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Randomized Controlled Trial
. 2015 Feb;35(1):68-74.
doi: 10.1097/JCP.0000000000000257.

Complexity of illness and adjunctive benzodiazepine use in outpatients with bipolar I or II disorder: results from the Bipolar CHOICE study

Affiliations
Randomized Controlled Trial

Complexity of illness and adjunctive benzodiazepine use in outpatients with bipolar I or II disorder: results from the Bipolar CHOICE study

William V Bobo et al. J Clin Psychopharmacol. 2015 Feb.

Abstract

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.

Trial registration: ClinicalTrials.gov NCT01331304.

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Conflict of interest statement

Conflict of interest

Dr. Bobo reports no competing interests in the past three years.

Dr. Reilly-Harrington receives royalties from Oxford University Press, the American Psychological Association, and New Harbinger. She serves as a consultant for United Biosource Corporation and was a shareholder in Concordant Rater Systems.

Dr. Ketter, between May 14, 2010 and May 14, 2013, had the following financial interests/arrangements or affiliations that could be perceived as real or apparent conflicts of interest: Grant/Research Support from the AstraZeneca Pharmaceuticals LP, Cephalon Inc., Eli Lilly and Company, Pfizer Inc., and Sunovion Pharmaceuticals; Consultant Fees from Allergan, Inc., Avanir Pharmaceuticals, Bristol-Myers Squibb Company, Cephalon Inc., Forest Pharmaceuticals, Janssen Pharmaceutica Products, LP, Merck & Co., Inc., Sunovion Pharmaceuticals, Teva Pharmaceuticals; Lecture Honoraria from Abbott Laboratories, Inc., AstraZeneca Pharmaceuticals LP, GlaxoSmithKline, and Otsuka Pharmaceuticals; and Publication Royalties from American Psychiatric Publishing, Inc. In addition, Dr. Ketter′s spouse is an employee of and holds stock in Janssen Pharmaceuticals.

Dr. Brody has received salary support over the past 3 years from grants funded by Forrest, Agency for Healthcare Quality and Research, and Pritzker neuropsychiatric disorders research consortium.

Dr. Kinrys has received research support from Astra-Zeneca, Bristol-Myers Squibb Company, Cephalon, Elan Pharmaceuticals, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithkline, Sanofi/Synthelabo, Sepracor Inc., Pfizer Inc, UCB Pharma, and Wyeth-Ayerst Laboratories. He has been an advisor or consultant for Astra-Zeneca, Cephalon, Eli Lilly & Company, Forest Pharmaceuticals Inc., GlaxoSmithkline, Janssen Pharmaceutica, Pfizer Inc, Sepracor Inc., UCB Pharma, and Wyeth-Ayerst Laboratories. Dr. Kinrys has been a speaker for Astra-Zeneca, Forest Pharmaceuticals Inc., GlaxoSmithkline, Sepracor Inc., and Wyeth-Ayerst Laboratories.

Dr. Sylvia was a shareholder in Concordant Rater Systems and serves as a consultant for Bracket Global, Inc and Clintara. She also receives royalties from New Harbinger Publishers.

Dr. Friedman receives grant support from Repligen, Astra-Zeneca, Roche, Takeda, Neosync. He has been a consultant for Pamlab. He receives royalties from Springer. He has served as an expert forensic consultant for Thomson Rhodes & Cowie P.C. and Berger and Zavesky Co. L.P.A.

Dr. Kocsis has received research grants and contracts from AHRQ, NIMH, NIDA, Burroughs Wellcome Trust, Pritzker Consortium, Takeda, Forest, Astra Zeneca, Roche. He is on the speaker′s bureau at Pfizer and Merck and on the advisory board at Corcept.

Dr. Kemp serves on the speakers bureau for Pfizer and AstraZeneca, is a consultant for Bristol-Myers Squibb, Teva, Corcept, Janssen. His spouse is a minor stockholder for Sanofi and Abbott.

