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Reviews and Overviews   |    
The International Society for Bipolar Disorders (ISBD) Task Force Report on Antidepressant Use in Bipolar Disorders
Isabella Pacchiarotti, M.D., Ph.D.; David J. Bond, M.D., Ph.D.; Ross J. Baldessarini, M.D.; Willem A. Nolen, M.D., Ph.D.; Heinz Grunze, M.D.; Rasmus W. Licht, M.D., Ph.D.; Robert M. Post, M.D.; Michael Berk, M.D., Ph.D.; Guy M. Goodwin, F.Med.Sci.; Gary S. Sachs, M.D.; Leonardo Tondo, M.D.; Robert L. Findling, M.D.; Eric A. Youngstrom, Psy.D., Ph.D.; Mauricio Tohen, M.D., Dr.P.H.; Juan Undurraga, M.D.; Ana González-Pinto, M.D., Ph.D.; Joseph F. Goldberg, M.D.; Ayşegül Yildiz, M.D.; Lori L. Altshuler, M.D.; Joseph R. Calabrese, M.D.; Philip B. Mitchell, M.B.B.S., M.D.; Michael E. Thase, M.D.; Athanasios Koukopoulos, M.D.; Francesc Colom, Psy.D., Ph.D.; Mark A. Frye, M.D.; Gin S. Malhi, M.D.; Konstantinos N. Fountoulakis, M.D., Ph.D.; Gustavo Vázquez, M.D., Ph.D.; Roy H. Perlis, M.D.; Terence A. Ketter, M.D.; Frederick Cassidy, M.D.; Hagop Akiskal, M.D.; Jean-Michel Azorin, M.D.; Marc Valentí, M.D., Ph.D.; Diego Hidalgo Mazzei, M.D.; Beny Lafer, M.D.; Tadafumi Kato, M.D., Ph.D.; Lorenzo Mazzarini, M.D.; Anabel Martínez-Aran, Psy.D., Ph.D.; Gordon Parker, M.D., Ph.D.; Daniel Souery, M.D., Ph.D.; Ayşegül Özerdem, M.D., Ph.D.; Susan L. McElroy, M.D.; Paolo Girardi, M.D.; Michael Bauer, M.D., Ph.D.; Lakshmi N. Yatham, M.D.; Carlos A. Zarate, M.D.; Andrew A. Nierenberg, M.D.; Boris Birmaher, M.D.; Shigenobu Kanba, M.D., Ph.D.; Rif S. El-Mallakh, M.D.; Alessandro Serretti, M.D., Ph.D.; Zoltan Rihmer, M.D., Ph.D.; Allan H. Young, M.D., Ph.D.; Georgios D. Kotzalidis, M.D.; Glenda M. MacQueen, M.D., Ph.D.N.; Charles L. Bowden, M.D.; S. Nassir Ghaemi, M.D., M.P.H.; Carlos Lopez-Jaramillo, M.D., Ph.D.; Janusz Rybakowski, M.D., Ph.D.; Kyooseob Ha, M.D.; Giulio Perugi, M.D.; Siegfried Kasper, M.D.; Jay D. Amsterdam, M.D.; Robert M. Hirschfeld, M.D.; Flávio Kapczinski, M.D., Ph.D.; Eduard Vieta, M.D., Ph.D.
Am J Psychiatry 2013;170:1249-1262. doi:10.1176/appi.ajp.2013.13020185
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Dr. Bond has received honoraria from the Canadian Network for Mood and Anxiety Treatments, the Canadian Psychiatric Association, Pfizer, Sunovion, Bristol-Myers Squibb, Otsuka, AstraZeneca, and Janssen-Ortho; and has received research grants from the Canadian Institutes of Health Research, the UBC Institute of Mental Health/Coast Capital Depression Research Fund, and Pfizer. Dr. Nolen has received grants from the Netherlands Organization for Health Research and Development, the European Union, the Stanley Medical Research Institute, AstraZeneca, GlaxoSmithKline, and Wyeth and honoraria or speaking fees from AstraZeneca and Lundbeck. Dr. Grunze has received research support, consulting fees, or honoraria from AstraZeneca, Bristol-Myers Squibb, Desitin, Eli Lilly, Gedeon-Richter, Hoffmann-La Roche, Janssen-Cilag, Lundbeck, Merck, Otsuka, Sanofi-Aventis, Servier, Sepracor, and UBC. Dr. Licht has served on advisory boards for Bristol-Myers Squibb, AstraZeneca, and MSD and has received honoraria from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Lundbeck, and Pfizer. Dr. Post has served as a consultant or speaker for AstraZeneca, Sunovion, Teva, and Validas. Dr. Berk has received research support from or served as a consultant or speaker for AstraZeneca, Beyond Blue, Bristol-Myers Squibb, Cancer Council of Victoria, Cooperative Research Centre, Eli Lilly, Geelong Medical Research