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Published Online: 1 January 2013

Bipolar Mixed States: An International Society for Bipolar Disorders Task Force Report of Symptom Structure, Course of Illness, and Diagnosis

Abstract

Objective

Episodes of bipolar disorder are defined as depressive or manic, but depressive and manic symptoms can combine in the same episode. Coexistence or rapid alternation of depressive and manic symptoms in the same episode may indicate a more severe form of bipolar disorder and may pose diagnostic and treatment challenges. However, definitions of mixed states, especially those with prominent depression, are not well established.

Method

The authors performed literature searches for bipolar disorder, multivariate analyses, and the appearance of the terms “mixed” in any field; references selected from the articles found after the search were combined after a series of conferences among the authors.

Results

The authors reviewed the evolution of the concept of mixed states and examined the symptom structure of mixed states studied as predominantly manic, predominantly depressive, and across both manic and depressive episodes, showing essentially parallel structures of mixed states based on manic or depressive episodes. The authors analyzed the relationships between mixed states and a severely recurrent course of illness in bipolar disorder, with early onset and increased co-occurring anxiety-, stress-, and substance-related disorders, and they used this information to derive proposed diagnostic criteria for research or clinical use.

Conclusions

The definitions and properties of mixed states have generated controversy, but the stability of their characteristics over a range of clinical definitions and diagnostic methods shows that the concept of mixed states is robust. Distinct characteristics related to the course of illness emerge at relatively modest opposite polarity symptom levels in depressive or manic episodes.

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Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 31 - 42
PubMed: 23223893

History

Received: 4 March 2012
Revision received: 29 April 2012
Accepted: 10 May 2012
Published online: 1 January 2013
Published in print: January 2013

Authors

Affiliations

Alan C. Swann, M.D.
From the Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston; the Department of Psychiatry, Bipolar Disorder Research Program, Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, University of Pisa, Pisa, Italy; the G. De Lisio Institute of Behavioral Sciences, Pisa; the Mayo Clinic, Rochester, Minn.; the Department of Psychiatry and Psychotherapy, University Hospital, Carl Gustav Carus Technical University, Dresden, Germany; the Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul; the Institute of Neuroscience, Newcastle University, U.K.; University of Paris East, Creteil, France; the Translational Research Center and Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; and VA Palo Alto Health Care System, Palo Alto, Calif.
Beny Lafer, M.D.
From the Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston; the Department of Psychiatry, Bipolar Disorder Research Program, Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, University of Pisa, Pisa, Italy; the G. De Lisio Institute of Behavioral Sciences, Pisa; the Mayo Clinic, Rochester, Minn.; the Department of Psychiatry and Psychotherapy, University Hospital, Carl Gustav Carus Technical University, Dresden, Germany; the Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul; the Institute of Neuroscience, Newcastle University, U.K.; University of Paris East, Creteil, France; the Translational Research Center and Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; and VA Palo Alto Health Care System, Palo Alto, Calif.
Giulio Perugi, M.D.
From the Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston; the Department of Psychiatry, Bipolar Disorder Research Program, Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, University of Pisa, Pisa, Italy; the G. De Lisio Institute of Behavioral Sciences, Pisa; the Mayo Clinic, Rochester, Minn.; the Department of Psychiatry and Psychotherapy, University Hospital, Carl Gustav Carus Technical University, Dresden, Germany; the Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul; the Institute of Neuroscience, Newcastle University, U.K.; University of Paris East, Creteil, France; the Translational Research Center and Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; and VA Palo Alto Health Care System, Palo Alto, Calif.
Mark A. Frye, M.D.
From the Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston; the Department of Psychiatry, Bipolar Disorder Research Program, Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, University of Pisa, Pisa, Italy; the G. De Lisio Institute of Behavioral Sciences, Pisa; the Mayo Clinic, Rochester, Minn.; the Department of Psychiatry and Psychotherapy, University Hospital, Carl Gustav Carus Technical University, Dresden, Germany; the Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul; the Institute of Neuroscience, Newcastle University, U.K.; University of Paris East, Creteil, France; the Translational Research Center and Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; and VA Palo Alto Health Care System, Palo Alto, Calif.
Michael Bauer, M.D.
From the Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston; the Department of Psychiatry, Bipolar Disorder Research Program, Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, University of Pisa, Pisa, Italy; the G. De Lisio Institute of Behavioral Sciences, Pisa; the Mayo Clinic, Rochester, Minn.; the Department of Psychiatry and Psychotherapy, University Hospital, Carl Gustav Carus Technical University, Dresden, Germany; the Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul; the Institute of Neuroscience, Newcastle University, U.K.; University of Paris East, Creteil, France; the Translational Research Center and Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; and VA Palo Alto Health Care System, Palo Alto, Calif.
Won-Myong Bahk, M.D.
From the Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston; the Department of Psychiatry, Bipolar Disorder Research Program, Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, University of Pisa, Pisa, Italy; the G. De Lisio Institute of Behavioral Sciences, Pisa; the Mayo Clinic, Rochester, Minn.; the Department of Psychiatry and Psychotherapy, University Hospital, Carl Gustav Carus Technical University, Dresden, Germany; the Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul; the Institute of Neuroscience, Newcastle University, U.K.; University of Paris East, Creteil, France; the Translational Research Center and Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; and VA Palo Alto Health Care System, Palo Alto, Calif.
Jan Scott, M.D.
From the Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston; the Department of Psychiatry, Bipolar Disorder Research Program, Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, University of Pisa, Pisa, Italy; the G. De Lisio Institute of Behavioral Sciences, Pisa; the Mayo Clinic, Rochester, Minn.; the Department of Psychiatry and Psychotherapy, University Hospital, Carl Gustav Carus Technical University, Dresden, Germany; the Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul; the Institute of Neuroscience, Newcastle University, U.K.; University of Paris East, Creteil, France; the Translational Research Center and Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; and VA Palo Alto Health Care System, Palo Alto, Calif.
Kyooseob Ha, M.D.
From the Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston; the Department of Psychiatry, Bipolar Disorder Research Program, Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, University of Pisa, Pisa, Italy; the G. De Lisio Institute of Behavioral Sciences, Pisa; the Mayo Clinic, Rochester, Minn.; the Department of Psychiatry and Psychotherapy, University Hospital, Carl Gustav Carus Technical University, Dresden, Germany; the Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul; the Institute of Neuroscience, Newcastle University, U.K.; University of Paris East, Creteil, France; the Translational Research Center and Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; and VA Palo Alto Health Care System, Palo Alto, Calif.
Trisha Suppes, M.D., Ph.D.
From the Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston; the Department of Psychiatry, Bipolar Disorder Research Program, Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Department of Psychiatry, University of Pisa, Pisa, Italy; the G. De Lisio Institute of Behavioral Sciences, Pisa; the Mayo Clinic, Rochester, Minn.; the Department of Psychiatry and Psychotherapy, University Hospital, Carl Gustav Carus Technical University, Dresden, Germany; the Department of Psychiatry, College of Medicine, The Catholic University of Korea, Seoul; the Institute of Neuroscience, Newcastle University, U.K.; University of Paris East, Creteil, France; the Translational Research Center and Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea; the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif.; and VA Palo Alto Health Care System, Palo Alto, Calif.

