Trial Outcomes & Findings for Comparing Quetiapine XR Monotherapy and Augmentation With Lithium Augmentation in TRD Patients (NCT NCT00789854)

NCT ID: NCT00789854

Last Updated: 2012-05-23

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 688 participants
• Primary outcome timeframe: 6 weeks treatment
• Results posted on: 2012-05-23

Participant Flow

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

At visit 1 and 2 (randomisation) the patients should have a Montgomery-Asberg Depression Rating Scale (MADRS) total score above or equal to 25

Participant milestones

Measure	Quetiapine XR Mono Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	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)	Add-on Lithium Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Study STARTED	228	231	229
Overall Study COMPLETED	179	196	182
Overall Study NOT COMPLETED	49	35	47

Reasons for withdrawal

Measure	Quetiapine XR Mono Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	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)	Add-on Lithium Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Overall Study Adverse Event	28	23	18
Overall Study Lost to Follow-up	1	1	4
Overall Study Withdrawal by Subject	9	6	17
Overall Study Eligibility criteria not fulfilled	2	5	1
Overall Study Severe non-compliance to the protocol	3	0	0
Overall Study Safety reasons	0	0	2
Overall Study Other	6	0	5

Baseline Characteristics

Comparing Quetiapine XR Monotherapy and Augmentation With Lithium Augmentation in TRD Patients

Baseline characteristics by cohort

Measure	Quetiapine XR Mono n=225 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=229 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=221 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)	Total n=675 Participants Total of all reporting groups
Age Continuous	47 years n=5 Participants	47 years n=7 Participants	47 years n=5 Participants	47 years n=4 Participants
Sex: Female, Male Female	152 Participants n=5 Participants	162 Participants n=7 Participants	152 Participants n=5 Participants	466 Participants n=4 Participants
Sex: Female, Male Male	73 Participants n=5 Participants	67 Participants n=7 Participants	69 Participants n=5 Participants	209 Participants n=4 Participants
Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Diagnose code 296.2x Major Depressive Disorder (MD	50 Participants n=5 Participants	36 Participants n=7 Participants	41 Participants n=5 Participants	127 Participants n=4 Participants
Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Diagnose code 296.3x MDD, Recurrent	175 Participants n=5 Participants	193 Participants n=7 Participants	180 Participants n=5 Participants	548 Participants n=4 Participants
Montgomery-Asberg Depression Rating Scale (MADRS) total score	33.74 Units on a scale STANDARD_DEVIATION 5.6 • n=5 Participants	33.15 Units on a scale STANDARD_DEVIATION 5.34 • n=7 Participants	32.91 Units on a scale STANDARD_DEVIATION 5.2 • n=5 Participants	33.32 Units on a scale STANDARD_DEVIATION 5.4 • n=4 Participants
Weight	75.3 kg STANDARD_DEVIATION 17.2 • n=5 Participants	75.2 kg STANDARD_DEVIATION 17 • n=7 Participants	76.4 kg STANDARD_DEVIATION 16.1 • n=5 Participants	75.8 kg STANDARD_DEVIATION 16.65 • n=4 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Quetiapine XR Mono n=180 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=183 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=109 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
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 • Interval 0.843 to	-17.2 scores on a scale Standard Error 0.826 • Interval 0.826 to	-14.9 scores on a scale Standard Error 0.97 • Interval 0.97 to

PRIMARY outcome

Timeframe: 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.

Outcome measures

Measure	Quetiapine XR Mono n=225 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=229 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=221 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
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 • Interval 0.806 to	-15.1 scores on a scale Standard Error 0.797 • Interval 0.797 to	-13.3 scores on a scale Standard Error 0.801 • Interval 0.801 to

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Quetiapine XR Mono n=225 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=229 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=221 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Depression Remission; Montgomery-Asberg Depression Rating Scale MADRS ≤10, All Patients	53 Participants	73 Participants	60 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Quetiapine XR Mono n=114 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=117 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=114 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤10, Patients With One Previous Treatment Failure	22 Participants	42 Participants	31 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Quetiapine XR Mono n=114 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=114 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=115 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤10, Patients With Two Previous Treatment Failure	31 Participants	31 Participants	29 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Quetiapine XR Mono n=225 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=229 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=221 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤8	35 Participants	58 Participants	45 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Quetiapine XR Mono n=225 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=229 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=221 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤12	67 Participants	89 Participants	73 Participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Quetiapine XR Mono n=225 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=229 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=221 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, All Patients	114 Participants	120 Participants	102 Participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Quetiapine XR Mono n=114 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=117 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=114 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, Patients With One Previous Treatment Failure	54 Participants	65 Participants	53 Participants

