Quetiapine XR Versus Sertraline in Acute Bipolar Depression as add-on Therapy

Study Overview
=================
Brief Summary
-----------------
Prospective, open-label, controlled (active comparator), randomized study of 8 weeks follow-up for the evaluation of the efficacy of extended release quetiapine (quetiapine XR) versus Sertraline in addition to previous mood stabilizer treatment (lithium or valproate at stable and clinically therapeutic blood levels) in the treatment of the adult bipolar depression. This multicentric study will be featured in two sites in Spain.

Official Title
-----------------
Effectiveness of Quetiapine XR Versus Sertraline in Acute Depression as add-on Therapy to Previous Mood Stabilizer Treatment: a Pilot Study

Conditions
-----------------
Bipolar Disorder, Bipolar Depression

Intervention / Treatment
-----------------
* Drug: Extended release quetiapine (quetiapine XR)
* Drug: Sertraline
* Drug: adequate mood stabilizer


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult ambulatory patients diagnosed of bipolar disorder I or II, current depressive episode (DSM-IV-TR 4ª Ed: 296.5x or 296.89 codes) Have been treated with only one mood stabilizer (lithium or valproate) in optimal and stable doses during at least the previous 4 weeks to randomization Hamilton Depression Rating Scale (HDRS-17) total score ≥ 20 and Young Mania Rating Scale (YMRS) total score ≤ 14 at the screening and randomization visits - Informed consent signed Exclusion Criteria: Patients with any axis I or II Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision (DSM-IV-TR) diagnoses different from bipolar disorder I or II - Length of current depressive episode less than 2 weeks or more than 12 months Having been treated with more than one mood stabilizer or any mood stabilizer other than Lithium or valproate, any antidepressant, any antipsychotic or any CP450-3A inductor/inhibitor within the 7 days period prior to randomization

