Comparative Effectiveness Study for Bipolar Disorder
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Comparative Effectiveness of a Second Generation Antipsychotic Mood Stabilizer And a Classic Mood Stabilizer for Bipolar Disorder|
- Clinical Global Impression-Efficacy Index (CGI-EI) [ Time Frame: Average 6 month score minus Average baseline score ] [ Designated as safety issue: Yes ]The CGI-EI integrates benefits and harms and yields a score that can be compared across interventions. It is made up of 2 subscales: therapeutic effects and side effects. Each rating is on a scale from 1 to 4. To combine these two subscales into the CGI-EI we report as our primary outcome, we subtracted the side effects subscale from the therapeutic effects subscale. Thus, the CGI-EI we report ranges the integers from -3 to +3 (i.e. possible scores are -3,-2,-1,0,1,2,3). A score of -3 is the most burdensome side effect score (4) and the least therapeutic effect score (1) and a score of +3 is the least burdensome side effect score (1) and the highest therapeutic effect score (4). Higher CGI-EI signifies better outcome (minimal side effects, maximal therapeutic effect). Lower CGI-EI signifies worse outcome (maximal side effects, minimal therapeutic effect).To compute CGI-EI score, we subtract the side effect score from the therapeutic effect score.
- Necessary Clinical Adjustments [ Time Frame: 6 Months ] [ Designated as safety issue: Yes ]Necessary Clinical Adjustment (NCA): The Medication Recommendation Tracking Form was developed and successfully implemented in a previous study to capture recommended medication changes at each study visit 17. Clinicians record dosage changes, missed doses, new medications added or discontinued, and specify the reason for each change. Any change in psychotropic medications, or medications used to treat side effects, is coded along with the reason for the change. NCAs include those changes made for lack of effectiveness or intolerance, but not changes for planned dose titrations.
- Risk of Cardiovascular Disease - Framingham Risk Score [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]The Framingham risk score captures the classic risk factors for cardiovascular disease, including age, sex, systolic blood pressure, total and high density lipoprotein cholesterol, diabetes mellitus, and smoking. The Framingham risk score is used as a simple predictive tool to determine 10-year (short term) risk for developing cardiovascular disease (CHD).
- Longitudinal Interval Follow up Evaluation Range of Impaired Functioning Tool (LIFE-RIFT) [ Time Frame: 6 months ] [ Designated as safety issue: No ]The LIFE-RIFT asses the extent to which psychopathology has impacted current functioning in work, household chores, interpersonal relationships with partner, family, and friends, recreational activities, and life, satisfaction, leisure activities and social relationships.
|Study Start Date:||September 2010|
|Study Completion Date:||September 2013|
|Primary Completion Date:||April 2013 (Final data collection date for primary outcome measure)|
Li + APT
Study participants will take lithium in addition to any other medications recommended by the study physician.
600-900mg per day over 6 months
Other Name: Lithoboid, Eskalith
QTP + APT
Study participants will take quetiapine in addition to any other medications recommended by the study physician.
100-800mg a day over 6 months
Other Name: Seroquel
Mood stabilizers, medications that prevent future mood episodes, are the foundation for treatment of bipolar disorder. While all published bipolar disorder treatment guidelines recommend that pharmacotherapy should include mood stabilizers for long-term maintenance treatment, no randomized comparative effectiveness studies have examined the real-world advantages and disadvantages of the newer second generation antipsychotic (SGA) mood stabilizers compared to the classic mood stabilizers, such as lithium (Li). No studies have looked at the effectiveness of SGAs compared to mood stabilizers when used in the context of other medications required to manage bipolar patients, since bipolar disorder patients take a median of 3 medications for optimal outcomes. Quetiapine (QTP) is the most extensively studied, broadly efficacious and the most widely prescribed SGA for bipolar disorder. The classic mood stabilizer Li has the largest evidence base for treating bipolar disorder, but has been largely supplanted by the SGAs.
Thus, this study compares symptomatic benefits and adverse effect burden between a QTP foundation with adjunctive personalized treatments (QTP+APT) and a mood stabilizer foundation consisting of Li with APT (Li+APT). APT will include any other medication needed with the following exceptions: the QTP+APT cannot receive Li and the Li+APT group cannot receive an antipsychotic. If, however, participants clinically require a switch to, or the addition of any other SGA or mood stabilizer, then those medications can be added as a rescue strategy that will be carefully recorded. Consistent with an effectiveness trial, participants will be able to continue in the study if they require a rescue treatment. The specific plan is a randomized, open, two arm, comparative effectiveness study of QTP+APT vs. Li+APT treatment for 6 months across 10 sites.
In summary, this comparative effectiveness study compares fundamentally different acute and continuation treatments for bipolar disorder. The investigators address the key question of whether to use a prototypical mood stabilizing SGA (i.e., QTP) or the classical mood stabilizer Li as the foundational treatment in the context of other necessary adjunctive personalized treatments (APT).
Please refer to this study by its ClinicalTrials.gov identifier: NCT01331304
|United States, Alabama|
|University of Alabama at Birmingham|
|Birmingham, Alabama, United States, 35205|
|United States, California|
|Stanford University School of Medicine|
|Stanford, California, United States, 94305|
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|United States, Michigan|
|University of Michigan|
|Ann Arbor, Michigan, United States, 48109|
|United States, New York|
|Weill Cornell Medical College|
|New York, New York, United States, 10065|
|United States, Ohio|
|Case Western Reserve University School of Medicine|
|Cleveland, Ohio, United States, 44106|
|The Lindner Center of HOPE|
|Mason, Ohio, United States, 45040|
|United States, Pennsylvania|
|University of Pennsylvania|
|Philadelphia, Pennsylvania, United States, 19104|
|University of Pittsburgh Medical Center|
|Pittsburgh, Pennsylvania, United States, 15213|
|United States, Tennessee|
|Nashville, Tennessee, United States, 37212|
|United States, Texas|
|The University of Texas Health Science Center|
|San Antonio, Texas, United States, 78229|
|Principal Investigator:||Andrew A Nierenberg, MD||Massachusetts General Hospital|