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

• 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: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Study Description

Brief Summary:

The primary objective of the study is to evaluate the efficacy of Quetiapine extended release (XR) in combination with an selective serotonin reuptake inhibitor (SSRI) or Venlafaxine versus Lithium in combination with an selective serotonin reuptake inhibitor or Venlafaxine versus Quetiapine extended release monotherapy in subjects with treatment resistant depression as assessed by the changes from randomisation to week 6 in the Montgomery-Åsberg Depression Rating Scale (MADRS) total score. As an independent objective, the primary objective will also be evaluated in two subgroups of patients: (1) patients who were resistant to two previous antidepressant therapies and (2) in the subgroup of patients with one previous failure.

Condition or disease	Intervention/treatment	Phase
Major Depressive Disorder; Treatment Resistant Depression	Drug: Quetiapine XR; Drug: Lithium carbonate; Drug: SSRI/Venlafaxine	Phase 3

Detailed Description:

The secondary objectives of the study are to compare the effects of the three different treatment regimen as assessed by the following variables and, if applicable, by their changes from randomisation to week 6 (end of study). Additionally the time of onset of therapeutic effect will be assessed by evaluating efficacy data after the first four days (Day 4) of treatment as well as after the first week of treatment (Day 8). These analyses will also be performed in the subgroups of patients with 2 failed previous antidepressants and patients with 1 failure.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 688 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomised, 6-week, Multicentre, Open-label, Rater-blinded Parallel Group Study Comparing Quetiapine Extended Release Monotherapy and Augmentation With Lithium Augmentation in Patients With Treatment Resistant Depression
• Study Start Date: November 2008
• Actual Primary Completion Date: August 2009
• Actual Study Completion Date: August 2009

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Add-on Quetiapine XR+SSRI/Venlafaxine; Selective serotonin reuptake inhibitors (SSRI) or Venlafaxine from previous therapy + add-on treatment with quetiapine XR, 300mg tablet once daily (od). From previous anti-depressant treatment 64% of the patients had SSRI and 35% had Venlafaxine at baseline.	Drug: Quetiapine XR; 300 mg once daily (od); Other Name: Seroquel XR; Drug: SSRI/Venlafaxine; SSRI - doses within label, Venlafaxine dose up to 225 mg/day
Active Comparator: Add-on Lithium+SSRI/Venlafaxine; Selective serotonin reuptake inhibitors (SSRI) or venlafaxine from previous therapy + add-on treatment with lithium, approximately 900mg tablet once daily (od). From previous anti-depressant treatment 67% of the patients had SSRI and 33% had Venlafaxine at baseline.	Drug: Lithium carbonate; 900 mg once daily (od); Other Name: Quilonum Retard; Drug: SSRI/Venlafaxine; SSRI - doses within label, Venlafaxine dose up to 225 mg/day
Active Comparator: Monotherapy Quetiapine XR; Switch from previous treatment with SSRI or venlafaxine to quetiapine XR monotherapy, 300mg tablet once daily (od)	Drug: Quetiapine XR; 300 mg once daily (od); Other Name: Seroquel XR

Outcome Measures

Primary Outcome Measures :

1. 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) [ Time Frame: 6 weeks treatment ]
   Change in LS mean total Montgomery Asberg Depression Rating Scale (MADRS) score from randomisation to end-of-treatment (week 6) (Scale 0-60), lower score indicates a better health status.
2. 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) [ Time Frame: 6 weeks of treatment ]
   Change in LS mean total Montgomery Asberg Depression Rating Scale (MADRS) score from randomisation to end-of-treatment (week 6) (Scale 0-60), lower score indicates a better health status.

Secondary Outcome Measures :

