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Comparing Quetiapine XR Monotherapy and Augmentation With Lithium Augmentation in TRD Patients (RUBY)

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ClinicalTrials.gov Identifier: NCT00789854
Recruitment Status : Completed
First Posted : November 13, 2008
Results First Posted : May 23, 2012
Last Update Posted : May 23, 2012
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Major Depressive Disorder
Treatment Resistant Depression
Interventions Drug: Quetiapine XR
Drug: Lithium carbonate
Drug: SSRI/Venlafaxine
Enrollment 688
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
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od) Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od) Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Period Title: Overall Study
Started 228 231 229
Completed 179 196 182
Not Completed 49 35 47
Reason Not Completed
Adverse Event             28             23             18
Lost to Follow-up             1             1             4
Withdrawal by Subject             9             6             17
Eligibility criteria not fulfilled             2             5             1
Severe non-compliance to the protocol             3             0             0
Safety reasons             0             0             2
Other             6             0             5
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium Total
Hide Arm/Group Description Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od) Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od) Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od) Total of all reporting groups
Overall Number of Baseline Participants 225 229 221 675
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous   [1] 
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 225 participants 229 participants 221 participants 675 participants
47
(20 to 65)
47
(20 to 67)
47
(19 to 67)
47
(19 to 67)
[1]
Measure Description: Baseline characteristics are presented using the ITT population (Quetiapine XR mono 225 participants, Add-on Quetiapine XR 229 participants and Add-on Lithium 221 participants) and not all randomized patients
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 225 participants 229 participants 221 participants 675 participants
Female
152
  67.6%
162
  70.7%
152
  68.8%
466
  69.0%
Male
73
  32.4%
67
  29.3%
69
  31.2%
209
  31.0%
[1]
Measure Description: Baseline characteristics are presented using the ITT population (Quetiapine XR mono 225 participants, Add-on Quetiapine XR 229 participants and Add-on Lithium 221 participants) and not all randomized patients
Diagnostic and Statistical Manual of Mental Disorders (DSM-IV)  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 225 participants 229 participants 221 participants 675 participants
Diagnose code 296.2x Major Depressive Disorder (MD 50 36 41 127
Diagnose code 296.3x MDD, Recurrent 175 193 180 548
Montgomery-Asberg Depression Rating Scale (MADRS) total score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 225 participants 229 participants 221 participants 675 participants
33.74  (5.6) 33.15  (5.34) 32.91  (5.2) 33.32  (5.4)
[1]
Measure Description: Units on a scale from 0 to 60. Lower score indicates a better health status.
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 225 participants 229 participants 221 participants 675 participants
75.3  (17.2) 75.2  (17) 76.4  (16.1) 75.8  (16.65)
1.Primary Outcome
Title 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)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 180 183 109
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
-16.2  (0.843) -17.2  (0.826) -14.9  (0.97)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Add-on Quetiapine XR, Add-on Lithium
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments

The non-inferiority margin for differences was set to 3 units in the MADRS total score.

A power set to 80% and using a Bonferroni-adjusted one-sided alpha* = alpha/3 = 0.0083 yields a planned sample size of 192 patients per study group. With a drop out of 4% a total of 600 randomized patients were required to obtain 192 efficacy evaluable patients per treatment group.

Statistical Test of Hypothesis P-Value [Not Specified]
Comments The CI is for comparing add-on quetiapine versus add-on Lithium. The CI = confidence interval was adjusted for multiple comparisons. The -0.05 value should have been +3 or above to fail to reject the null hypothesis.
Method ANCOVA
Comments Non-inferiority between add-on quetiapine XR and add-on lithium was shown in the Per Protocol analysis set.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -2.322
Confidence Interval 97.5%
-4.6 to -0.05
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Quetiapine XR Mono, Add-on Lithium
Comments 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.
Type of Statistical Test Non-Inferiority or Equivalence
Comments

The non-inferiority margin for differences was set to 3 units in the MADRS total score.

A power set to 80% and using a Bonferroni-adjusted one-sided alpha* = alpha/3 = 0.0083 yields a planned sample size of 192 patients per study group. With a drop out of 4% a total of 600 randomized patients were required to obtain 192 efficacy evaluable patients per treatment group.

