Major Depressive Disorder, Treatment Resistant Depression
Conditions
Keywords
Depression, MDD, TRD
Brief summary
The primary objective of the study is to evaluate the efficacy of Quetiapine extended release (XR) in combination with an selective serotonin reuptake inhibitor (SSRI) or Venlafaxine versus Lithium in combination with an selective serotonin reuptake inhibitor or Venlafaxine versus Quetiapine extended release monotherapy in subjects with treatment resistant depression as assessed by the changes from randomisation to week 6 in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. As an independent objective, the primary objective will also be evaluated in two subgroups of patients: (1) patients who were resistant to two previous antidepressant therapies and (2) in the subgroup of patients with one previous failure.
Detailed description
The secondary objectives of the study are to compare the effects of the three different treatment regimen as assessed by the following variables and, if applicable, by their changes from randomisation to week 6 (end of study). Additionally the time of onset of therapeutic effect will be assessed by evaluating efficacy data after the first four days (Day 4) of treatment as well as after the first week of treatment (Day 8). These analyses will also be performed in the subgroups of patients with 2 failed previous antidepressants and patients with 1 failure.
Interventions
DRUGQuetiapine XR
300 mg once daily (od)
DRUGLithium carbonate
900 mg once daily (od)
DRUGSSRI/Venlafaxine
SSRI - doses within label, Venlafaxine dose up to 225 mg/day
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Documented clinical diagnosis as confirmed by the M.I.N.I. meeting criteria from the Diagnostic and Statistical Manual of Mental disorders, 4th Edition (DSM-IV) for any of the following:296.2x MDD, Single Episode296.3x MDD, Recurrent Episode * Current episode of depression present, at least 42 days prior to enrolment but not more than 18 months * MADRS-Score ≥ 25 at enrolment and randomisation
Exclusion criteria
* Patients with a DSM-IV Axis I disorder other than MDD within 6 months of randomisation * Patients with a diagnosis of DSM-IV Axis II disorder which has a major impact on the patient's current psychiatric status * Patients who, in the investigator's judgment pose a current serious suicidal or homicidal risk, or have made a suicide attempt within the past 6 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Depressive Symptoms Between Randomisation and Week 6 Measured by Change in Montgomery Asberg Depression Rating Scale (MADRS) Total Score (Per Protocol Analysis Set) | 6 weeks treatment | Change in LS mean total Montgomery Asberg Depression Rating Scale (MADRS) score from randomisation to end-of-treatment (week 6) (Scale 0-60), lower score indicates a better health status. |
| Change in Depressive Symptoms Between Randomisation and Week 6 Measured by Change in Montgomery Asberg Depression Rating Scale (MADRS) Total Score (Modified Intention to Treat Analysis Set) | 6 weeks of treatment | Change in LS mean total Montgomery Asberg Depression Rating Scale (MADRS) score from randomisation to end-of-treatment (week 6) (Scale 0-60), lower score indicates a better health status. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤10, Patients With Two Previous Treatment Failure | 6 weeks of treatment | Number of patients in remission with two previous treatment failure and with total Montgomery Asberg Depression Rating Scale (MADRS) score ≤10. MADRS scale has range from 0 to 60, where the lower score indicates the better health status. |
| Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤8 | 6 weeks of treatment | Number of patients in remission with total Montgomery Asberg Depression Rating Scale (MADRS) score ≤8. MADRS scale has range from 0 to 60, where the lower score indicates the better health status. |
| Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤12 | 6 weeks of treatment | Number of patients in remission with total Montgomery Asberg Depression Rating Scale (MADRS) score ≤12. MADRS scale has range from 0 to 60, where the lower score indicates the better health status. |
| Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, All Patients | 6 week of treatments | Response rate at end of study measured as number of patients with Montgomery Asberg Depression Rating Scale (MADRS) with total score reduction ≥ 50% compared to baseline, the higher number of patients the better |
| Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, Patients With One Previous Treatment Failure | 6 weeks of treatment | Response rate at end of study measured as number of patients with Montgomery Asberg Depression Rating Scale (MADRS) with total score reduction ≥ 50% compared to baseline, the higher number of patients the better |
| Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, Patients With Two Previous Treatment Failure | 6 weeks of treatment | Response rate at end of study measured as number of patients with Montgomery Asberg Depression Rating Scale (MADRS) with total score reduction ≥ 50% compared to baseline, the higher number of patients the better |
| Responder: Clinical Global Impression Improvement (CGI-I) Item 2, All Patients | 6 weeks of treatment | Change in global improvement measured by Clinical Global Impression Improvement (CGI-I). Scale from 1-4, where lower value shows a larger improvement. |
| Responder: Clinical Global Impression Improvement (CGI)-I Item 2, Patients With One Previous Treatment Failure | 6 weeks of treatment | Change in global improvement measured by Clinical Global Impression Improvement (CGI-I). Scale from 1-4, where a lower value shows a larger improvement. |
| Responder: Clinical Global Impression Improvement (CGI-I) Item 2, Patients With Two Previous Treatment Failure | 6 weeks of treatment | Change in global improvement measured by Clinical Global Impression Improvement (CGI-I). Scale from 1-4, where a lower value shows a larger improvement. |
| Change in Clinical Global Impression Scale (CGI-S), All Patients | 6 weeks of treatment | Change in severity of illness measured by Clinical Global Impression Scale (CGI-S). Scale form 1-7, where a lower value shows a larger improvement. |
| Change in Clinical Global Impression Scale (CGI-S), Patients With One Previous Treatment Failure | 6 weeks of treatment | Change in severity of illness measured by Clinical Global Impression Scale (CGI-S). Scale from 1-7, where a lower value shows a larger improvement. |
| Change in Clinical Global Impression Scale (CGI-S), Patients With Two Previous Treatment Failure | 6 weeks of treatment | Change in severity of illness measured by Clinical Global Impression Scale (CGI-S). Scale from 1-7, where a lower value shows a larger improvement. |
| Change in Beck Depression Inventory (BDI) | 6 weeks of treatment | Self-rating assessment of depressive symptoms using Beck Depression Inventory (BDI). Scale from 0-63, where a lower value shows a larger improvement. |
| Depression Remission; Montgomery-Asberg Depression Rating Scale MADRS ≤10, All Patients | 6 weeks of treatment | Number of patients in remission, with total Montgomery Asberg Depression Rating Scale (MADRS) score ≤10. MADRS scale has range from 0 to 60, where the lower score indicates the better health status. |
| Change in Anxiety Measured by Visual Analog Scale (VAS) | 6 weeks of treatment | Self-rating assessment of anxiety using a visual analogue scale (VAS). Scale from 0-100, where a lower value shows a larger improvement. |
| Change in Anxiety Measured by State-Trait Anxiety Inventory (STAI), State Anxiety Inventory | 6 weeks of treatment | Self-rating assessment of anxiety measured by STAI, state anxiety inventory (Scale 20-80, where a lower value shows a larger improvement) |
| Change in Anxiety Measured by STAI, Trait Anxiety Inventory | 6 weeks of treatment | Self-rating assessment of anxiety measured by State-Trait Anxiety Inventory (STAI), trait anxiety inventory (Scale 20-80, where a lower value shows a larger improvement) |
| Change in Sleep Quality Measured by Montgomery Asberg Depression Rating Scale (MADRS), Item 4 | 6 weeks of treatment | Sleeping quality measured by Montgomery-Asberg Depression Rating Scale (MADRS) item 4 (reduced sleep) (Scale 0-6, where a lower value shows a larger improvement) |
| Change in Sleep Quality Measured by Pittsburgh Sleep Quality Index (PSQI) | 6 weeks of treatment | Self-rated sleeping quality measured by PSQI (Scale 0-21, subscales 0-3, 18 questions, where a lower value shows a larger improvement) |
| Change in Quality of Life Measured by Short-form Health Survey (SF-36), Mental Component | 6 weeks of treatment | Self rating assessment of quality in life using SF-36, mental component (Scale 0-100, where a higher value shows a larger improvement) |
| Change in Quality of Life Measured by Short-form Health Survey (SF-36), Physical Component | 6 weeks of treatment | Self rating assessment of quality in life using SF-36, physical component (Scale 0-100, where a higher value shows a larger improvement) |
| Change in Quality of Life Measured by Health Questionnaire EQ-5D as Utility | 6 weeks of treatment | Self rating assessment of quality in life using EQ-5D utility (Scale 0-100, where a higher value shows a larger improvement) |
| Change in Work Productivity and Activity Impairment: General Health (WPAI:GH) | 6 weeks of treatment | Self rating assessment of working productivity using WPAI:GH (Scale 0 to number of hours worked during a week multiplied with the salary in Euro, a lower value shows a larger improvement) |
| Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, All Patients | 6 weeks of treatment | The physician has evaluated the therapeutic effect and the side effect combined at end of study. Patients with a 'marked/moderate' therapeutic effect and 'None/Do Not Significantly Interfere' side effect has been added. The higher values show more patients with a treatment effect without any side-effect. The range is from 0 patients to the maximum number of patients in the treatment arm (225, 229 or 221). |
| Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, Patients With One Previous Treatment Failure | 6 weeks of treatment | The physician has evaluated the therapeutic effect and the side effect combined at end of study. Patients with a 'marked/moderate' therapeutic effect and 'None/Do Not Significantly Interfere' side effect has been added. The higher values show more patients with a treatment effect without any side-effect. The range is from 0 patients to the maximum number of patients in the treatment arm. |
| Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, Patients With Two Previous Treatment Failures | 6 week of treatments | The physician has evaluated the therapeutic effect and the side effect combined at end of study. Patients with a 'marked/moderate' therapeutic effect and 'None/Do Not Significantly Interfere' side effect has been added. The higher values show more patients with a treatment effect without any side-effect. The range is from 0 patients to the maximum number of patients in the treatment arm. |
| Change in Pain, Measured by Visual Analog Scale (VAS) | 6 weeks of treatment | Self-rating assessment of pain using a visual analogue scale (VAS). Scale from 0-100, where a lower value shows a larger improvement. |
| Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤10, Patients With One Previous Treatment Failure | 6 weeks of treatment | Number of patients in remission with one previous treatment failure and with total Montgomery Asberg Depression Rating Scale (MADRS) score ≤10. MADRS scale has range from 0 to 60, where the lower score indicates the better health status. |
Countries
Australia, Austria, Belgium, Bulgaria, Denmark, Germany, Hungary, Italy, Portugal, Romania, Slovakia, Spain, United Kingdom
Participant flow
Recruitment details
This was a 3 arm, open-label randomised, rater blinded, parallel group study comparing quetiapine XR monotherapy and augmentation with lithium augmentation in patients with treatment resistant depression, Recruitment period 6 November 2008 to 19 June 2009
Pre-assignment details
At visit 1 and 2 (randomisation) the patients should have a Montgomery-Asberg Depression Rating Scale (MADRS) total score above or equal to 25
Participants by arm
| Arm | Count |
|---|---|
| Quetiapine XR Mono Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od) | 225 |
| Add-on Quetiapine XR Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od) | 229 |
| Add-on Lithium Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od) | 221 |
| Total | 675 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 28 | 23 | 18 |
| Overall Study | Eligibility criteria not fulfilled | 2 | 5 | 1 |
| Overall Study | Lost to Follow-up | 1 | 1 | 4 |
| Overall Study | Other | 6 | 0 | 5 |
| Overall Study | Safety reasons | 0 | 0 | 2 |
| Overall Study | Severe non-compliance to the protocol | 3 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 9 | 6 | 17 |
Baseline characteristics
| Characteristic | Quetiapine XR Mono | Add-on Quetiapine XR | Add-on Lithium | Total |
|---|---|---|---|---|
| Age Continuous | 47 years | 47 years | 47 years | 47 years |
| Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Diagnose code 296.2x Major Depressive Disorder (MD | 50 Participants | 36 Participants | 41 Participants | 127 Participants |
| Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Diagnose code 296.3x MDD, Recurrent | 175 Participants | 193 Participants | 180 Participants | 548 Participants |
| Montgomery-Asberg Depression Rating Scale (MADRS) total score | 33.74 Units on a scale STANDARD_DEVIATION 5.6 | 33.15 Units on a scale STANDARD_DEVIATION 5.34 | 32.91 Units on a scale STANDARD_DEVIATION 5.2 | 33.32 Units on a scale STANDARD_DEVIATION 5.4 |
| Sex: Female, Male Female | 152 Participants | 162 Participants | 152 Participants | 466 Participants |
| Sex: Female, Male Male | 73 Participants | 67 Participants | 69 Participants | 209 Participants |
| Weight | 75.3 kg STANDARD_DEVIATION 17.2 | 75.2 kg STANDARD_DEVIATION 17 | 76.4 kg STANDARD_DEVIATION 16.1 | 75.8 kg STANDARD_DEVIATION 16.65 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 93 / 228 | 90 / 231 | 41 / 229 |
| serious Total, serious adverse events | 5 / 228 | 5 / 231 | 2 / 229 |
Outcome results
Primary
Change in Depressive Symptoms Between Randomisation and Week 6 Measured by Change in Montgomery Asberg Depression Rating Scale (MADRS) Total Score (Modified Intention to Treat Analysis Set)
Change in LS mean total Montgomery Asberg Depression Rating Scale (MADRS) score from randomisation to end-of-treatment (week 6) (Scale 0-60), lower score indicates a better health status.
