Comparative Effectiveness Study for Bipolar Disorder

Bipolar Disorder Clinical Trial

Official title:

Comparative Effectiveness of a Second Generation Antipsychotic Mood Stabilizer And a Classic Mood Stabilizer for Bipolar Disorder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01331304
• Other study ID #: 2010P001442
• Secondary ID: R01HS019371-01
• Status: Completed
• Phase: Phase 4
• First received: April 6, 2011
• Last updated: March 29, 2018
• Start date: September 2010
• Est. completion date: September 2013

Study information

• Verified date: March 2018
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the effectiveness of lithium and quetiapine for the treatment of individuals with bipolar disorder.

Description:

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 482
• Est. completion date: September 2013
• Est. primary completion date: April 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 68 Years

Eligibility

Inclusion Criteria:

1. Meets DSM-IV criteria for BD I or II, which is the primary focus of treatment

2. Able to give written informed consent

3. Age > to 18 years and < 68 years

4. Women of child bearing potential must agree to use adequate contraception (e.g. oral contraceptives, intrauterine device, barrier methods, or total abstinence from intercourse; Depo Provera is acceptable if it is started 3 months prior to enrollment), inform their doctor at the earliest possible time of their plans to conceive, and to understand the risks of lithium and other study treatments to the fetus and infant

5. Currently symptomatic, as defined as a Clinical Global Impression - Bipolar Disorder Overall Severity (CGI-BP-S) score of at least 3 (mild)

6. If currently taking an SGA, participants would be required to be willing to either discontinue or switch to QTP

7. Willing to be randomized to either QTP+APT or Li+APT.

Exclusion Criteria:

1. Unwilling or unable to comply with study requirements

2. If maintained on thyroid medication must be euthyroid for at least 1 month before Visit 1

3. Patients who have had intolerable side effects with QTP or Li

4. Patients whose clinical status requires inpatient care

5. Drug/alcohol dependence within the past 30 days

6. Pregnancy as determined by urine pregnancy test or breastfeeding

7. History of nonresponse to Li at a serum level of = 1.0 mEq/L = 8 weeks

8. History of nonresponse to QTP at doses of at least 600 mg = 8 weeks.

Related Conditions & MeSH terms

• Bipolar Disorder
• Disease

Intervention

Drug:
• Lithium
600-900mg per day over 6 months
• Quetiapine
100-800mg a day over 6 months

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Case Western Reserve University School of Medicine	Cleveland	Ohio
United States	The Lindner Center of HOPE	Mason	Ohio
United States	Vanderbilt University	Nashville	Tennessee
United States	Weill Cornell Medical College	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	The University of Texas Health Science Center	San Antonio	Texas
United States	Stanford University School of Medicine	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	Agency for Healthcare Research and Quality (AHRQ)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Clinical Global Impression-Efficacy Index (CGI-EI)	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.	Average 6 month score minus Average baseline score
Primary	Necessary Clinical Adjustments	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.	6 Months
Secondary	Risk of Cardiovascular Disease - Framingham Risk Score	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), with higher scores indicating higher risk. Established benchmarks exist for scores from 0 to 25--though it can exceed this value--that are meant to translate to the probability of developing heart disease.	Average baseline score minus Average 6 month score
Secondary	Longitudinal Interval Follow up Evaluation Range of Impaired Functioning Tool (LIFE-RIFT)	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. Summary scores can range from 4 to 20, with higher scores indicating greater functional impairment.	Average baseline score minus Average 6-month score