Statistical Test of Hypothesis P-Value [Not Specified]
Comments The CI is for comparing quetiapine XR mono versus add-on Lithium. The CI = confidence interval was adjusted for multiple comparisons. The 1.312 value should have been +3 or above to fail to reject the null hypothesis.
Method ANCOVA
Comments Non-inferiority between quetiapine XR mono and add-on lithium was shown in the Per Protocol analysis set.
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value -1.639
Confidence Interval 97.5%
-3.24 to 1.312
Estimation Comments [Not Specified]
2.Primary Outcome
Title 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)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 225 229 221
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
-13.9  (0.806) -15.1  (0.797) -13.3  (0.801)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Add-on Quetiapine XR, Add-on Lithium
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0489
Comments Adjustment for multiplicity was done, alpha = 0.025
Method ANCOVA
Comments Superiority testing of primary outcome showed no significant difference in the Modified Intention To Treat (ITT) population
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Quetiapine XR Mono, Add-on Lithium
Comments 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.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4368
Comments Adjustment for multiplicity was done, alpha = 0.025
Method ANCOVA
Comments Superiority testing of primary outcome showed no significant difference in the Modified Intention To Treat (ITT) population
3.Secondary Outcome
Title Depression Remission; Montgomery-Asberg Depression Rating Scale MADRS ≤10, All Patients
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 225 229 221
Measure Type: Number
Unit of Measure: Participants
53 73 60
4.Secondary Outcome
Title Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤10, Patients With One Previous Treatment Failure
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 114 117 114
Measure Type: Number
Unit of Measure: Participants
22 42 31
5.Secondary Outcome
Title Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤10, Patients With Two Previous Treatment Failure
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 114 114 115
Measure Type: Number
Unit of Measure: Participants
31 31 29
6.Secondary Outcome
Title Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤8
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 225 229 221
Measure Type: Number
Unit of Measure: Participants
35 58 45
7.Secondary Outcome
Title Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤12
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 225 229 221
Measure Type: Number
Unit of Measure: Participants
67 89 73
8.Secondary Outcome
Title Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, All Patients
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 225 229 221
Measure Type: Number
Unit of Measure: Participants
114 120 102
9.Secondary Outcome
Title Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, Patients With One Previous Treatment Failure
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 114 117 114
Measure Type: Number
Unit of Measure: Participants
54 65 53
10.Secondary Outcome
Title Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, Patients With Two Previous Treatment Failure
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 114 114 115
Measure Type: Number
Unit of Measure: Participants
60 55 49
11.Secondary Outcome
Title Responder: Clinical Global Impression Improvement (CGI-I) Item 2, All Patients
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 224 229 220
Mean (Standard Deviation)
Unit of Measure: scores on a scale
-1.54  (1.24) -1.85  (1.34) -1.58  (1.32)
12.Secondary Outcome
Title Responder: Clinical Global Impression Improvement (CGI)-I Item 2, Patients With One Previous Treatment Failure
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 113 115 111
Mean (Standard Deviation)
Unit of Measure: scores on a scale
-1.42  (1.17) -1.91  (1.31) -1.62  (1.27)
13.Secondary Outcome
Title Responder: Clinical Global Impression Improvement (CGI-I) Item 2, Patients With Two Previous Treatment Failure
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 111 114 109
Mean (Standard Deviation)
Unit of Measure: scores on a scale
-1.67  (1.30) -1.79  (1.36) -1.54  (1.38)
14.Secondary Outcome
Title Change in Clinical Global Impression Scale (CGI-S), All Patients
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 224 229 220
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
-1.43  (0.101) -1.65  (0.099) -1.49  (0.1)
15.Secondary Outcome
Title Change in Clinical Global Impression Scale (CGI-S), Patients With One Previous Treatment Failure
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 113 115 111
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
-1.45  (0.133) -1.82  (0.13) -1.59  (0.13)
16.Secondary Outcome
Title Change in Clinical Global Impression Scale (CGI-S), Patients With Two Previous Treatment Failure
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 111 114 109
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
-1.52  (0.133) -1.55  (0.131) -1.45  (0.135)
17.Secondary Outcome
Title Change in Beck Depression Inventory (BDI)
Time Frame 6 weeks of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 213 212 205
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
-11.7  (0.926) -13.5  (0.921) -12.2  (0.922)
18.Secondary Outcome
Title Change in Pain, Measured by Visual Analog Scale (VAS)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 221 222 218
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
-9.47  (1.695) -8.03  (1.681) -8.3  (1.682)
19.Secondary Outcome