SECONDARY outcome

Timeframe: 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

Outcome measures

Measure	Quetiapine XR Mono n=114 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=114 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=115 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, Patients With Two Previous Treatment Failure	60 Participants	55 Participants	49 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Quetiapine XR Mono n=224 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=229 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=220 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Responder: Clinical Global Impression Improvement (CGI-I) Item 2, All Patients	-1.54 scores on a scale Standard Deviation 1.24	-1.85 scores on a scale Standard Deviation 1.34	-1.58 scores on a scale Standard Deviation 1.32

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Quetiapine XR Mono n=113 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=115 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=111 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
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	-1.91 scores on a scale Standard Deviation 1.31	-1.62 scores on a scale Standard Deviation 1.27

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Quetiapine XR Mono n=111 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=114 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=109 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Responder: Clinical Global Impression Improvement (CGI-I) Item 2, Patients With Two Previous Treatment Failure	-1.67 scores on a scale Standard Deviation 1.30	-1.79 scores on a scale Standard Deviation 1.36	-1.54 scores on a scale Standard Deviation 1.38

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Quetiapine XR Mono n=224 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=229 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=220 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Change in Clinical Global Impression Scale (CGI-S), All Patients	-1.43 scores on a scale Standard Error 0.101 • Interval 0.101 to	-1.65 scores on a scale Standard Error 0.099 • Interval 0.099 to	-1.49 scores on a scale Standard Error 0.1 • Interval 0.1 to

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Quetiapine XR Mono n=113 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=115 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=111 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Change in Clinical Global Impression Scale (CGI-S), Patients With One Previous Treatment Failure	-1.45 scores on a scale Standard Error 0.133 • Interval 0.133 to	-1.82 scores on a scale Standard Error 0.13 • Interval 0.13 to	-1.59 scores on a scale Standard Error 0.13 • Interval 0.13 to

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Quetiapine XR Mono n=111 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=114 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=109 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Change in Clinical Global Impression Scale (CGI-S), Patients With Two Previous Treatment Failure	-1.52 scores on a scale Standard Error 0.133 • Interval 0.133 to	-1.55 scores on a scale Standard Error 0.131 • Interval 0.131 to	-1.45 scores on a scale Standard Error 0.135 • Interval 0.135 to

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Quetiapine XR Mono n=213 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=212 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=205 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Change in Beck Depression Inventory (BDI)	-11.7 scores on a scale Standard Error 0.926 • Interval 0.926 to	-13.5 scores on a scale Standard Error 0.921 • Interval 0.921 to	-12.2 scores on a scale Standard Error 0.922 • Interval 0.922 to

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Quetiapine XR Mono n=221 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=222 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=218 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Change in Pain, Measured by Visual Analog Scale (VAS)	-9.47 scores on a scale Standard Error 1.695 • Interval 1.695 to	-8.03 scores on a scale Standard Error 1.681 • Interval 1.681 to	-8.3 scores on a scale Standard Error 1.682 • Interval 1.682 to

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Quetiapine XR Mono n=219 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=224 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=218 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Change in Anxiety Measured by Visual Analog Scale (VAS)	-21.2 scores on a scale Standard Error 1.972 • Interval 1.972 to	-23.4 scores on a scale Standard Error 1.947 • Interval 1.947 to	-20.6 scores on a scale Standard Error 1.952 • Interval 1.952 to

SECONDARY outcome

Timeframe: 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)

Outcome measures

Measure	Quetiapine XR Mono n=223 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=227 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=217 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Change in Anxiety Measured by State-Trait Anxiety Inventory (STAI), State Anxiety Inventory	-0.62 Scores on a scale Standard Error 0.347 • Interval 0.347 to	0.014 Scores on a scale Standard Error 0.344 • Interval 0.344 to	-0.87 Scores on a scale Standard Error 0.35 • Interval 0.35 to

SECONDARY outcome

Timeframe: 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)

Outcome measures

Measure	Quetiapine XR Mono n=220 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=220 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=214 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Change in Anxiety Measured by STAI, Trait Anxiety Inventory	-1.01 Scores on a scale Standard Error 0.331 • Interval 0.331 to	-1.36 Scores on a scale Standard Error 0.328 • Interval 0.328 to	-1.39 Scores on a scale Standard Error 0.331 • Interval 0.331 to

SECONDARY outcome

Timeframe: 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)

Outcome measures

Measure	Quetiapine XR Mono n=225 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=229 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=221 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Change in Sleep Quality Measured by Montgomery Asberg Depression Rating Scale (MADRS), Item 4	-2.2 MADRS item 4 score Standard Error 0.108 • Interval 0.108 to	-2.4 MADRS item 4 score Standard Error 0.107 • Interval 0.107 to	-1.63 MADRS item 4 score Standard Error 0.108 • Interval 0.108 to

SECONDARY outcome

Timeframe: 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)