Dr. Shelton has served as a consultant to Bristol-Myers Squibb, Cyberonics, Inc., Elan, Corp., Eli Lilly and Company, Euthymics Bioscience, Forest Pharmaceuticals, Janssen Pharmaceutica, Medtronic, Inc., Otsuka Pharmaceuticals, Pamlab, Inc., Pfizer, Inc., Ridge Diagnostics, Takeda Pharmaceuticals. Dr. Shelton has received research grant support from Appian Labs, Bristol-Myers Squibb, Elan, Corp., Eli Lilly and Company, Euthymics Bioscience, Forest Pharmaceuticals, Janssen Pharmaceutica, Naurex, Inc., Novartis Pharmaceuticals, Otsuka Pharmaceuticals, Pamlab, Inc., Repligen, Corp., Ridge Diagnostics, St. Jude Medical, Inc., Takeda Pharmaceuticals.

Dr. McElroy is a consultant to or member of the scientific advisory boards of Alkermes, Bracket, Corcept, MedAvante, Shire, Sunovian, and Teva. She is a principal or co-investigator on studies sponsored by the Agency for Healthcare Research & Quality (AHRQ), Alkermes, AstraZeneca, Cephalon, Eli Lilly and Company, Forest, Marriott Foundation, National Institute of Mental Health, Orexigen Therapeutics, Inc., Pfizer, Shire, Takeda Pharmaceutical Company Ltd., and Transcept Pharmaceutical, Inc. She is also an inventor on United States Patent no. 6,323,236 B2, Use of Sulfamate Derivatives for Treating Impulse Control Disorders, and along with the patent′s assignee, University of Cincinnati, Cincinnati, Ohio, has received payments from Johnson & Johnson, which has exclusive rights under the patent.

Dr. Sylvia was a shareholder in Concordant Rater Systems and serves as a consultant for Bracket Global, Inc and Clintara. She also receives royalties from New Harbinger Publishers.

Dr. Kocsis has received research grants and contracts from AHRQ, NIMH, NIDA, Burroughs Wellcome Trust, Pritzker Consortium, Takeda, Forest, Astra Zeneca, Roche. He is on the speaker′s bureau at Pfizer and Merck and on the advisory board at Corcept.

Dr. McInnis has received grants for research support from NIMH, the Heinz C Prechter Research Fund, and the Michigan Institute for Clinical Health Research (MICHR). MM has received consulting income from the Qatar National Research Foundation and Merck Pharmaceuticals.

Dr. Freedman received grant support from NIMH, AHRQ, Novartis, St. Jude Medical, Medtronics, Repligen, Astra-Zeneca, Roche, and Takeda. He receives royalties from Springer. He has been a consultant for PamLab.

Dr. Singh has been a speaker for Merck and Sunovion. He has received research support from Novartis and Astra Zeneca.

Dr. Tohen was an employee of Lilly (1997 to 2008) and has received honoraria from or consulted for AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Lilly, Johnson & Johnson, Otsuka, Merck, Sunovion, Forest, Roche, Elan, Lundbeck, Teva, Pamlab, Wyeth and Wiley Publishing; his spouse is a full time employee and minor stockholder at Lilly.

Dr. Bowden is a research collaborator with Elan and a consultant with Teva, he has no participation with speaker bureaus, nor does he or his wife hold any equity position in any biomedical or pharmaceutical corporation.

Dr. Deckersbach has received research support from NIMH, NARSAD, TSA, OCF, Tufts University, NIH, NIA, Janssen Pharmaceuticals, the Forest Research Institute, Shire Development Inc., Medtronic, Cyberonics, Northstar. He has received honoraria, consultation fees and/or royalties from the following: Medacorp, MGH Psychiatry Academy, BrainCells Inc., Systems Research and Applications Corporation, Boston University, Tufts University, the Catalan Agency for Health Technology Assessment and Research, the National Association of Social Workers Massachusetts, the Massachusetts Medical Society, and Oxford University Press.

