Clinical trial NCT01331304: Comparative Effectiveness Study for Bipolar Disorder
Official title: Comparative Effectiveness of a Second Generation Antipsychotic Mood Stabilizer And a Classic Mood Stabilizer for Bipolar Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Bipolar Disorder
Keywords: Bipolar disorder
Comparative effectiveness trial
Lithium
Quetiapine
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Agency for Healthcare Research and Quality (AHRQ)
First posted: 2011-04-08
Enrollment: 482
Sex: ALL
Minimum age (years): 18
Maximum age (years): 68
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Clinical Global Impression-Efficacy Index (CGI-EI)
timeFrame: Average 6 month score minus Average baseline score
measure: Necessary Clinical Adjustments
timeFrame: 6 Months
Secondary outcomes:
measure: Risk of Cardiovascular Disease - Framingham Risk Score
timeFrame: Average baseline score minus Average 6 month score
measure: Longitudinal Interval Follow up Evaluation Range of Impaired Functioning Tool (LIFE-RIFT)
timeFrame: Average baseline score minus Average 6-month score
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Cleveland
country: United States
facility: Case Western Reserve University School of Medicine
state: Ohio
city: Mason
country: United States
facility: The Lindner Center of HOPE
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: San Antonio
country: United States
facility: The University of Texas Health Science Center
state: Texas
Study officials:
affiliation: Massachusetts General Hospital
name: Andrew A Nierenberg, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.