1. Depression Remission; Montgomery-Asberg Depression Rating Scale MADRS ≤10, All Patients [ Time Frame: 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.
2. Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤10, Patients With One Previous Treatment Failure [ Time Frame: 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.
3. Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤10, Patients With Two Previous Treatment Failure [ Time Frame: 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.
4. Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤8 [ Time Frame: 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.
5. Depression Remission; Montgomery-Asberg Depression Rating Scale (MADRS) ≤12 [ Time Frame: 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.
6. Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, All Patients [ Time Frame: 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
7. Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, Patients With One Previous Treatment Failure [ Time Frame: 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
8. Response Rate; Montgomery-Asberg Depression Rating Scale (MADRS) Score Reduced ≥ 50%, Patients With Two Previous Treatment Failure [ Time Frame: 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
9. Responder: Clinical Global Impression Improvement (CGI-I) Item 2, All Patients [ Time Frame: 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.
10. Responder: Clinical Global Impression Improvement (CGI)-I Item 2, Patients With One Previous Treatment Failure [ Time Frame: 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.
11. Responder: Clinical Global Impression Improvement (CGI-I) Item 2, Patients With Two Previous Treatment Failure [ Time Frame: 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.
12. Change in Clinical Global Impression Scale (CGI-S), All Patients [ Time Frame: 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.
13. Change in Clinical Global Impression Scale (CGI-S), Patients With One Previous Treatment Failure [ Time Frame: 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.
14. Change in Clinical Global Impression Scale (CGI-S), Patients With Two Previous Treatment Failure [ Time Frame: 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.
15. Change in Beck Depression Inventory (BDI) [ Time Frame: 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.
16. Change in Pain, Measured by Visual Analog Scale (VAS) [ Time Frame: 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.
17. Change in Anxiety Measured by Visual Analog Scale (VAS) [ Time Frame: 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.
18. Change in Anxiety Measured by State-Trait Anxiety Inventory (STAI), State Anxiety Inventory [ Time Frame: 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)
19. Change in Anxiety Measured by STAI, Trait Anxiety Inventory [ Time Frame: 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)
20. Change in Sleep Quality Measured by Montgomery Asberg Depression Rating Scale (MADRS), Item 4 [ Time Frame: 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)
21. Change in Sleep Quality Measured by Pittsburgh Sleep Quality Index (PSQI) [ Time Frame: 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)
22. Change in Quality of Life Measured by Short-form Health Survey (SF-36), Mental Component [ Time Frame: 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)
23. Change in Quality of Life Measured by Short-form Health Survey (SF-36), Physical Component [ Time Frame: 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)
24. Change in Quality of Life Measured by Health Questionnaire EQ-5D as Utility [ Time Frame: 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)
25. Change in Work Productivity and Activity Impairment: General Health (WPAI:GH) [ Time Frame: 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)
26. Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, All Patients [ Time Frame: 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).
27. Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, Patients With One Previous Treatment Failure [ Time Frame: 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.
28. Change in Clinical Global Impression (CGI) Item 4 Efficacy and Safety Combined, Patients With Two Previous Treatment Failures [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Documented clinical diagnosis as confirmed by the M.I.N.I. meeting criteria from the Diagnostic and Statistical Manual of Mental disorders, 4th Edition (DSM-IV) for any of the following:296.2x MDD, Single Episode296.3x MDD, Recurrent Episode
• Current episode of depression present, at least 42 days prior to enrolment but not more than 18 months
• MADRS-Score ≥ 25 at enrolment and randomisation

Exclusion Criteria:

• Patients with a DSM-IV Axis I disorder other than MDD within 6 months of randomisation
• Patients with a diagnosis of DSM-IV Axis II disorder which has a major impact on the patient's current psychiatric status
• Patients who, in the investigator's judgment pose a current serious suicidal or homicidal risk, or have made a suicide attempt within the past 6 months

Contacts and Locations

  Show 106 Study Locations

Sponsors and Collaborators

AstraZeneca

Investigators

• Principal Investigator: Michael Bauer, professor; Germany
• Study Director: Birgit Ekholm, PhD; AstraZeneca MC Sweden

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Bauer M, Dell'osso L, Kasper S, Pitchot W, Dencker Vansvik E, Köhler J, Jørgensen L, Montgomery SA. Extended-release quetiapine fumarate (quetiapine XR) monotherapy and quetiapine XR or lithium as add-on to antidepressants in patients with treatment-resistant major depressive disorder. J Affect Disord. 2013 Oct;151(1):209-19. doi: 10.1016/j.jad.2013.05.079. Epub 2013 Jun 27.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT00789854 History of Changes
• Other Study ID Numbers: D1443L00044
• First Posted: November 13, 2008
• Results First Posted: May 23, 2012
• Last Update Posted: May 23, 2012
• Last Verified: April 2012

Keywords provided by AstraZeneca:

Depression; MDD; TRD

Additional relevant MeSH terms:

Depression; Depressive Disorder; Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Behavioral Symptoms; Mood Disorders; Mental Disorders; Quetiapine Fumarate; Lithium Carbonate; Venlafaxine Hydrochloride; Antidepressive Agents; Psychotropic Drugs; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Physiological Effects of Drugs; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Antimanic Agents; Serotonin and Noradrenaline Reuptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Neurotransmitter Agents; Antidepressive Agents, Second-Generation