Bipolar CHOICE (Clinical Health Outcomes Initiative in Comparative Effectiveness): a pragmatic 6-month trial of lithium versus quetiapine for bipolar disorder.

Abstract

BACKGROUND:

Bipolar disorder is among the 10 most disabling medical conditions worldwide. While lithium has been used extensively for bipolar disorder since the 1970s, second-generation antipsychotics (SGAs) have supplanted lithium since 1998. To date, no randomized comparative-effectiveness study has compared lithium and any SGA.

METHOD:

Within the duration of the study (September 2010-September 2013), participants with bipolar I or II disorder (DSM-IV-TR) were randomized for 6 months to receive lithium (n = 240) or quetiapine (n = 242). Lithium and quetiapine were combined with other medications for bipolar disorder consistent with typical clinical practice (adjunctive personalized treatment [APT], excluding any SGA for the lithium + APT group and excluding lithium or any other SGA for the quetiapine + APT group). Coprimary outcome measures included Clinical Global Impressions-Efficacy Index (CGI-EI) and necessary clinical adjustments, which measured number of changes in adjunctive personalized treatment. Secondary measures included a full range of symptoms, cardiovascular risk, functioning, quality of life, suicidal ideation and behavior, and adverse events.

RESULTS:

Participants improved across all measures, and over 20% had a sustained response. Primary (CGI-EI, P = .59; necessary clinical adjustments, P = .15) and secondary outcome changes were not statistically significantly different between the 2 groups. For participants with greater manic/hypomanic symptoms, CGI-EI changes were significantly more favorable with quetiapine + APT (P = .02). Among those with anxiety, the lithium + APT group had fewer necessary clinical adjustments per month (P = .02). Lithium was better tolerated than quetiapine in terms of the burden of side effects frequency (P = .05), intensity (P = .01), and impairment (P = .01).

CONCLUSIONS:

Despite adequate power to detect clinically meaningful differences, we found outcomes with lithium + APT and quetiapine + APT were not significantly different across 6 months of treatment for bipolar disorder.

TRIAL REGISTRATION:

ClinicalTrials.gov identifier for the Bipolar CHOICE study: NCT01331304.

• Authors: Andrew A Nierenberg, Susan L McElroy, Edward S Friedman, Terence A Ketter, Richard C Shelton, Thilo Deckersbach, Melvin G McInnis, Charles L Bowden, Mauricio Tohen, James H Kocsis, Joseph R Calabrese, Gustavo Kinrys, William V Bobo, Vivek Singh, Masoud Kamali, David Kemp, Benjamin Brody, Noreen A Reilly-Harrington, Louisa G Sylvia, Leah W Shesler, Emily E Bernstein, David Schoenfeld, Dustin J Rabideau, Andrew C Leon, Stephen Faraone, Michael E Thase
• Journal: The Journal of clinical psychiatry (J Clin Psychiatry) Vol. 77 Issue 1 Pg. 90-9 (Jan 2016) ISSN: 1555-2101 [Electronic] United States
• PMID: 26845264 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Pragmatic Clinical Trial, Randomized Controlled Trial, Research Support, U.S. Gov't, P.H.S.)
• Copyright: © Copyright 2016 Physicians Postgraduate Press, Inc.

Chemical References

• Antipsychotic Agents
• Quetiapine Fumarate
• Lithium

Topics

• Adult
• Antipsychotic Agents (adverse effects, therapeutic use)
• Bipolar Disorder (drug therapy)
• Female
• Humans
• Lithium (adverse effects, therapeutic use)
• Male
• Middle Aged
• Quetiapine Fumarate (adverse effects, therapeutic use)
• Treatment Outcome