Comparative Effectiveness Study for Bipolar Disorder

NCT ID: NCT01331304

Last Updated: 2018-04-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 482 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-09-30
• Study Completion Date: 2013-09-30

Brief Summary

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

Detailed 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).

Conditions

Bipolar Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Li + APT

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

Group Type: OTHER

Lithium

Intervention Type: DRUG

600-900mg per day over 6 months

QTP + APT

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

Group Type: OTHER

Quetiapine

Intervention Type: DRUG

100-800mg a day over 6 months

Interventions

Lithium

600-900mg per day over 6 months

Intervention Type: DRUG

Quetiapine

100-800mg a day over 6 months

Intervention Type: DRUG

Other Intervention Names

Lithoboid, Eskalith; Seroquel

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 68 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Agency for Healthcare Research and Quality (AHRQ)

FED

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Andrew A. Nierenberg, MD

Director of Research, Bipolar Clinic and Research Program

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Andrew A Nierenberg, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Stanford University School of Medicine

Stanford, California, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

University of Michigan

Ann Arbor, Michigan, United States

Weill Cornell Medical College

New York, New York, United States

Case Western Reserve University School of Medicine

Cleveland, Ohio, United States

The Lindner Center of HOPE

Mason, Ohio, United States

University of Pennsylvania

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Vanderbilt University

Nashville, Tennessee, United States

The University of Texas Health Science Center

San Antonio, Texas, United States

Countries

United States

References

Sylvia LG, Montana RE, Deckersbach T, Thase ME, Tohen M, Reilly-Harrington N, McInnis MG, Kocsis JH, Bowden C, Calabrese J, Gao K, Ketter T, Shelton RC, McElroy SL, Friedman ES, Rabideau DJ, Nierenberg AA. Poor quality of life and functioning in bipolar disorder. Int J Bipolar Disord. 2017 Dec;5(1):10. doi: 10.1186/s40345-017-0078-4. Epub 2017 Mar 27.

Reference Type: DERIVED

PMID: 28188565 (View on PubMed)

Deckersbach T, Nierenberg AA, McInnis MG, Salcedo S, Bernstein EE, Kemp DE, Shelton RC, McElroy SL, Sylvia LG, Kocsis JH, Bobo WV, Friedman ES, Singh V, Tohen M, Bowden CL, Ketter TA, Calabrese JR, Thase ME, Reilly-Harrington NA, Rabideau DJ, Kinrys G, Kamali M. Baseline disability and poor functioning in bipolar disorder predict worse outcomes: results from the Bipolar CHOICE study. J Clin Psychiatry. 2016 Jan;77(1):100-8. doi: 10.4088/JCP.14m09210.

Reference Type: DERIVED

PMID: 26845265 (View on PubMed)

Nierenberg AA, McElroy SL, Friedman ES, Ketter TA, Shelton RC, Deckersbach T, McInnis MG, Bowden CL, Tohen M, Kocsis JH, Calabrese JR, Kinrys G, Bobo WV, Singh V, Kamali M, Kemp D, Brody B, Reilly-Harrington NA, Sylvia LG, Shesler LW, Bernstein EE, Schoenfeld D, Rabideau DJ, Leon AC, Faraone S, Thase ME. Bipolar CHOICE (Clinical Health Outcomes Initiative in Comparative Effectiveness): a pragmatic 6-month trial of lithium versus quetiapine for bipolar disorder. J Clin Psychiatry. 2016 Jan;77(1):90-9. doi: 10.4088/JCP.14m09349.

Reference Type: DERIVED

PMID: 26845264 (View on PubMed)

Bobo WV, Reilly-Harrington NA, Ketter TA, Brody BD, Kinrys G, Kemp DE, Shelton RC, McElroy SL, Sylvia LG, Kocsis JH, McInnis MG, Friedman ES, Singh V, Tohen M, Bowden CL, Deckersbach T, Calabrese JR, Thase ME, Nierenberg AA, Rabideau DJ, Schoenfeld DA, Faraone SV, Kamali M. Complexity of illness and adjunctive benzodiazepine use in outpatients with bipolar I or II disorder: results from the Bipolar CHOICE study. J Clin Psychopharmacol. 2015 Feb;35(1):68-74. doi: 10.1097/JCP.0000000000000257.

Reference Type: DERIVED

PMID: 25514063 (View on PubMed)

Other Identifiers

R01HS019371-01

Identifier Type: AHRQ

Identifier Source: secondary_id

View Link

2010P001442

Identifier Type: -

Identifier Source: org_study_id