Dr. Calabrese receives federal funding from the Department of Defense, Health Resources Services Administration, and NIMH; he receives research funding or grants from the following private industries or nonprofit funds: Cleveland Foundation, NARSAD, and Stanley Medical Research Institute; he receives research grants from Abbott, AstraZeneca, Cephalon, GlaxoSmithKline, Janssen, Eli Lilly, and Lundbeck; he serves on the advisory boards of Abbott, AstraZeneca, Bristol-Myers Squibb, Dainippon Sumitomo Pharma, Forest, France Foundation, GlaxoSmithKline, Janssen, NeuroSearch, OrthoMcNeil, Repligen, Schering-Plough, Servier, Solvay/Wyeth, Takeda, and Supernus Pharmaceuticals; and he reports CME activities with AstraZeneca, Bristol-Myers Squibb, France Foundation, GlaxoSmithKline, Janssen, Johnson & Johnson, Schering-Plough, and Solvay/Wyeth.

Dr. Thase has been an advisor/consultant: to Alkermes, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Forest Laboratories, GlaxoSmithKline, Janssen Pharmaceuticals, Lundbeck, MedAvante, Merck, Mylan, Neuronetics, Otsuka, Pamlab, PharmaNeuroboost, Pfizer, Rexahn, Roche, Shire, Sunovion, Supernus, Takeda, and Teva, as well as the US Food and Drug Administration and the National Institute of Mental Health. During the same time frame, Dr. Thase has received honoraria for talks from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck, and Pfizer and he has received research grants from Alkermes, AstraZeneca, Eli Lilly, Forest, GlaxoSmithKline, Otsuka, PharmaNeuroboost, and Roche, as well as the National Institute of Mental Health and the Agency for Healthcare Research and Quality.

Dr. Nierenberg is a consultant for Abbott Laboratories, Astra Zeneca, Basilea, BrainCells Inc., Brandeis University, Bristol-Myers Squibb, Cephalon, Corcept, Eli Lilly & Co., Forest, Genaissance, GlaxoSmithKline, Innapharma, Janssen Pharmaceutica, Jazz Pharmaceuticals, Lundbeck, Merck, Novartis, PamLabs, PGx Health, Pfizer, Ridge Diagnostics, Roche, Sepracor, Schering-Plough, Shire, Somerset, Sunovion, Takeda, Targacept, and Teva. He is a stakeholder in Appliance Computing, Inc. (MindSite); Brain Cells, Inc., InfoMed (potential share of income). He receives research support from AHRQ, Bristol-Myers Squibb, Cederroth, Cyberonics, Elan, Forest Pharmaceuticals, GlaxoSmithKline, Janssen Pharmaceutica, Lichtwer Pharma, Eli Lilly, Mylin (formerly Dey Pharmaceuticals), NARSAD, NIMH, Pamlabs, Pfizer, Shire, Stanley Foundation, and Wyeth-Ayerst. Honoraria include MGH Psychiatry Academy in the past 3 years (Prior to 3 years ago, honoraria from Bristol-Myers Squibb, Cyberonics, Forest Pharmaceuticals, GlaxoSmithKline, Eli Lilly, Shire, Wyeth-Ayerst). Dr. Nierenberg receives other income from legal case reviews for CRICO, MBL Publishing for past services as Editor-in-chief of CNS Spectrums, Slack Inc. for services as Associate Editor of Psychiatric Annals, and Editorial Board, Mind Mood Memory, Belvior Publications. He has copyright joint ownership with MGH for Structured Clinical Interview for MADRS and Clinical Positive Affect Scale and additional honoraria from ADURS, American Society for Clinical Psychopharmacology and Zucker Hillside Hospital and Forest and Janssen, Biomedical Development, Boston Center for the Arts, University of Pisa, University of Wisconsin at Madison, University Texas Southwest at Dallas, Health New England and Harold Grinspoon Charitable Foundation and Eli Lilly and AstraZeneca, Brandeis University, International Society for Bipolar Disorder, 2nd East Asian Bipolar Forum, Mid-Atlantic Permanente Research Institute, Up-to-Date.

Mr. Rabideau reports no competing interests in the past three years.

Dr. Schoenfeld has an ongoing consulting relationship with the following pharmaceutical companies, Biogen, Neuronova, Cytokinetics, Edison Pharmaceuticals, Galaxo Smith Kine, Merck, Agennix, Alexion and Pfizer. He also has a consulting relationship with Aptiv a contract research organization.

Dr. Kamali reports no competing interests in the past three years.

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