Foundation, GlaxoSmithKline, Janssen Cilag, Lundbeck, Mayne Pharma, MBF, Meat and Livestock Board, Merck, National Health and Medical Research Council (Australia), NIH, Novartis, Organon, Pfizer, Rotary Health, Sanofi Synthelabo, Servier, Simons Autism Foundation, Stanley Medical Research Foundation, Solvay, Woolworths, and Wyeth and is a co-inventor on two provisional patents regarding the use of N-acetylcysteine and related compounds for psychiatric indications. Dr. Goodwin has received grants from Bailly Thomas, Medical Research Council, National Institute for Health Research (U.K.), and Servier, has served as consultant, adviser, or CME speaker for AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, Cephalon/Teva Janssen-Cilag, Eli Lilly, Lundbeck, Otsuka, P1Vital, Roche, Servier, Schering-Plough, Shire, Sunovion, and Takeda, and holds shares in P1Vital. Dr. Sachs has served on advisory boards for Elan, Janssen, Merck, Otsuka, Roche, Sunovion, and Takeda. Dr. Findling has received research support or served as a consultant or speaker for Alexza Pharmaceuticals, American Psychiatric Publishing, AstraZeneca, Bracket, Bristol-Myers Squibb, Clinsys, Cognition Group, Forest, GlaxoSmithKline, Guilford Press, Johns Hopkins University Press, Johnson & Johnson, KemPharm, Lilly, Lundbeck, Merck, NIH, Novartis, Noven, Otsuka, Oxford University Press, Pfizer, Physicians Postgraduate Press, Rhodes Pharmaceuticals, Roche, Sage, Seaside Pharmaceuticals, Shire, Stanley Medical Research Institute, Sunovion, Supernus Pharmaceuticals, Transcept Pharmaceuticals, Validus, and WebMD. Dr. Youngstrom has served as a consultant for Lundbeck. Dr. Tohen has received honoraria from or served as a consultant for AstraZeneca, Bristol-Myers Squibb, Elan, Eli Lilly, Forest, GlaxoSmithKline, Johnson & Johnson, Lundbeck, Merck, Otsuka, PamLab, Roche, Sunovion, Teva, Wyeth, and Wiley Publishing; his spouse is an employee and stockholder at Eli Lilly. Dr. Gonzalez-Pinto has received grants from or served as consultant, adviser, or CME speaker for Almirall, AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Jazz, Johnson & Johnson, Lundbeck, Merck, Otsuka, Pfizer, Sanofi-Aventis, Servier, Schering-Plough, Solvay, the Spanish Ministry of Science and Innovation (CIBERSAM), the Ministry of Science (Carlos III Institute), the Basque Government, Stanley Medical Research Institute, and Wyeth. Dr. Goldberg has served as consultant or speaker for AstraZeneca, Grünenthal Group, Medscape, Merck, Mylan Pharmaceuticals, Novartis, Sunovion, and WebMD and receives royalties from American Psychiatric Publishing. Dr. Yildiz has received research grants from or served as a consultant or speaker for Abdi Ibrahim, Actavis, Ali Raif, AstraZeneca, Bristol-Myers Squibb, Janssen-Cilag, Lundbeck, Pfizer, Sanofi-Aventis, and Servier. Dr. Altshuler has served on advisory boards or as a consultant for Eli Lilly, Takeda Pharmaceuticals North America, Lundbeck, Sepracor, and Sunovion. Dr. Calabrese has received funding or research support from or served as a consultant or CME speaker or on advisory boards for Abbott, AstraZeneca, Bristol-Myers Squibb, Cephalon, Cleveland Foundation, Dainippon Sumitomo, Department of Defense, Eli Lilly, EPI-Q, Forest, France Foundation, GlaxoSmithKline, Health Resources Services Administration, Janssen, Johnson & Johnson, Lundbeck, Merck, NARSAD, Neurosearch, NIMH, Ortho-McNeil, Otsuka, Pfizer, Repligen, Sanofi-Aventis, Schering-Plough, Servier, Solvay, Stanley Medical Research Institute, Supernus, Synosia, Takeda, and