Notes

Address correspondence to Dr. Swann ([email protected]).

Funding Information

Dr. Swann is a consultant for Merck; is a speaker for Abbott Laboratories, AstraZeneca, Merck, and Sanofi-Aventis; and is on data safety and monitoring boards for Cephalon and Pfizer. Prof. Perugi has received consulting fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, and Sanofi-Aventis; has received research support from AstraZeneca, Boehringer Ingheleim, Eli Lilly, GlaxoSmith Kline; is on the speakers/advisory boards of AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Jannsen-Cilag, Lundbeck, Pfizer, Sanofi Aventis, and Wyeth. Dr. Frye receives grant support from the Mayo Foundation, Myriad, NARSAD, NIMH, National Institute of Alcohol Abuse and Alcoholism, and Pfizer. Dr. Bauer receives advisory board fees from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Jannssen-Cilag, Lundbeck, Otsuka, and Servier and receives honoraria from AstraZeneca, Eli Lilly, Servier, Lundbeck, Bristol-Myers Squibb, Otsuka, Pfizer, and GlaxoSmithKline. Dr. Scott is supported by Fondation FondaMental and has received funding from the Medical Research Council UK BP II Cohort Study, NHS UK Research for Patient Benefit, NHS UK Service Delivery and Organization Program, NTW FSF Research Fund, and the Jansen-Cilag Unrestricted Educational Grant; she has received conference travel funding, speaking fees, or advisory board fees from AstraZeneca, Bristol-Myers Squibb-Otsuka, Eli Lilly, GlaxoSmithKline, Jansen-Cilag, Lundbeck, Sanofi-Aventis, and Servier. Dr. Ha has received research support from AstraZeneca, Eli Lilly, Otsuka, and Pfizer and has received honoraria from AstraZeneca, GlaxoSmithKline, Otsuka, and Pfizer. Dr. Suppes has received funding or medications for clinical grants from AstraZeneca, NIMH, Pfizer, and Sunovion Pharmaceuticals and has received royalties from Jones and Bartlett (formerly Compact Clinicals). Dr. Lafer and Dr. Bahk report no financial relationships with commercial interests.

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