title: 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.
  
  
  METHODS
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier for the Bipolar CHOICE study: NCT01331304.
authors: Massachusetts General Hospital, 50 Staniford St, Ste 580, Boston, MA 02114 anierenberg@mgh.harvard.edu.
authors: Andrew A
authors: AA
authors: Nierenberg
authors: Susan L
authors: SL
authors: McElroy
authors: Edward S
authors: ES
authors: Friedman
authors: Terence A
authors: TA
authors: Ketter
authors: Richard C
authors: RC
authors: Shelton
authors: Thilo
authors: T
authors: Deckersbach
authors: Melvin G
authors: MG
authors: McInnis
authors: Charles L
authors: CL
authors: Bowden
authors: Mauricio
authors: M
authors: Tohen
authors: James H
authors: JH
authors: Kocsis
authors: Joseph R
authors: JR
authors: Calabrese
authors: Gustavo
authors: G
authors: Kinrys
authors: William V
authors: WV
authors: Bobo
authors: Vivek
authors: V
authors: Singh
authors: Masoud
authors: M
authors: Kamali
authors: David
authors: D
authors: Kemp
authors: Benjamin
authors: B
authors: Brody
authors: Noreen A
authors: NA
authors: Reilly-Harrington
authors: Louisa G
authors: LG
authors: Sylvia
authors: Leah W
authors: LW
authors: Shesler
authors: Emily E
authors: EE
authors: Bernstein
authors: David
authors: D
authors: Schoenfeld
authors: Dustin J
authors: DJ
authors: Rabideau
authors: Andrew C
authors: AC
authors: Leon
authors: Stephen
authors: S
authors: Faraone
authors: Michael E
authors: ME
authors: Thase
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008094:Lithium / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000069348:Quetiapine Fumarate / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D000069348:Quetiapine Fumarate; D008094:Lithium