Wyeth. Dr. Thase has received grant funding from or served as a consultant for Agency for Healthcare Research and Quality, Alkermes, Allergan, AstraZeneca, Bristol-Myers Squibb, Dey Pharma, Eli Lilly, Forest Laboratories, Forest Pharmaceuticals, Gerson Lehman Group, GlaxoSmithKline, Guidepoint Global, Lundbeck, MedAvante, Merck, NeoSync, Neuronetics, NIMH, Novartis, Otsuka, Ortho-McNeil Pharmaceuticals, PamLab, Pfizer (formerly Wyeth-Ayerst Laboratories), PharmaNeuroboost, Roche Laboratories, Shire US, Sunovion, Takeda, Teva, and Transcept; he receives royalties from American Psychiatric Foundation, Guilford Publications, Herald House, Oxford University Press, and W.W. Norton and has equity holdings in MedAvante; his wife is employed by Peloton Advantage, which does business with Pfizer. Dr. Colom has served as adviser or speaker for Adamed, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Lundbeck, MSD-Merck, Otsuka, Pfizer, Sanofi-Aventis, Shire, and Tecnifar and has received copyright fees from Cambridge University Press, Igaku-Shoin, Solal Ed., Ars Médica, Giovani Fioriti Ed., Medipage, La Esfera de Los Libros, Morales i Torres Ed, Panamericana, and Mayo Ed. & Columna. Dr. Frye has received grant support from the Mayo Foundation, Myriad, NARSAD, the National Institute of Alcohol Abuse and Alcoholism, NIMH, and Pfizer and travel support from Advanced Health Media, AstraZeneca, Bristol-Myers Squibb, Chilean Society of Neurology, Psychiatry, and Neurosurgery, Colombian Society of Neuropsychopharmacology, GlaxoSmithKline, Otsuka, and Sanofi-Aventis; he has served as an unpaid consultant for Allergan, Merck, Myriad, Sanofi-Aventis, Sunovion, Takeda Global Research, Teva Pharmaceuticals, and United Biosource Corporation. Dr. Malhi has received research support from or served as a speaker or consultant for AstraZeneca, Eli Lilly, Janssen-Cilag, Lundbeck, Organon, Pfizer, Ranbaxy, Servier, and Wyeth. Dr. Fountoulakis has received research support or travel support from or served as a speaker or consultant for AstraZeneca, Bristol-Myers Squibb, Janssen-Cilag, Eli Lilly, Pfizer Foundation, and Wyeth. Dr. Vazquez has served as consultant or speaker for AstraZeneca, Gador, GlaxoSmithKline, Ivax, Eli Lilly, Lundbeck, Pfizer, Raffo, Servier, and Novartis. Dr. Perlis has served on advisory boards or as a consultant for Genomind, Healthrageous, PamLab, Pfizer, Proteus Biomedical, and RIDVentures. Dr. Ketter has received research support from or served as a consultant or speaker for Abbott, Allergan, AstraZeneca, Avanir, Bristol-Myers Squibb, Cephalon, Eli Lilly, Forest Pharmaceuticals, GlaxoSmithKline, Janssen, Merck, Otsuka, Pfizer, Sunovion, and Teva; he receives royalties from American Psychiatric Publishing, and his spouse is an employee of and holds stock in Janssen Pharmaceuticals. Dr. Akiskal receives honoraria or fees from Journal of Affective Disorders, AstraZeneca, University of Lisbon, Aristotle University of Thesaloniki, Sanofi, Nevada Psychiatric Association, and Medical Education Speakers Network. Dr. Azorin has received grants from Eli Lilly and Sanofi and honoraria from AstraZeneca, Bristol-Myers Squibb, Lundbeck Servier, and Eli Lilly; he has served on advisory boards for Eli Lilly, Lundbeck, Bristol-Myers Squibb, and Roche and as an expert witness for Eli Lilly. Dr. Lafer has received grant or research support from Brazilian research agencies CAPES (Coordination for the Improvement of Higher Education Personnel), FAPESP (São Paulo Research Foundation), and CNPq (National Council