39395% CI: [-0.63, 0.25]Mixed Models Analysis
Comparison: Repeated Measurements Analysis: Early Intervention versus Delayed Intervention Strategy at Week 16p-value: 0.5195% CI: [-0.61, 0.3]Mixed Models Analysis