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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
688
300 mg once daily (od)
900 mg once daily (od)
SSRI - doses within label, Venlafaxine dose up to 225 mg/day
Research Site
Garran, Australian Capital Territory, Australia
Research Site
Brisbane, Queensland, Australia
Research Site
Everton Park, Queensland, Australia
Research Site
Townsville, Queensland, Australia
Research Site
Gilberton, South Australia, Australia
Research Site
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Clayton, Victoria, Australia
Research Site
Frankston, Victoria, Australia
Research Site
Heidelberg, Victoria, Australia
Research Site
Malvern, Victoria, Australia
Research Site
Prahran, Victoria, Australia
...and 96 more locations