for Scientific and Technological Development). Dr. Kato has received research support from Takeda and honoraria for lectures, manuscripts, or consultancy from Kyowa Hakko Kirin, Eli Lilly Japan, Otsuka, GlaxoSmithKline, Taisho Toyama Pharmaceutical, Dainippon Sumitomo, Meiji Seika Pharma, Pfizer Japan, Mochida Pharmaceutical, Shionogi, Janssen, and Astellas. Dr. Martinez-Aran has served as speaker or adviser for Bristol-Myers Squibb, Lundbeck, Otsuka, and Pfizer. Dr. Parker has served as a speaker or on advisory boards for or received travel or speaking fees from AstraZeneca, Eli Lilly, Lundbeck, Pfizer, and Servier. Dr. Souery has served on advisory boards for AstraZeneca and Lundbeck and has received unrestricted grants for clinical research and educational activities from AstraZeneca, GlaxoSmithKline, and Lundbeck. Dr. Ozerdem has received honoraria or travel support from Abdi Ibrahim, Adeka, AstraZeneca, Bristol-Myers Squibb, EGIS, GlaxoSmithKline, Lundbeck, Nobel, Pfizer, Schering-Plough, and Servier. Dr. McElroy has served as a consultant for or on scientific advisory boards for Alkermes, Bracket, Corcept, MedAvante, Shire, Sunovion, and Teva; she is a principal or co-investigator on studies sponsored by the Agency for Healthcare Research and Quality, Alkermes, AstraZeneca, Cephalon, Eli Lilly, Forest, Marriott Foundation, NIMH, Orexigen Therapeutics, Pfizer, Shire, Takeda, and Transcept; she is also an inventor on a patent for use of sulfamate derivatives for treating impulse control disorders. Dr. Girardi has received research support from, served on advisory boards for, and received honoraria from Eli Lilly, Janssen, Otsuka, Pfizer, Schering, and Springer Healthcare. Dr. Bauer has received research support from or served as a consultant or speaker for Alkermes, American Foundation for Suicide Prevention, AstraZeneca, Bristol-Myers Squibb, Bundesministerium für Bildung und Forschung, Deutsche Forschungsgemeinschaft, European Commission (FP7), Ferrer Internacional, GlaxoSmithKline, Janssen, Eli Lilly, Lundbeck, NARSAD, Otsuka, Pfizer, Servier, Stanley Medical Research Institute, and Takeda. Dr. Yatham has received research support from or served as a speaker or advisory board member for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Janssen, GlaxoSmithKline, Lundbeck, Novartis, Pfizer, Servier, and Sunovion. Dr. Zarate is listed as a co-inventor on a patent application for the use of ketamine and its metabolites in major depression. Dr. Nierenberg has received research support from, served as a consultant for, or received honoraria from Abbott Laboratories, Agency for Healthcare Research and Quality, American Drug Utilization Review Society, American Society for Clinical Psychopharmacology, AstraZeneca, Basilea, Biomedical Development, Boston Center for the Arts, BrainCells, Brandeis University, Bristol-Myers Squibb, Cederroth, Cephalon, Corcept, Cyberonics, East Asian Bipolar Forum, Elan, Eli Lilly, Forest, Genaissance, GlaxoSmithKline, Harold Grinspoon Charitable Foundation, Health New England, Innapharma, International Society for Bipolar Disorder, Janssen, Jazz Pharmaceuticals, Lichtwer Pharma, Lundbeck, Merck, MGH Psychiatry Academy, Mid-Atlantic Permanente Research Institute, Mylan (formerly Dey Pharmaceuticals), NARSAD, NIMH, Novartis, PamLab, Pfizer, PGx Health, Ridge Diagnostics, Roche, Sepracor, Schering-Plough, Shire, Somerset, Stanley Foundation, Sunovion, Takeda, Targacept, Teva, University of Pisa, University of Wisconsin at Madison, University of Texas Southwestern