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Switching to Hypomania and Mania: Differential Neurochemical, Neuropsychological, and Pharmacologic Triggers and Their Mechanisms

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Abstract

Current data suggest that monoamines, acetylcholine, amino acids, cortisol, thyroid hormones, and melatonin may be involved in the pathophysiology of bipolar disorder (BPD). Any neuropsychological or pharmacologic factor causing a disturbance in these neurochemicals may trigger manic/hypomanic switching. Antidepressants, stimulants, anticholinergics, steroids, and thyroid hormone have been reported to cause treatment-emergent mania (TEM) in BPD, but only recently have the traditional antidepressants been systematically studied. Paroxetine, 20 mg/d, monotherapy in treatment of acute, relatively “pure” bipolar I and II depression, and fluoxetine monotherapy in bipolar II depression conferred a similar risk as placebo for TEM. Paroxetine or bupropion adjunctive therapy to mood stabilizer(s) had a similar risk as placebo for treatment of TEM in real world patients with bipolar depression during continuation treatment. Venlafaxine was shown to have an increased risk of TEM compared with bupropion and sertraline. The evolving literature continues to support the role of mood stabilizers in preventing future mood episodes of BPD.

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Acknowledgments

This work is supported by Research Fellowships of the World Psychiatric Association (Dr. Chen), the Shanghai Jiao-Tong University School of Medicine Natural Science Foundation (grant no. 09XJ21024 to Dr. Chen), the 10th Five-Year Plan of Chinese National Key Technologies Research and Development Program (grant no. 2004BA720A21-02 to Dr. Fang), Chinese National High-Tech Research and Development Program (grant no. 2006AA02Z430 to Dr. Fang), and Climbing Mountain Action Plan Program (grant no. 064119533 to Dr. Fang).

Dr. Kemp has received grant funding from the National Institutes of Health.

Dr. Calabrese has received federal funding from the Department of Defense, Health Resources Services Administration, and National Institute of Mental Health.

Disclosure

Dr. Kemp has served as a consultant for Bristol-Myers Squibb, on the speakers’ bureau for Pfizer and AstraZeneca, and has received grant funding from NARSAD and the Cleveland Foundation

Dr. Calabrese has received research support from Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Cephalon, the Cleveland Foundation, Eli Lilly and Company, GlaxoSmithKline, Janssen Pharmaceutica, NARSAD, Repligen Corp., the Stanley Medical Research Institute, Takeda Pharmaceuticals North America, and Wyeth; has served as a consultant or served on advisory boards for Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Cephalon, Dainippon Sumitomo Pharma, EPI-Q, Forest Laboratories, France Foundation, GlaxoSmithKline, Janssen Pharmaceutica, Johnson & Johnson, H. Lundbeck A/S, NeuroSearch A/S, Ortho-McNeil, Otsuka Pharmaceutical Group, Pfizer, Repligen Corp., Schering-Plough, Servier, Solvay Pharmaceuticals, Supernus Pharmaceuticals, Synosia Therapeutics, and Wyeth; has provided continuing medical education lectures supported by Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, the France Foundation, GlaxoSmithKline, Janssen Pharmaceutica, Johnson & Johnson, Sanofi-Aventis, Schering-Plough, Pfizer, Solvay Pharmaceuticals, and Wyeth; and has served on speakers’ bureaus for Abbott Laboratories, AstraZeneca, Eli Lilly and Company, and GlaxoSmithKline.

Dr. Gao has received research grants from AstraZeneca and NARSAD, has served on speakers’ bureaus for AstraZeneca and Pfizer, and has served as a consultant for Schering-Plough. Drs. Chen and Fang reported no potential conflicts of interest relevant to this article.

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Authors and Affiliations

  1. Department of Psychiatry, Case Western Reserve University School of Medicine, University Hospitals Case Medical Center, 10524 Euclid Avenue, 12th Floor, Cleveland, OH, 44106, USA

    Jun Chen, David E. Kemp, Joseph R. Calabrese & Keming Gao

  2. Shanghai Mental Health Center, Shanghai Jiao-Tong University School of Medicine, 600 South Wan Ping Road, Shanghai, 200030, China

    Jun Chen & Yiru Fang

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  1. Jun Chen
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  2. Yiru Fang
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  3. David E. Kemp
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  5. Keming Gao
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Correspondence to Yiru Fang or Keming Gao.

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Chen, J., Fang, Y., Kemp, D.E. et al. Switching to Hypomania and Mania: Differential Neurochemical, Neuropsychological, and Pharmacologic Triggers and Their Mechanisms. Curr Psychiatry Rep 12, 512–521 (2010). https://doi.org/10.1007/s11920-010-0157-z

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