Comparative Effectiveness Study for Bipolar Disorder

Mass General Brigham

Status and phase: Completed; Phase 4

Conditions: Bipolar Disorder

Treatments: Drug: Lithium; Drug: Quetiapine

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT01331304

R01HS019371-01 (U.S. AHRQ Grant/Contract)

2010P001442

Details and patient eligibility

About

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

Full 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).

Enrollment: 482 patients

Sex: All

Ages: 18 to 68 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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482 participants in 2 patient groups

Li + APT

Other group

Description:

Study participants will take lithium in addition to any other medications recommended by the study physician.

Treatment:

Drug: Lithium

QTP + APT

Other group

Description:

Study participants will take quetiapine in addition to any other medications recommended by the study physician.

Treatment:

Drug: Quetiapine