Medical Center at Dallas, Wyeth-Ayerst, and Zucker Hillside Hospital; he 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 from Belvoir Publications for serving on the editorial board of Mind, Mood, and Memory; he has copyright joint ownership with MGH for the Structured Clinical Interview for MADRS and Clinical Positive Affect Scale and is a stakeholder in Appliance Computing (MindSite), Brain Cells, and InfoMed. Dr. Birmaher has received research support from NIMH and royalties from Random House, Lippincott Williams & Wilkins, and UpToDate. Dr. Kanba has received research support or honoraria from Astellas, Dainippon Sumitomo, Eisai, Eli Lilly Japan, GlaxoSmithKline, Janssen, Kyowa Hakko Kirin, Meiji Seika Pharma, MSD, Ono, Otsuka, Pfizer, Shionogi, Taisho Toyama, Wyeth, and Yoshitomiyakuhin. Dr. El-Mallakh has received research support from Merck and has served as a speaker for AstraZeneca and Otsuka. Dr. Serretti has served as a consultant or speaker for Abbott, Angelini, AstraZeneca, Bristol-Myers Squibb, Boehringer, Clinical Data, Eli Lilly, GlaxoSmithKline, Italfarmaco, Janssen, Lundbeck, Pfizer, Sanofi, and Servier. Dr. MacQueen has received research support from AstraZeneca and served as a consultant or speaker for Bristol-Myers Squibb, Canadian Psychiatric Association, Eli Lilly, Lundbeck, Norlien Foundation, Pfizer, Sanofi, and Servier. Dr. Bowden has received grant support from Novartis. Dr. Ghaemi has received research support from Takeda and has served as a consultant for Sunovion. Dr. Lopez-Jaramillo has received research support from Janssen Cilag, Lundbeck, NIH, Novartis, Pfizer, and University of Antioquia and honoraria from Abbott, GlaxoSmithKline, Eli Lilly, Lundbeck, Pfizer, Sanofi, and Servier. Dr. Ha has received research support or honoraria from AstraZeneca, Eli Lilly, Pfizer, and Otsuka. Dr. Perugi has received research support from or served as a consultant, speaker, or advisory board member for AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen-Cilag, Lundbeck, and Sanofi-Aventis. Dr. Kasper has received research support from or served as a consultant, speaker, or advisory board member for Angelini, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Lundbeck, MSD, Neuraxpharm, Novartis, Organon, Pfizer, Pierre Fabre, Schwabe, Sepracor, and Servier. Dr. Hirschfeld has served as a consultant for or received honoraria from American College of Psychiatrists, Biostrategies, Brown University, CME Alliance, CME Outfitters, Equinox Group, Grey Healthcare, Letters & Sciences, Merck Manual Editorial Board, Nevada Psychiatric Association, and Physicians Post Graduate Press Health and Wellness Partners and receives royalties from Jones & Bartlett and Taylor & Francis. Dr. Kapczinski has received research support from or served as a consultant or speaker for AstraZeneca, CNPq, CAPES, Eli Lilly, Janssen, Janssen-Cilag, NARSAD, Stanley Medical Research Institute, and Servier. Dr. Vieta has received research support from or served as consultant, adviser, or speaker for Alexza, Almirall, AstraZeneca, Bristol-Myers Squibb, Elan, Eli Lilly, Ferrer, Forest Research Institute, 7th Framework Program of the European Union, Geodon Richter, GlaxoSmithKline, Janssen-Cilag, Jazz, Lundbeck, Merck, Novartis, Organon, Otsuka, Pfizer, Roche, Sanofi-Aventis, Servier, Solvay, Schering-Plough, Shire, Spanish Ministry of Science and Innovation, Stanley Medical Research Institute, Takeda, Teva, United Biosource Corporation, and Wyeth. The remaining authors report no competing interests.