Title Change in Anxiety Measured by Visual Analog Scale (VAS)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 219 224 218
Least Squares Mean (Standard Error)
Unit of Measure: scores on a scale
-21.2  (1.972) -23.4  (1.947) -20.6  (1.952)
20.Secondary Outcome
Title Change in Anxiety Measured by State-Trait Anxiety Inventory (STAI), State Anxiety Inventory
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 223 227 217
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
-0.62  (0.347) 0.014  (0.344) -0.87  (0.35)
21.Secondary Outcome
Title Change in Anxiety Measured by STAI, Trait Anxiety Inventory
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 220 220 214
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
-1.01  (0.331) -1.36  (0.328) -1.39  (0.331)
22.Secondary Outcome
Title Change in Sleep Quality Measured by Montgomery Asberg Depression Rating Scale (MADRS), Item 4
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 225 229 221
Least Squares Mean (Standard Error)
Unit of Measure: MADRS item 4 score
-2.2  (0.108) -2.4  (0.107) -1.63  (0.108)
23.Secondary Outcome
Title Change in Sleep Quality Measured by Pittsburgh Sleep Quality Index (PSQI)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 200 196 185
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
-4.77  (0.36) -4.96  (0.358) -3.51  (0.364)
24.Secondary Outcome
Title Change in Quality of Life Measured by Short-form Health Survey (SF-36), Mental Component
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 178 171 174
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
9.59  (0.929) 10.77  (0.925) 9.66  (0.932)
25.Secondary Outcome
Title Change in Quality of Life Measured by Short-form Health Survey (SF-36), Physical Component
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 178 171 174
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
5.224  (0.811) 5.065  (0.813) 4.566  (0.817)
26.Secondary Outcome
Title Change in Quality of Life Measured by Health Questionnaire EQ-5D as Utility
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 220 220 215
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
0.184  (0.023) 0.224  (0.023) 0.208  (0.023)
27.Secondary Outcome
Title Change in Work Productivity and Activity Impairment: General Health (WPAI:GH)
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 31 39 25
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
-233  (0.023) -185  (0.023) -299  (0.023)
28.Secondary Outcome
Title Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, All Patients
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 225 229 221
Measure Type: Number
Unit of Measure: Participants
135 146 131
29.Secondary Outcome
Title Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, Patients With One Previous Treatment Failure
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 113 115 111
Measure Type: Number
Unit of Measure: Participants
67 75 69
30.Secondary Outcome
Title Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, Patients With Two Previous Treatment Failures
Hide Description 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
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description:
Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)
Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Number of Participants Analyzed 112 114 110
Measure Type: Number
Unit of Measure: Participants
68 71 62
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Hide Arm/Group Description Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od) Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od) Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
All-Cause Mortality
Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/228 (2.19%)   5/231 (2.16%)   2/229 (0.87%) 
Gastrointestinal disorders       
Diarrhoea  1  0/228 (0.00%)  1/231 (0.43%)  0/229 (0.00%) 
Hepatobiliary disorders       
Cholelithiasis  1  0/228 (0.00%)  0/231 (0.00%)  1/229 (0.44%) 
Injury, poisoning and procedural complications       
Overdose  1  1/228 (0.44%)  0/231 (0.00%)  0/229 (0.00%) 
Psychiatric disorders       
Depression  1  0/228 (0.00%)  3/231 (1.30%)  1/229 (0.44%) 
Affective Disorder  1  1/228 (0.44%)  0/231 (0.00%)  0/229 (0.00%) 
Psychotic Disorder  1  1/228 (0.44%)  0/231 (0.00%)  0/229 (0.00%) 
Restlessness  1  1/228 (0.44%)  0/231 (0.00%)  0/229 (0.00%) 
Suicidal Ideation  1  1/228 (0.44%)  0/231 (0.00%)  0/229 (0.00%) 
Mania  1  0/228 (0.00%)  1/231 (0.43%)  0/229 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Quetiapine XR Mono Add-on Quetiapine XR Add-on Lithium
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   93/228 (40.79%)   90/231 (38.96%)   41/229 (17.90%) 
Gastrointestinal disorders       
Dry mouth  2  13/228 (5.70%)  22/231 (9.52%)  6/229 (2.62%) 
General disorders       
Fatigue  2  21/228 (9.21%)  13/231 (5.63%)  7/229 (3.06%) 
Nervous system disorders       
Somnolence  1  22/228 (9.65%)  20/231 (8.66%)  0/229 (0.00%) 
Sedation  2  15/228 (6.58%)  11/231 (4.76%)  0/229 (0.00%) 
Tremor  2  0/228 (0.00%)  0/231 (0.00%)  15/229 (6.55%) 
Dizziness  2  11/228 (4.82%)  14/231 (6.06%)  0/229 (0.00%) 
Headache  2  11/228 (4.82%)  10/231 (4.33%)  13/229 (5.68%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10.0
2
Term from vocabulary, MedDRA (10.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Gerard Lynch
Organization: AstraZeneca
EMail: aztrial_results_posting@astrazeneca.com
Layout table for additonal information
Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT00789854     History of Changes
Other Study ID Numbers: D1443L00044
First Submitted: November 11, 2008
First Posted: November 13, 2008
Results First Submitted: August 4, 2010
Results First Posted: May 23, 2012
Last Update Posted: May 23, 2012