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Complexity of Illness and Adjunctive Benzodiazepine Use in Outpatients With Bipolar I or II Disorder: Results From the Bipolar CHOICE Study

Bobo, William V. MD, MPH*; Reilly-Harrington, Noreen A. PhD; Ketter, Terence A. MD; Brody, Benjamin D. MD§; Kinrys, Gustavo MD; Kemp, David E. MD; Shelton, Richard C. MD; McElroy, Susan L. MD#; Sylvia, Louisa G. PhD; Kocsis, James H. MD§; McInnis, Melvin G. MD**; Friedman, Edward S. MD††; Singh, Vivek MD‡‡; Tohen, Mauricio MD, DrPH, MBA§§; Bowden, Charles L. MD‡‡; Deckersbach, Thilo PhD; Calabrese, Joseph R. MD; Thase, Michael E. MD∥∥; Nierenberg, Andrew A. MD; Rabideau, Dustin J. MS; Schoenfeld, David A. PhD; Faraone, Stephen V. PhD¶¶; Kamali, Masoud MD**

Journal of Clinical Psychopharmacology: February 2015 - Volume 35 - Issue 1 - p 68–74
doi: 10.1097/JCP.0000000000000257
Brief Reports

Benzodiazepines are widely prescribed for patients with bipolar disorders in clinical practice, but very little is known about the subtypes of patients with bipolar disorder or aspects of bipolar illness that contribute most to benzodiazepine use. We examined the prevalence of and factors associated with benzodiazepine use among 482 patients with bipolar I or II disorder enrolled in the Bipolar CHOICE study. Eighty-one subjects were prescribed benzodiazepines at study entry and were considered benzodiazepine users. Stepwise logistic regression was used to model baseline benzodiazepine use versus nonuse, using entry and exit criteria of P < 0.1. In bivariate analyses, benzodiazepine users were prescribed a significantly higher number of other psychotropic medications and were more likely to be prescribed lamotrigine or antidepressants as compared with benzodiazepine nonusers. Benzodiazepine users were more likely to have a diagnosis of bipolar I disorder and comorbid anxiety disorder, but not comorbid alcohol or substance use disorders. Benzodiazepine users also had experienced more anxiety and depressive symptoms and suicidality, but not irritability or manic symptoms, than did benzodiazepine nonusers. In the multivariate model, anxiety symptom level (regardless of diagnosis), lamotrigine use, number of concomitant psychotropic medications, college education, and high household income predicted benzodiazepine use. Benzodiazepine use in patients with bipolar disorders is associated with greater illness complexity as indicated by a higher number of concomitant psychotropic medications and higher anxiety symptom burden, regardless of a comorbid anxiety disorder diagnosis. Demographic factors were also important determinants of benzodiazepine use, which may be related to access to care and insurance coverage for benzodiazepines.

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From the *Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN; †Department of Psychiatry, The Massachusetts General Hospital, Boston, MA; ‡Department of Psychiatry and Behavioral Sciences and the Bipolar Disorders Clinic, Stanford University School of Medicine, Stanford, CA; §Department of Psychiatry, Weill Cornell Medical College of Cornell University, New York, NY; ∥Department of Psychiatry, University Hospitals Case Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH; ¶Department of Psychiatry, University of Alabama-Birmingham School of Medicine, Birmingham, AL; #Lindner Center of HOPE, Mason, Ohio and Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, OH; **Department of Psychiatry and Depression Center, The University of Michigan, Ann Arbor, MI; ††Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA; ‡‡Department of Psychiatry, University of Texas Health Science Center at San Antonio, San Antonio, TX; §§Department of Psychiatry, University of New Mexico, Health Sciences Center, Albuquerque, NM; ∥∥Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA; and ¶¶Department of Psychiatry, Upstate Medical University, State University of New York, Syracuse, NY.

Received January 16, 2014; accepted after revision October 6, 2014.

Reprints: William V. Bobo, MD, MPH, Department of Psychiatry and Psychology, Mayo Clinic, 200 First St SW, Generose 2A, Rochester, MN (e-mail:

This research was funded by the Agency for Healthcare Research and Quality (AHRQ): 1R01HS019371-01.

Clinical Trials Registration:; NCT01331304.

Supplemental digital contents are available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (

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