Dr. Koukopoulos died in April 2013.

From the Bipolar Disorders Program, Clinical Institute of Neuroscience, Hospital Clinic Barcelona, IDIBAPS (Institute of Biomedical Research August Pi i Sunyer), CIBERSAM (Center for Biomedical Research Network on Mental Health), University of Barcelona, Barcelona, Spain; Mood Disorders Centre, Department of Psychiatry, University of British Columbia, Vancouver; Department of Psychiatry, Harvard Medical School, Boston; Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, U.K.; Mood Disorders Research Unit, Aarhus University Hospital, Risskov, Denmark; Bipolar Collaborative Network, Bethesda, Md.; School of Medicine, Deakin University, Geelong, Australia; University Department of Psychiatry, Warneford Hospital, Oxford, U.K.; Bipolar Clinic and Research Program, Massachusetts General Hospital, Boston; Department of Psychiatry, Harvard Medical School, Boston; Lucio Bini Mood Disorder Center, Cagliari, Italy; Division of Child and Adolescent Psychiatry, Case Western Reserve University School of Medicine, Cleveland; Johns Hopkins Children’s Center, Baltimore; Department of Psychology, University of North Carolina, Chapel Hill; Department of Psychiatry, School of Medicine, University of New Mexico, Albuquerque; Department of Psychiatry, Santiago Apóstol Hospital, University of the Basque Country, CIBERSAM, Vitoria, Spain; Department of Psychiatry, Mount Sinai School of Medicine, New York; Department of Psychiatry and Department of Neurosciences, Dokuz Eylül Üniversitesi, Izmir, Turkey; Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California, Los Angeles; University of New South Wales School of Psychiatry and Black Dog Institute, Prince of Wales Hospital, Randwick, New South Wales, Australia; Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia; Philadelphia Veterans Affairs Medical Center, Philadelphia; Centro Lucio Bini, Rome; Departments of Psychiatry and Psychology, Integrated Mood Group, Mayo Clinic, Rochester, Minn.; CADE Clinic, Discipline of Psychiatry, University of Sydney, Sydney, Australia; 3rd Department of Psychiatry, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece; Department of Neuroscience, Palermo University, Buenos Aires, Argentina; Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford; Duke University Medical Center, Durham, N.C.; International Mood Center, University of California at San Diego, La Jolla, Calif.; Hôpital Sainte Marguerite, Marseille, France; Bipolar Research Program, Department and Institute of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil; Laboratory for Molecular Dynamics of Mental Disorders, RIKEN Brain Science Institute, Saitama, Japan; Sapienza University–Rome, School of Medicine and Psychology, NESMOS Department, Sant’Andrea Hospital, Rome; Laboratory of Medical Psychology, Free University of Brussels and “Psy Pluriel,” European Center for Medical Psychology, Brussels; University of Cincinnati College of Medicine, Psychiatry and Behavioral Neuroscience, Cincinnati; Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität Dresden, Germany; NIMH, Bethesda, Md.; Department of Psychiatry, Western Psychiatric Institute and Clinic, Pittsburgh; Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; University of Louisville, Louisville, Ky.; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; Department of Clinical and Theoretical Mental Health, Semmelweis University, Budapest, Hungary; Imperial College, London; Department of Psychiatry, University Calgary, Calgary, Canada; Department of Psychiatry, University of Texas Health Science Center at San Antonio; Mood Disorders Program, Department of Psychiatry, Tufts Medical Center, Tufts University School of Medicine, Boston; Mood Disorders Program, Fundacion San Vicente de Paul, Department of Psychiatry, Universidad de Antioquia, Medellín, Colombia; Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland; Mood Disorders Clinic and Clinical Affective Neuroscience Laboratory, Department of Psychiatry, Seoul National University Bundang Hospital, Bundang, Republic of Korea; Department of Psychiatry, University of Pisa, Pisa, Italy; Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna; Depression Research Unit, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia; Department of Psychiatry and Behavioral Sciences, University of Texas Medical Branch, Galveston; and Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.