Time frame: 6 weeks of treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR Mono | Change in Depressive Symptoms Between Randomisation and Week 6 Measured by Change in Montgomery Asberg Depression Rating Scale (MADRS) Total Score (Modified Intention to Treat Analysis Set) | -13.9 scores on a scale | Standard Error 0.806 |
| Add-on Quetiapine XR | Change in Depressive Symptoms Between Randomisation and Week 6 Measured by Change in Montgomery Asberg Depression Rating Scale (MADRS) Total Score (Modified Intention to Treat Analysis Set) | -15.1 scores on a scale | Standard Error 0.797 |
| Add-on Lithium | Change in Depressive Symptoms Between Randomisation and Week 6 Measured by Change in Montgomery Asberg Depression Rating Scale (MADRS) Total Score (Modified Intention to Treat Analysis Set) | -13.3 scores on a scale | Standard Error 0.801 |
Comparison: The null hypothesis was that the add-on quetiapine XR treatment was not different to the add-on lithium treatment. The power calculation was done for the primary non-inferior analysis. This superiority analysis was only done if the non-inferior analysis was successful.p-value: 0.0489ANCOVA
Comparison: The null hypothesis was that the quetiapine XR mono treatment was not different from the add-on lithium treatment. The power calculation was done for the primary non-inferior analysis. This superiority analysis was only done if the non-inferior analysis was successful.p-value: 0.4368ANCOVA
Primary
Change in Depressive Symptoms Between Randomisation and Week 6 Measured by Change in Montgomery Asberg Depression Rating Scale (MADRS) Total Score (Per Protocol Analysis Set)
Change in LS mean total Montgomery Asberg Depression Rating Scale (MADRS) score from randomisation to end-of-treatment (week 6) (Scale 0-60), lower score indicates a better health status.
Time frame: 6 weeks treatment
Population: Analysis was 'per protocol'. Exclusion reason from analysis: Violation of exclusion/inclusion criteria; Non-compliance regarding prohibited concomitant medication, Total unavailability of MADRS score after randomization, Patient not treated with any dose of study drug after randomization, Non-compliance regarding titration to 300 mg quetiapine/d.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR Mono | Change in Depressive Symptoms Between Randomisation and Week 6 Measured by Change in Montgomery Asberg Depression Rating Scale (MADRS) Total Score (Per Protocol Analysis Set) | -16.2 scores on a scale | Standard Error 0.843 |
| Add-on Quetiapine XR | Change in Depressive Symptoms Between Randomisation and Week 6 Measured by Change in Montgomery Asberg Depression Rating Scale (MADRS) Total Score (Per Protocol Analysis Set) | -17.2 scores on a scale | Standard Error 0.826 |
| Add-on Lithium | Change in Depressive Symptoms Between Randomisation and Week 6 Measured by Change in Montgomery Asberg Depression Rating Scale (MADRS) Total Score (Per Protocol Analysis Set) | -14.9 scores on a scale | Standard Error 0.97 |
Comparison: Add-on quetiapine XR was tested versus add-on lithium for non-inferiority. The null hypothesis was that the add-on quetiapine treatment was non-inferior to add-on lithium.97.5% CI: [-4.6, -0.05]ANCOVA
Comparison: Quetiapine XR mono was tested versus add-on lithium for non-inferiority. The null hypothesis was that the quetiapine XR mono treatment was non-inferior to add-on lithium.97.5% CI: [-3.24, 1.312]ANCOVA
Secondary
Change in Anxiety Measured by STAI, Trait Anxiety Inventory
Self-rating assessment of anxiety measured by State-Trait Anxiety Inventory (STAI), trait anxiety inventory (Scale 20-80, where a lower value shows a larger improvement)
Time frame: 6 weeks of treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR Mono | Change in Anxiety Measured by STAI, Trait Anxiety Inventory | -1.01 Scores on a scale | Standard Error 0.331 |
| Add-on Quetiapine XR | Change in Anxiety Measured by STAI, Trait Anxiety Inventory | -1.36 Scores on a scale | Standard Error 0.328 |
| Add-on Lithium | Change in Anxiety Measured by STAI, Trait Anxiety Inventory | -1.39 Scores on a scale | Standard Error 0.331 |
Secondary
Change in Anxiety Measured by State-Trait Anxiety Inventory (STAI), State Anxiety Inventory
Self-rating assessment of anxiety measured by STAI, state anxiety inventory (Scale 20-80, where a lower value shows a larger improvement)
Time frame: 6 weeks of treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR Mono | Change in Anxiety Measured by State-Trait Anxiety Inventory (STAI), State Anxiety Inventory | -0.62 Scores on a scale | Standard Error 0.347 |
| Add-on Quetiapine XR | Change in Anxiety Measured by State-Trait Anxiety Inventory (STAI), State Anxiety Inventory | 0.014 Scores on a scale | Standard Error 0.344 |
| Add-on Lithium | Change in Anxiety Measured by State-Trait Anxiety Inventory (STAI), State Anxiety Inventory | -0.87 Scores on a scale | Standard Error 0.35 |
Secondary
Change in Anxiety Measured by Visual Analog Scale (VAS)
Self-rating assessment of anxiety using a visual analogue scale (VAS). Scale from 0-100, where a lower value shows a larger improvement.
