title: Effect of adjunctive benzodiazepines on clinical outcomes in lithium- or quetiapine-treated outpatients with bipolar I or II disorder: results from the Bipolar CHOICE trial.
abstract: BACKGROUND
  Little is known about the longer-term effects of adjunctive benzodiazepines on symptom response during treatment in patients with bipolar disorders.
  
  
  METHODS
  The study sample consisted of 482 patients with bipolar I or II disorder enrolled in a 6-month, randomized, multi-site comparison of lithium- and quetiapine-based treatment. Changes in clinical measures (BISS total and subscales, CGI-BP, and CGI-Efficacy Index) were compared between participants who did and did not receive benzodiazepine treatment at baseline or during follow-up. Selected outcomes were also compared between patients who did and did not initiate benzodiazepines during follow-up using stabilized inverse probability weighted analyses.
  
  
  RESULTS
  Significant improvement in all outcome measures occurred within each benzodiazepine exposure group. Benzodiazepine users (at baseline or during follow-up) experienced significantly less improvement in BISS total, BISS irritability, and CGI-BP scores than did benzodiazepine non-users. There were no significant differences in these measures between patients who did and did not initiate benzodiazepines during follow-up in the weighted analyses. There was no significant effect of benzodiazepine use on any outcome measure in patients with comorbid anxiety or substance use disorders.
  
  
  CONCLUSIONS
  This is a secondary analysis of data from a randomized effectiveness trial that was not designed to address differential treatment response according to benzodiazepine use.
  
  
  CONCLUSIONS
  Adjunctive benzodiazepines may not significantly affect clinical outcome in lithium- or quetiapine-treated patients with bipolar I or II disorder over 6 months, after controlling for potential confounding factors.
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA. Electronic address: bobo.william@mayo.edu.
authors.forename: William V
authors.initials: WV
authors.lastname: Bobo
authors.affiliation: The Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Noreen A
authors.initials: NA
authors.lastname: Reilly-Harrington
authors.affiliation: Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Terence A
authors.initials: TA
authors.lastname: Ketter
authors.affiliation: Weill Cornell Medical College of Cornell University, New York, NY, USA.
authors.forename: Benjamin D
authors.initials: BD
authors.lastname: Brody
authors.affiliation: The Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Kinrys
authors.affiliation: Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Kemp
authors.affiliation: University of Alabama-Birmingham School of Medicine, Birmingham, AL, USA.
authors.forename: Richard C
authors.initials: RC
authors.lastname: Shelton
authors.affiliation: Lindner Center for HOPE, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: McElroy
authors.affiliation: The Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Louisa G
authors.initials: LG
authors.lastname: Sylvia
authors.affiliation: Weill Cornell Medical College of Cornell University, New York, NY, USA.
authors.forename: James H
authors.initials: JH
authors.lastname: Kocsis
authors.affiliation: University of Michigan School of Medicine, Ann Arbor, MI, USA.
authors.forename: Melvin G
authors.initials: MG
authors.lastname: McInnis
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
authors.forename: Edward S
authors.initials: ES
authors.lastname: Friedman
authors.affiliation: University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Vivek
authors.initials: V
authors.lastname: Singh
authors.affiliation: University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Tohen
authors.affiliation: University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Charles L
authors.initials: CL
authors.lastname: Bowden
authors.affiliation: The Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Thilo
authors.initials: T
authors.lastname: Deckersbach
authors.affiliation: Case Western Reserve University School of Medicine, Cleveland, OH, USA.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Calabrese
authors.affiliation: Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Thase
authors.affiliation: The Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Nierenberg
authors.affiliation: The Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Dustin J
authors.initials: DJ
authors.lastname: Rabideau
authors.affiliation: The Massachusetts General Hospital, Boston, MA, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Schoenfeld
authors.affiliation: Upstate Medical University, State University of New York, Syracuse, NY, USA.
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
authors.affiliation: University of Michigan School of Medicine, Ann Arbor, MI, USA.
authors.forename: Masoud
authors.initials: M
authors.lastname: Kamali
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000523:psychology; D003987:Dibenzothiazepines / Q000627:therapeutic use; D005260:Female; D006801:Humans; D018020:Lithium Compounds / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000069348:Quetiapine Fumarate; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D018020:Lithium Compounds; D001569:Benzodiazepines; D000069348:Quetiapine Fumarate
keywords: Benzodiazepines; Bipolar disorder; Clinical outcome; Lithium; Quetiapine
references.citation: J Clin Psychiatry. 2005;66 Suppl 2:9-13
references.pmid: 15762814
references.citation: J Clin Psychiatry. 1998;59 Suppl 20:22-33;quiz 34-57
references.pmid: 9881538
references.citation: Psychiatry Res. 2010 Feb 28;175(3):221-6
references.pmid: 20022384
references.citation: CNS Drugs. 2004;18(1):37-48
references.pmid: 14731058
references.citation: Hum Psychopharmacol. 2006 Jul;21(5):319-25
references.pmid: 16856216
references.citation: Clin Trials. 2014 Feb;11(1):114-27
references.pmid: 24346608
references.citation: Acta Psychiatr Scand. 2007 Sep;116(3):189-94
references.pmid: 17655560
references.citation: Psychiatr Serv. 2007 Jan;58(1):85-91
references.pmid: 17215417
references.citation: Curr Psychiatry Rep. 2012 Dec;14(6):676-86
references.pmid: 22986995
references.citation: Psychiatry Res. 1997 Dec 5;73(3):159-71
references.pmid: 9481807
references.citation: Epidemiology. 2000 Sep;11(5):561-70
references.pmid: 10955409
references.citation: J Clin Psychiatry. 2004 Feb;65(2):151-5
references.pmid: 15003066
references.citation: J Clin Psychiatry. 2010 Feb;71(2):194-200
references.pmid: 20193647
references.citation: J Clin Psychiatry. 2004;65 Suppl 5:7-12
references.pmid: 15078112
references.citation: Psychiatr Serv. 2003 Oct;54(10):1395-401
references.pmid: 14557527
references.citation: Eur Neuropsychopharmacol. 2003 Mar;13(2):129-34
references.pmid: 12650958