Treatment-emergent mania/hypomania during antidepressant monotherapy in patients with rapid cycling bipolar disorder

Authors

  • Keming Gao,

    1. Department of Psychiatry, Bipolar Disorder Research Center at Mood Disorders Program, Case Western Reserve University School of Medicine, University Hospitals Case Medical Center
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  • David E Kemp,

    1. Department of Psychiatry, Bipolar Disorder Research Center at Mood Disorders Program, Case Western Reserve University School of Medicine, University Hospitals Case Medical Center
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  • Stephen J Ganocy,

    1. Department of Psychiatry, Bipolar Disorder Research Center at Mood Disorders Program, Case Western Reserve University School of Medicine, University Hospitals Case Medical Center
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  • David J Muzina,

    1. Neurology Institute/Psychiatry and Psychology, Cleveland Clinic Lerner College of Medicine at Case Western Reserve University, Cleveland, OH
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  • Guohua Xia,

    1. Department of Psychiatry, Bipolar Disorder Research Center at Mood Disorders Program, Case Western Reserve University School of Medicine, University Hospitals Case Medical Center
    2. Present address: Department of Psychiatry, University of California Davis Medical Center, Sacramento, CA, USA
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  • Robert L Findling,

    1. Department of Psychiatry, Bipolar Disorder Research Center at Mood Disorders Program, Case Western Reserve University School of Medicine, University Hospitals Case Medical Center
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  • Joseph R Calabrese

    1. Department of Psychiatry, Bipolar Disorder Research Center at Mood Disorders Program, Case Western Reserve University School of Medicine, University Hospitals Case Medical Center
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  • KG has received grant support from Abbott, AstraZeneca, GlaxoSmithKline, and NARSAD, and has acted as a consultant and served on the speakers bureau for AstraZeneca. DEK has acted as a consultant for Abbott, Bristol-Myers Squibb, and Wyeth; has received honoraria from Servier; and is supported in part by NIH grant 1KL2RR024990. DJM has received grant support and/or honoraria from Abbott, AstraZeneca, Pfizer, GlaxoSmithKline, Eli Lilly & Co., and Repligen. GX has received research funding from NARSAD. RLF receives or has received research support, acted as a consultant and/or served on the speakers bureau for Abbott, AstraZeneca, Bristol-Myers Squibb, Cypress Biosciences, Forest, GlaxoSmithKline, Johnson & Johnson, Eli Lilly & Co., Neuropharm, New River, Novartis, Organon, Otsuka, Pfizer, Sanofi-Aventis, Sepracore, Shire, Solvay, Supernus Pharmaceuticals, and Wyeth. JRC has received grant support and/or honoraria from Abbott, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Eli Lilly & Co., Pfizer, and Janssen. SJG has no reported conflict of interest.

Keming Gao, M.D., Ph.D., Department of Psychiatry, Case Western Reserve University School of Medicine, University Hospitals Case Medical Center, 10524 Euclid Avenue, 12th Floor, Cleveland, OH 44106, USA. Fax: 1 216 844 2875; e-mail: keming.gao@uhhospitals.org

Abstract

Objective:  To study treatment-emergent mania/hypomania (TEM) associated with second-generation antidepressant monotherapy in patients with rapid cycling bipolar disorder (RCBD).

Methods:  Data of patients with RCBD (n = 180) enrolled into two clinical trials were used to study the risk for TEM during second-generation antidepressant monotherapy. History of TEM was retrospectively determined at the initial assessment by asking patients whether they were exposed to second-generation antidepressants and if a hypomania/mania episode emerged during the first four weeks of treatment. Data were analyzed using t-test, chi-square, and logistic regression.

Results:  Of the 180 patients (bipolar I disorder, n = 128; bipolar II disorder, n = 52) with RCBD, 85% (n = 153) had at least one antidepressant treatment. Among these patients, 94.1% (144/153) had at least one antidepressant monotherapy treatment. Overall, 49.3% of patients had at least one TEM and 29.1% (116/399) of treatment trials were associated with TEM. In regression analysis, an inverse association between the number of mood episodes in the last 12 months and TEM was observed with an odds ratio of 0.9. However, gender, bipolar subtype, a lifetime history of comorbid anxiety disorder, substance use disorder, or psychosis, and age of mood disorder onset were not associated with TEM. For individual antidepressants, the rates of TEM varied from 42.1% for fluoxetine to 0% for fluvoxamine and mirtazapine. As a group, there was no difference between selective serotonin reuptake inhibitors and venlafaxine or bupropion in the incidence of TEM.

Conclusions:  Use of second-generation antidepressants as monotherapy in RCBD is accompanied by clinically relevant rates of TEM. Even in patients with RCBD, differential vulnerabilities to antidepressant TEM may exist.

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