Time frame: 6 weeks of treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR Mono | Change in Anxiety Measured by Visual Analog Scale (VAS) | -21.2 scores on a scale | Standard Error 1.972 |
| Add-on Quetiapine XR | Change in Anxiety Measured by Visual Analog Scale (VAS) | -23.4 scores on a scale | Standard Error 1.947 |
| Add-on Lithium | Change in Anxiety Measured by Visual Analog Scale (VAS) | -20.6 scores on a scale | Standard Error 1.952 |
Secondary
Change in Beck Depression Inventory (BDI)
Self-rating assessment of depressive symptoms using Beck Depression Inventory (BDI). Scale from 0-63, where a lower value shows a larger improvement.
Time frame: 6 weeks of treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR Mono | Change in Beck Depression Inventory (BDI) | -11.7 scores on a scale | Standard Error 0.926 |
| Add-on Quetiapine XR | Change in Beck Depression Inventory (BDI) | -13.5 scores on a scale | Standard Error 0.921 |
| Add-on Lithium | Change in Beck Depression Inventory (BDI) | -12.2 scores on a scale | Standard Error 0.922 |
Secondary
Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, All Patients
The physician has evaluated the therapeutic effect and the side effect combined at end of study. Patients with a 'marked/moderate' therapeutic effect and 'None/Do Not Significantly Interfere' side effect has been added. The higher values show more patients with a treatment effect without any side-effect. The range is from 0 patients to the maximum number of patients in the treatment arm (225, 229 or 221).
Time frame: 6 weeks of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine XR Mono | Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, All Patients | 135 Participants |
| Add-on Quetiapine XR | Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, All Patients | 146 Participants |
| Add-on Lithium | Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, All Patients | 131 Participants |
Secondary
Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, Patients With One Previous Treatment Failure
The physician has evaluated the therapeutic effect and the side effect combined at end of study. Patients with a 'marked/moderate' therapeutic effect and 'None/Do Not Significantly Interfere' side effect has been added. The higher values show more patients with a treatment effect without any side-effect. The range is from 0 patients to the maximum number of patients in the treatment arm.
Time frame: 6 weeks of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine XR Mono | Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, Patients With One Previous Treatment Failure | 67 Participants |
| Add-on Quetiapine XR | Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, Patients With One Previous Treatment Failure | 75 Participants |
| Add-on Lithium | Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, Patients With One Previous Treatment Failure | 69 Participants |
Secondary
Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, Patients With Two Previous Treatment Failures
The physician has evaluated the therapeutic effect and the side effect combined at end of study. Patients with a 'marked/moderate' therapeutic effect and 'None/Do Not Significantly Interfere' side effect has been added. The higher values show more patients with a treatment effect without any side-effect. The range is from 0 patients to the maximum number of patients in the treatment arm.
Time frame: 6 week of treatments
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine XR Mono | Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, Patients With Two Previous Treatment Failures | 68 Participants |
| Add-on Quetiapine XR | Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, Patients With Two Previous Treatment Failures | 71 Participants |
| Add-on Lithium | Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, Patients With Two Previous Treatment Failures | 62 Participants |
Secondary
Change in Clinical Global Impression Scale (CGI-S), All Patients
Change in severity of illness measured by Clinical Global Impression Scale (CGI-S). Scale form 1-7, where a lower value shows a larger improvement.
Time frame: 6 weeks of treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR Mono | Change in Clinical Global Impression Scale (CGI-S), All Patients | -1.43 scores on a scale | Standard Error 0.101 |
| Add-on Quetiapine XR | Change in Clinical Global Impression Scale (CGI-S), All Patients | -1.65 scores on a scale | Standard Error 0.099 |
| Add-on Lithium | Change in Clinical Global Impression Scale (CGI-S), All Patients | -1.49 scores on a scale | Standard Error 0.1 |
Secondary
Change in Clinical Global Impression Scale (CGI-S), Patients With One Previous Treatment Failure
Change in severity of illness measured by Clinical Global Impression Scale (CGI-S). Scale from 1-7, where a lower value shows a larger improvement.