Address correspondence to Dr. Vieta (evieta@clinic.ub.es).

Copyright © 2013 by the American Psychiatric Association

Received February 11, 2013; Revised May 24, 2013; Accepted June 03, 2013.

Abstract

Objective  The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders.

Method  An expert task force iteratively developed consensus through serial consensus-based revisions using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new or reworded items and items that needed to be rerated. This process resulted in the final ISBD Task Force clinical recommendations on antidepressant use in bipolar disorder.

Results  There is striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder. Few well-designed, long-term trials of prophylactic benefits have been conducted, and there is insufficient evidence for treatment benefits with antidepressants combined with mood stabilizers. A major concern is the risk for mood switch to hypomania, mania, and mixed states. Integrating the evidence and the experience of the task force members, a consensus was reached on 12 statements on the use of antidepressants in bipolar disorder.

Conclusions  Because of limited data, the task force could not make broad statements endorsing antidepressant use but acknowledged that individual bipolar patients may benefit from antidepressants. Regarding safety, serotonin reuptake inhibitors and bupropion may have lower rates of manic switch than tricyclic and tetracyclic antidepressants and norepinephrine-serotonin reuptake inhibitors. The frequency and severity of antidepressant-associated mood elevations appear to be greater in bipolar I than bipolar II disorder. Hence, in bipolar I patients antidepressants should be prescribed only as an adjunct to mood-stabilizing medications.

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FIGURE 1. Flow Diagram of Study Design and Results in a Review of Antidepressant Use in Bipolar Disorders

a Criteria for clinical response or remission were based on international standards, typically involving a decrease of ≥50% from baseline to a final score on a standard symptom rating scale (response) and a final depression score ≤7 (typically using the 17-item Hamilton Depression Rating Scale).

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TABLE 1.Summary of Average Quality and Evidence Level of Studies for Each Topic Addressed in a Review of Antidepressant Use in Bipolar Disordersa
Table Footer Note

a The Jadad score is an indicator of study methodological quality (ranging from 0 to 5, with higher scores indicating higher quality). The grades for evidence level, which also reflect study quality, run from A (excellent) to D (poor). See the online data supplement.

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TABLE 2.International Society for Bipolar Disorders Clinical (ISBD) Recommendations for Antidepressant Use in Bipolar Disordersa
Table Footer Note

a From an initial 25 items in six domains, the 12 presented here were rated by at least 80% of ISBD experts as essential or important and were included in the ISBD recommendations.

+

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