Outcome measures

Measure	Quetiapine XR Mono n=200 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=196 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=185 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Change in Sleep Quality Measured by Pittsburgh Sleep Quality Index (PSQI)	-4.77 Scores on a scale Standard Error 0.36 • Interval 0.36 to	-4.96 Scores on a scale Standard Error 0.358 • Interval 0.358 to	-3.51 Scores on a scale Standard Error 0.364 • Interval 0.364 to

SECONDARY outcome

Timeframe: 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)

Outcome measures

Measure	Quetiapine XR Mono n=178 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=171 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=174 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
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 • Interval 0.929 to	10.77 Scores on a scale Standard Error 0.925 • Interval 0.925 to	9.66 Scores on a scale Standard Error 0.932 • Interval 0.932 to

SECONDARY outcome

Timeframe: 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)

Outcome measures

Measure	Quetiapine XR Mono n=178 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=171 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=174 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
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 • Interval 0.811 to	5.065 Scores on a scale Standard Error 0.813 • Interval 0.813 to	4.566 Scores on a scale Standard Error 0.817 • Interval 0.817 to

SECONDARY outcome

Timeframe: 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)

Outcome measures

Measure	Quetiapine XR Mono n=220 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=220 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=215 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Change in Quality of Life Measured by Health Questionnaire EQ-5D as Utility	0.184 Scores on a scale Standard Error 0.023 • Interval 0.023 to	0.224 Scores on a scale Standard Error 0.023 • Interval 0.023 to	0.208 Scores on a scale Standard Error 0.023 • Interval 0.023 to

SECONDARY outcome

Timeframe: 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)

Outcome measures

Measure	Quetiapine XR Mono n=31 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=39 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=25 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Change in Work Productivity and Activity Impairment: General Health (WPAI:GH)	-233 Scores on a scale Standard Error 0.023 • Interval 79.09 to	-185 Scores on a scale Standard Error 0.023 • Interval 72.38 to	-299 Scores on a scale Standard Error 0.023 • Interval 87.42 to

SECONDARY outcome

Timeframe: 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).

Outcome measures

Measure	Quetiapine XR Mono n=225 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=229 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=221 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, All Patients	135 Participants	146 Participants	131 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Quetiapine XR Mono n=113 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=115 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=111 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, Patients With One Previous Treatment Failure	67 Participants	75 Participants	69 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Measure	Quetiapine XR Mono n=112 Participants Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=114 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=110 Participants Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, Patients With Two Previous Treatment Failures	68 Participants	71 Participants	62 Participants

Adverse Events

Quetiapine XR Mono

Serious events: 5 serious events

Other events: 93 other events

Deaths: 0 deaths

Add-on Quetiapine XR

Serious events: 5 serious events

Other events: 90 other events

Deaths: 0 deaths

Add-on Lithium

Serious events: 2 serious events

Other events: 41 other events

Deaths: 0 deaths

Serious adverse events

Measure	Quetiapine XR Mono n=228 participants at risk Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=231 participants at risk Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=229 participants at risk Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Psychiatric disorders Depression	0.00% 0/228	1.3% 3/231	0.44% 1/229
Psychiatric disorders Affective Disorder	0.44% 1/228	0.00% 0/231	0.00% 0/229
Psychiatric disorders Psychotic Disorder	0.44% 1/228	0.00% 0/231	0.00% 0/229
Psychiatric disorders Restlessness	0.44% 1/228	0.00% 0/231	0.00% 0/229
Psychiatric disorders Suicidal Ideation	0.44% 1/228	0.00% 0/231	0.00% 0/229
Gastrointestinal disorders Diarrhoea	0.00% 0/228	0.43% 1/231	0.00% 0/229
Hepatobiliary disorders Cholelithiasis	0.00% 0/228	0.00% 0/231	0.44% 1/229
Psychiatric disorders Mania	0.00% 0/228	0.43% 1/231	0.00% 0/229
Injury, poisoning and procedural complications Overdose	0.44% 1/228	0.00% 0/231	0.00% 0/229

Other adverse events

Measure	Quetiapine XR Mono n=228 participants at risk Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Add-on Quetiapine XR n=231 participants at risk Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od)	Add-on Lithium n=229 participants at risk Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od)
Nervous system disorders Somnolence	9.6% 22/228	8.7% 20/231	0.00% 0/229
Nervous system disorders Sedation	6.6% 15/228	4.8% 11/231	0.00% 0/229
Nervous system disorders Tremor	0.00% 0/228	0.00% 0/231	6.6% 15/229
Nervous system disorders Dizziness	4.8% 11/228	6.1% 14/231	0.00% 0/229
Nervous system disorders Headache	4.8% 11/228	4.3% 10/231	5.7% 13/229
General disorders Fatigue	9.2% 21/228	5.6% 13/231	3.1% 7/229
Gastrointestinal disorders Dry mouth	5.7% 13/228	9.5% 22/231	2.6% 6/229

Additional Information

Gerard Lynch

AstraZeneca

Email: aztrial_results_posting@astrazeneca.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60