Time frame: 6 weeks of treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR Mono | Change in Clinical Global Impression Scale (CGI-S), Patients With One Previous Treatment Failure | -1.45 scores on a scale | Standard Error 0.133 |
| Add-on Quetiapine XR | Change in Clinical Global Impression Scale (CGI-S), Patients With One Previous Treatment Failure | -1.82 scores on a scale | Standard Error 0.13 |
| Add-on Lithium | Change in Clinical Global Impression Scale (CGI-S), Patients With One Previous Treatment Failure | -1.59 scores on a scale | Standard Error 0.13 |
Secondary
Change in Clinical Global Impression Scale (CGI-S), Patients With Two Previous Treatment Failure
Change in severity of illness measured by Clinical Global Impression Scale (CGI-S). Scale from 1-7, where a lower value shows a larger improvement.
Time frame: 6 weeks of treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR Mono | Change in Clinical Global Impression Scale (CGI-S), Patients With Two Previous Treatment Failure | -1.52 scores on a scale | Standard Error 0.133 |
| Add-on Quetiapine XR | Change in Clinical Global Impression Scale (CGI-S), Patients With Two Previous Treatment Failure | -1.55 scores on a scale | Standard Error 0.131 |
| Add-on Lithium | Change in Clinical Global Impression Scale (CGI-S), Patients With Two Previous Treatment Failure | -1.45 scores on a scale | Standard Error 0.135 |
Secondary
Change in Pain, Measured by Visual Analog Scale (VAS)
Self-rating assessment of pain using a visual analogue scale (VAS). Scale from 0-100, where a lower value shows a larger improvement.
Time frame: 6 weeks of treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR Mono | Change in Pain, Measured by Visual Analog Scale (VAS) | -9.47 scores on a scale | Standard Error 1.695 |
| Add-on Quetiapine XR | Change in Pain, Measured by Visual Analog Scale (VAS) | -8.03 scores on a scale | Standard Error 1.681 |
| Add-on Lithium | Change in Pain, Measured by Visual Analog Scale (VAS) | -8.3 scores on a scale | Standard Error 1.682 |
Secondary
Change in Quality of Life Measured by Health Questionnaire EQ-5D as Utility
Self rating assessment of quality in life using EQ-5D utility (Scale 0-100, where a higher value shows a larger improvement)
Time frame: 6 weeks of treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR Mono | Change in Quality of Life Measured by Health Questionnaire EQ-5D as Utility | 0.184 Scores on a scale | Standard Error 0.023 |
| Add-on Quetiapine XR | Change in Quality of Life Measured by Health Questionnaire EQ-5D as Utility | 0.224 Scores on a scale | Standard Error 0.023 |
| Add-on Lithium | Change in Quality of Life Measured by Health Questionnaire EQ-5D as Utility | 0.208 Scores on a scale | Standard Error 0.023 |
Secondary
Change in Quality of Life Measured by Short-form Health Survey (SF-36), Mental Component
Self rating assessment of quality in life using SF-36, mental component (Scale 0-100, where a higher value shows a larger improvement)
Time frame: 6 weeks of treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR Mono | Change in Quality of Life Measured by Short-form Health Survey (SF-36), Mental Component | 9.59 Scores on a scale | Standard Error 0.929 |
| Add-on Quetiapine XR | Change in Quality of Life Measured by Short-form Health Survey (SF-36), Mental Component | 10.77 Scores on a scale | Standard Error 0.925 |
| Add-on Lithium | Change in Quality of Life Measured by Short-form Health Survey (SF-36), Mental Component | 9.66 Scores on a scale | Standard Error 0.932 |
Secondary
Change in Quality of Life Measured by Short-form Health Survey (SF-36), Physical Component
Self rating assessment of quality in life using SF-36, physical component (Scale 0-100, where a higher value shows a larger improvement)
Time frame: 6 weeks of treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR Mono | Change in Quality of Life Measured by Short-form Health Survey (SF-36), Physical Component | 5.224 Scores on a scale | Standard Error 0.811 |
| Add-on Quetiapine XR | Change in Quality of Life Measured by Short-form Health Survey (SF-36), Physical Component | 5.065 Scores on a scale | Standard Error 0.813 |
| Add-on Lithium | Change in Quality of Life Measured by Short-form Health Survey (SF-36), Physical Component | 4.566 Scores on a scale | Standard Error 0.817 |
Secondary
Change in Sleep Quality Measured by Montgomery Asberg Depression Rating Scale (MADRS), Item 4
Sleeping quality measured by Montgomery-Asberg Depression Rating Scale (MADRS) item 4 (reduced sleep) (Scale 0-6, where a lower value shows a larger improvement)