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Quetiapine Extended Release<br>Lithium or valproate at stable doses within seric therapeutic levels | Drug: Extended release quetiapine (quetiapine XR)<br>* Flexible dose from 300 to 600 mg/d (combination of tablets of 50mg, 200mg and 300mg) oral, daily, 8 weeks length. Quetiapine XR was initiated at 50 mg/day and titrated to 100 mg on day 2, 200 mg on day 3, 300 mg on day 4, and flexible doses of 300 to 600 mg/d from day 5 to the end of the study.<br>* Other names: SEROQUEL XR®;Drug: adequate mood stabilizer<br>* An adequate mood stabilizer treatment with lithium or valproate(defined as a serum concentration of 0.5-1.2 mEq/L or 50-100 microg/ml, respectively).<br>|
| Active Comparator: Sertraline<br>Lithium or valproate at stable doses within seric therapeutic levels | Drug: Sertraline<br>* Flexible dose from 50 to 200 mg/d (combination of tablets of 50mg and 100mg) oral, daily, 8 weeks length. Sertraline titration: 50 mg on day 1-3, 100 mg on day 4, and flexible doses of 50 to 200 mg/d from day 5 to the end of the study.<br>* Other names: Zoloft;Drug: adequate mood stabilizer<br>* An adequate mood stabilizer treatment with lithium or valproate(defined as a serum concentration of 0.5-1.2 mEq/L or 50-100 microg/ml, respectively).<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Mean Change From Baseline to Week 2 in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score | MADRS assesses severity of depressive symptoms. It ranges from a minimum of 0 to a maximum of 60 (higher scores indicating a greater severity of depressive symptoms) | baseline, week 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Mean Change From Baseline to Week 1 in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score | MADRS assesses severity of depressive symptoms. It ranges from a minimum of 0 to a maximum of 60 (higher scores indicating a greater severity of depressive symptoms) | baseline, week 1 | 
| The Mean Change From Baseline to Week 4 in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score | MADRS assesses severity of depressive symptoms. It ranges from a minimum of 0 to a maximum of 60 (higher scores indicating a greater severity of depressive symptoms) | baseline, week 4 | 
| The Mean Change From Baseline to Week 8 in the Montgomery Asberg Depression Rating Scale (MADRS) Total Score | MADRS assesses severity of depressive symptoms. It ranges from a minimum of 0 to a maximum of 60 (higher scores indicating a greater severity of depressive symptoms) | baseline. week 8 | 
| The Mean Change From Baseline to Week 1 in the Clinical Impression Global Scale - Bipolar (CGI-BP-M) Total Score | CGI-BP-M assesses severity of clinical status. It ranges from a minimum of 1 to a maximum of 7 ( higher scores indicating a greater clinical severity) | baseline, week 1 | 
| The Mean Change From Baseline to Week 2 in the Clinical Impression Global Scale - Bipolar (CGI-BP-M) Total Score | CGI-BP-M assesses severity of clinical status. It ranges from a minimum of 1 to a maximum of 7 ( higher scores indicating a greater clinical severity) | baseline, week 2 | 
| The Mean Change From Baseline to Week 4 in the Clinical Impression Global Scale - Bipolar (CGI-BP-M) Total Score | CGI-BP-M assesses severity of clinical status. It ranges from a minimum of 1 to a maximum of 7 ( higher scores indicating a greater clinical severity) | baseline, week 4 | 
| The Mean Change From Baseline to Week 8 in the Clinical Impression Global Scale - Bipolar (CGI-BP-M) Total Score | CGI-BP-M assesses severity of clinical status. It ranges from a minimum of 1 to a maximum of 7 (higher scores indicating a greater clinical severity) | baseline, week 8 | 
| The Mean Change From Baseline to Week 4 in the Hamilton Anxiety Rating Scale (HARS) Total Score | HARS assesses severity of anxiety symptoms. It ranges from a minimum of 0 to a maximum of 56 (higher scores indicating a greater severity of anxiety symptoms) | baseline, week 4 | 
| The Mean Change From Baseline to Week 8 in the Hamilton Anxiety Rating Scale (HARS) Total Score | HARS assesses severity of anxiety symptoms. It ranges from a minimum of 0 to a maximum of 56 (higher scores indicating a greater severity of anxiety symptoms) | baseline, week 8 | 
| Number of Patients Response at Week 1 | Number of patients responded to the treatment at week 1, where response is defined as ≥ 50% reduction in the Montgomery Asberg Depression Rating Scale (MADRS) total score from baseline to week 1. MADRS assesses severity of depressive symptoms. It ranges from a minimum of 0 to a maximum of 60 (higher scores indicating a greater severity of depressive symptoms. | week 1 | 
| Number of Patients With Response at Week 2 | Number of patients responded to the treatment at week 2, where response is defined as ≥ 50% reduction in the Montgomery Asberg Depression Rating Scale (MADRS) total score from baseline to week 2. MADRS assesses severity of depressive symptoms. It ranges from a minimum of 0 to a maximum of 60 (higher scores indicating a greater severity of depressive symptoms. | week 2 | 
| Number of Patients With Response at Week 4. | Number of patients responded to the treatment at week 4, where response is defined as ≥ 50% reduction in the Montgomery Asberg Depression Rating Scale (MADRS) total score from baseline to week 4. MADRS assesses severity of depressive symptoms. It ranges from a minimum of 0 to a maximum of 60 (higher scores indicating a greater severity of depressive symptoms. | week 4 | 
| Number of Patients With Response at Week 8. | Number of patients responded to the treatment at week 8, where response is defined as ≥ 50% reduction in the Montgomery Asberg Depression Rating Scale (MADRS) total score from baseline to week 8. MADRS assesses severity of depressive symptoms. It ranges from a minimum of 0 to a maximum of 60 (higher scores indicating a greater severity of depressive symptoms. | week 8 | 
| Number of Patients With Remission at Week 1. | Number of patients who achieved remission at week 1, where remission is defined as Montgomery Asberg Depression Rating Scale (MADRS) total score ≤ 10. MADRS assesses severity of depressive symptoms. It ranges from a minimum of 0 to a maximum of 60 (higher scores indicating a greater severity of depressive symptoms. | week 1 | 
| Number of Patients With Remission at Week 2. | Number of patients who achieved remission at week 2, where remission is defined as Montgomery Asberg Depression Rating Scale (MADRS) total score ≤ 10. MADRS assesses severity of depressive symptoms. It ranges from a minimum of 0 to a maximum of 60 (higher scores indicating a greater severity of depressive symptoms. | week 2 | 
| Number of Patients With Remission at Week 4. | Number of patients who achieved remission at week 4, where remission is defined as Montgomery Asberg Depression Rating Scale (MADRS) total score ≤ 10. MADRS assesses severity of depressive symptoms. It ranges from a minimum of 0 to a maximum of 60 (higher scores indicating a greater severity of depressive symptoms. | week 4 | 
| Number of Patients With Remission at Week 8. | Number of patients who achieved remission at week 8, where remission is defined as Montgomery Asberg Depression Rating Scale (MADRS) total score ≤ 10. MADRS assesses severity of depressive symptoms. It ranges from a minimum of 0 to a maximum of 60 (higher scores indicating a greater severity of depressive symptoms. | week 8 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Bipolar disorder, Bipolar depression, quetiapine, sertraline