Time frame: 6 weeks of treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR Mono | Change in Sleep Quality Measured by Montgomery Asberg Depression Rating Scale (MADRS), Item 4 | -2.2 MADRS item 4 score | Standard Error 0.108 |
| Add-on Quetiapine XR | Change in Sleep Quality Measured by Montgomery Asberg Depression Rating Scale (MADRS), Item 4 | -2.4 MADRS item 4 score | Standard Error 0.107 |
| Add-on Lithium | Change in Sleep Quality Measured by Montgomery Asberg Depression Rating Scale (MADRS), Item 4 | -1.63 MADRS item 4 score | Standard Error 0.108 |
Secondary
Change in Sleep Quality Measured by Pittsburgh Sleep Quality Index (PSQI)
Self-rated sleeping quality measured by PSQI (Scale 0-21, subscales 0-3, 18 questions, where a lower value shows a larger improvement)
Time frame: 6 weeks of treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR Mono | Change in Sleep Quality Measured by Pittsburgh Sleep Quality Index (PSQI) | -4.77 Scores on a scale | Standard Error 0.36 |
| Add-on Quetiapine XR | Change in Sleep Quality Measured by Pittsburgh Sleep Quality Index (PSQI) | -4.96 Scores on a scale | Standard Error 0.358 |
| Add-on Lithium | Change in Sleep Quality Measured by Pittsburgh Sleep Quality Index (PSQI) | -3.51 Scores on a scale | Standard Error 0.364 |
Secondary
Change in Work Productivity and Activity Impairment: General Health (WPAI:GH)
Self rating assessment of working productivity using WPAI:GH (Scale 0 to number of hours worked during a week multiplied with the salary in Euro, a lower value shows a larger improvement)
Time frame: 6 weeks of treatment
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR Mono | Change in Work Productivity and Activity Impairment: General Health (WPAI:GH) | -233 Scores on a scale | Standard Error 0.023 |
| Add-on Quetiapine XR | Change in Work Productivity and Activity Impairment: General Health (WPAI:GH) | -185 Scores on a scale | Standard Error 0.023 |
| Add-on Lithium | Change in Work Productivity and Activity Impairment: General Health (WPAI:GH) | -299 Scores on a scale | Standard Error 0.023 |
Secondary
Depression Remission; Montgomery-Asberg Depression Rating Scale MADRS ≤10, All Patients
Number of patients in remission, with total Montgomery Asberg Depression Rating Scale (MADRS) score ≤10. MADRS scale has range from 0 to 60, where the lower score indicates the better health status.
Time frame: 6 weeks of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine XR Mono | Depression Remission; Montgomery-Asberg Depression Rating Scale MADRS ≤10, All Patients | 53 Participants |
| Add-on Quetiapine XR | Depression Remission; Montgomery-Asberg Depression Rating Scale MADRS ≤10, All Patients | 73 Participants |
| Add-on Lithium | Depression Remission; Montgomery-Asberg Depression Rating Scale MADRS ≤10, All Patients | 60 Participants |
Secondary
Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤10, Patients With One Previous Treatment Failure
Number of patients in remission with one previous treatment failure and with total Montgomery Asberg Depression Rating Scale (MADRS) score ≤10. MADRS scale has range from 0 to 60, where the lower score indicates the better health status.
Time frame: 6 weeks of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine XR Mono | Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤10, Patients With One Previous Treatment Failure | 22 Participants |
| Add-on Quetiapine XR | Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤10, Patients With One Previous Treatment Failure | 42 Participants |
| Add-on Lithium | Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤10, Patients With One Previous Treatment Failure | 31 Participants |
Secondary
Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤10, Patients With Two Previous Treatment Failure
Number of patients in remission with two previous treatment failure and with total Montgomery Asberg Depression Rating Scale (MADRS) score ≤10. MADRS scale has range from 0 to 60, where the lower score indicates the better health status.
Time frame: 6 weeks of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine XR Mono | Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤10, Patients With Two Previous Treatment Failure | 31 Participants |
| Add-on Quetiapine XR | Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤10, Patients With Two Previous Treatment Failure | 31 Participants |
| Add-on Lithium | Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤10, Patients With Two Previous Treatment Failure | 29 Participants |
Secondary
Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤12
Number of patients in remission with total Montgomery Asberg Depression Rating Scale (MADRS) score ≤12. MADRS scale has range from 0 to 60, where the lower score indicates the better health status.
Time frame: 6 weeks of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine XR Mono | Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤12 | 67 Participants |
| Add-on Quetiapine XR | Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤12 | 89 Participants |
| Add-on Lithium | Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤12 | 73 Participants |
Secondary
Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤8
Number of patients in remission with total Montgomery Asberg Depression Rating Scale (MADRS) score ≤8. MADRS scale has range from 0 to 60, where the lower score indicates the better health status.
Time frame: 6 weeks of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine XR Mono | Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤8 | 35 Participants |
| Add-on Quetiapine XR | Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤8 | 58 Participants |
| Add-on Lithium | Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤8 | 45 Participants |
Secondary
Responder: Clinical Global Impression Improvement (CGI-I) Item 2, All Patients
Change in global improvement measured by Clinical Global Impression Improvement (CGI-I). Scale from 1-4, where lower value shows a larger improvement.
Time frame: 6 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR Mono | Responder: Clinical Global Impression Improvement (CGI-I) Item 2, All Patients | -1.54 scores on a scale | Standard Deviation 1.24 |
| Add-on Quetiapine XR | Responder: Clinical Global Impression Improvement (CGI-I) Item 2, All Patients | -1.85 scores on a scale | Standard Deviation 1.34 |
| Add-on Lithium | Responder: Clinical Global Impression Improvement (CGI-I) Item 2, All Patients | -1.58 scores on a scale | Standard Deviation 1.32 |
Secondary
Responder: Clinical Global Impression Improvement (CGI)-I Item 2, Patients With One Previous Treatment Failure
Change in global improvement measured by Clinical Global Impression Improvement (CGI-I). Scale from 1-4, where a lower value shows a larger improvement.
Time frame: 6 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR Mono | Responder: Clinical Global Impression Improvement (CGI)-I Item 2, Patients With One Previous Treatment Failure | -1.42 scores on a scale | Standard Deviation 1.17 |
| Add-on Quetiapine XR | Responder: Clinical Global Impression Improvement (CGI)-I Item 2, Patients With One Previous Treatment Failure | -1.91 scores on a scale | Standard Deviation 1.31 |
| Add-on Lithium | Responder: Clinical Global Impression Improvement (CGI)-I Item 2, Patients With One Previous Treatment Failure | -1.62 scores on a scale | Standard Deviation 1.27 |
Secondary
Responder: Clinical Global Impression Improvement (CGI-I) Item 2, Patients With Two Previous Treatment Failure
Change in global improvement measured by Clinical Global Impression Improvement (CGI-I). Scale from 1-4, where a lower value shows a larger improvement.
Time frame: 6 weeks of treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine XR Mono | Responder: Clinical Global Impression Improvement (CGI-I) Item 2, Patients With Two Previous Treatment Failure | -1.67 scores on a scale | Standard Deviation 1.3 |
| Add-on Quetiapine XR | Responder: Clinical Global Impression Improvement (CGI-I) Item 2, Patients With Two Previous Treatment Failure | -1.79 scores on a scale | Standard Deviation 1.36 |
| Add-on Lithium | Responder: Clinical Global Impression Improvement (CGI-I) Item 2, Patients With Two Previous Treatment Failure | -1.54 scores on a scale | Standard Deviation 1.38 |
Secondary
Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, All Patients
Response rate at end of study measured as number of patients with Montgomery Asberg Depression Rating Scale (MADRS) with total score reduction ≥ 50% compared to baseline, the higher number of patients the better
Time frame: 6 week of treatments
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine XR Mono | Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, All Patients | 114 Participants |
| Add-on Quetiapine XR | Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, All Patients | 120 Participants |
| Add-on Lithium | Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, All Patients | 102 Participants |
Secondary
Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, Patients With One Previous Treatment Failure
Response rate at end of study measured as number of patients with Montgomery Asberg Depression Rating Scale (MADRS) with total score reduction ≥ 50% compared to baseline, the higher number of patients the better
Time frame: 6 weeks of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine XR Mono | Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, Patients With One Previous Treatment Failure | 54 Participants |
| Add-on Quetiapine XR | Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, Patients With One Previous Treatment Failure | 65 Participants |
| Add-on Lithium | Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, Patients With One Previous Treatment Failure | 53 Participants |
Secondary
Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, Patients With Two Previous Treatment Failure
Response rate at end of study measured as number of patients with Montgomery Asberg Depression Rating Scale (MADRS) with total score reduction ≥ 50% compared to baseline, the higher number of patients the better
Time frame: 6 weeks of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Quetiapine XR Mono | Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, Patients With Two Previous Treatment Failure | 60 Participants |
| Add-on Quetiapine XR | Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, Patients With Two Previous Treatment Failure | 55 Participants |
| Add-on Lithium | Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, Patients With Two Previous Treatment Failure | 49 Participants |