BIPOLAR DEPRESSION A Comprehensive Guide This page intentionally left blank BIPOLAR DEPRESSION A Comprehensive Guide Edited by Rif S. El-Mallakh, M.D. S. Nassir Ghaemi, M.D., M.P.H. Washington, DC London, England Note: The authors have worked to ensure that all information in this book is accurate at the time of publication and consistent with general psychiatric and medical standards, and that information concerning drug dosages, schedules, and routes of administration is accurate at the time of publication and consis- tent with standards set by the U.S. Food and Drug Administration and the gen- eral medical community. As medical research and practice continue to advance, however, therapeutic standards may change. Moreover, specific situations may require a specific therapeutic response not included in this book. 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ALL RIGHTS RESERVED Manufactured in the United States of America on acid-free paper 100908070654321 First Edition Typeset in Adobe’s Palatino and Christiana American Psychiatric Publishing, Inc. 1000 Wilson Boulevard Arlington, VA 22209-3901 www.appi.org Library of Congress Cataloging-in-Publication Data Bipolar depression : a comprehensive guide / edited by Rif S. El-Mallakh, S. Nassir Ghaemi. — 1st ed. p. ; cm. Includes bibliographical references and index. ISBN 1-58562-171-4 (pbk. : alk. paper) 1. Manic-depressive illness. I. El-Mallakh, Rif S., 1956– . II. Ghaemi, S. Nassir. [DNLM: 1. Bipolar Disorder. WM 207 B6153 2006] RC516.B515 2006 616.89’5—dc22 2006001944 British Library Cataloguing in Publication Data A CIP record is available from the British Library. CONTENTS Contributors . vii DIAGNOSIS OF BIPOLAR DEPRESSION 1 Diagnosis of Bipolar Depression. 3 S. Nassir Ghaemi, M.D., M.P.H. Jaclyn Saggese, B.A. Frederick K. Goodwin, M.D. BIOLOGY OF BIPOLAR DEPRESSION 2 Neurobiology of Bipolar Depression . 37 Alan C. Swann, M.D. 3 Genetics of Bipolar Disorder . 69 Elizabeth P. Hayden, Ph.D. John I. Nurnberger Jr., M.D., Ph.D. SPECIAL TOPICS IN BIPOLAR DEPRESSION 4 Pediatric Bipolar Depression . 101 Anoop Karippot, M.D. 5 Suicide in Bipolar Depression . 117 Michael J. Ostacher, M.D., M.P.H. Polina Eidelman, B.A. TREATMENT AND PREVENTION OF BIPOLAR DEPRESSION 6 Lithium and Antiepileptic Drugs in Bipolar Depression . 147 Rif S. El-Mallakh, M.D. 7 Antidepressants in Bipolar Depression . .167 Rif S. EI-Mallakh, M.D. Anoop Karippot, M.D. S. Nassir Ghaemi, M.D., M.P.H. 8 Antipsychotics in Bipolar Depression . .185 Rif S. El-Mallakh, M.D. 9 Novel Treatments in Bipolar Depression . 191 Joseph Levine, M.D. Julia Appelbaum, M.D. RobertH. Belmaker, M.D. 10 Psychological Interventions in Bipolar Depression . 215 Francesc Colom, Psy.D., M.Sc., Ph.D. Eduard Vieta, M.D. 11 Future Directions for Practice and Research . .227 S. Nassir Ghaemi, M.D., M.P.H. Jacclyn Saggese, B.A. Frederick K. Goodwin, M.D. Index . .243 CONTRIBUTORS Julia Appelbaum, M.D. Stanley Research Center, Division of Psychiatry, Faculty of Health Sci- ences, Ben Gurion University of the Negev, Beer Sheva, Israel Robert H. Belmaker, M.D. Professor of Psychiatry, Faculty of Health Sciences, Ben Gurion Univer- sity of the Negev, Beer Sheva, Israel Polina Eidelman, B.A. Graduate Student, Massachusetts General Hospital, Boston, Massachu- setts Rif S. El-Mallakh, M.D. Director, Mood Disorders Research Program; Associate Professor, De- partment of Psychiatry and Behavioral Sciences, University of Louis- ville School of Medicine, Louisville, Kentucky S. Nassir Ghaemi, M.D., M.P.H. Associate Professor, Department of Psychiatry and Behavioral Sciences, Rollins School of Public Health; Director, Bipolar Disorder Research Program, Emory University, Atlanta, Georgia Frederick K. Goodwin, M.D. Center for Neuroscience, Medical Progress, and Society; Psychophar- macology Research Center; Research Professor, Department of Psychia- try and Behavioral Sciences, George Washington University, Washington, D.C. Elizabeth P. Hayden, Ph.D. Assistant Professor, Department of Psychology, University of Western Ontario, London, Ontario, Canada vii viii BIPOLAR DEPRESSION: A COMPREHENSIVE GUIDE Anoop Karippot, M.D. Assistant Professor, Division of Child and Adolescent Psychiatry, Bing- ham Child Guidance Center, University of Louisville School of Medi- cine, Louisville, Kentucky Joseph Levine, M.D. Associate Professor of Psychiatry, Stanley Research Center, Division of Psychiatry, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel John I. Nurnberger Jr., M.D., Ph.D. Joyce and Iver Small Professor of Psychiatry, Professor of Medical and Molecular Genetics, Institute of Psychiatric Research, Indiana Univer- sity School of Medicine, Indianapolis, Indiana Michael J. Ostacher, M.D., M.P.H. Associate Medical Director, Bipolar Clinic and Research Program, Mas- sachusetts General Hospital; Instructor, Harvard Medical School, Bos- ton, Massachusetts Jaclyn Saggese, B.A. Center for Neuroscience, Medical Progress, and Society; Psychophar- macology Research Center; Department of Psychiatry and Behavioral Sciences, George Washington University, Washington, D.C. Alan C. Swann, M.D. Pat R. Rutherford Jr. Professor and Vice Chair of Research, Department of Psychiatry and Behavioral Sciences, University of Texas Medical School, Houston, Texas Francesc Colom, Psy.D., M.Sc., Ph.D. Head of Psychoeducation and Psychological Treatment Areas, Bipolar Disorders Program, Stanley Research Center, University of Barcelona, Barcelona, Spain Eduard Vieta, M.D. Director of the Bipolar Disorders Program, Stanley Research Center, University of Barcelona, Barcelona, Spain DIAGNOSIS OF BIPOLAR DEPRESSION This page intentionally left blank 1 DIAGNOSIS OF BIPOLAR DEPRESSION S. Nassir Ghaemi, M.D., M.P.H. Jaclyn Saggese, B.A. Frederick K. Goodwin, M.D. ALTHOUGH DEPRESSION IS the most common presentation of bipolar disorder, a history of mania or hypomania is required for its diagnosis. Identifying these two behaviors defines the diagnostic problem that bi- polar depression represents: when faced with a depressed patient, it can be extremely difficult for the clinician to validate the depression as stemming from bipolar disorder. Generally speaking, determining that a patient currently meets cri- teria for a major depressive episode is straightforward. What is not straightforward, and therefore demands attention, is determining whether the patient’s history is consistent with unipolar or bipolar de- pression. We suggest here a hierarchical model for such a diagnostic as- sessment, based on the validators of diagnosis used in psychiatric nosology. THE VALIDATORS OF DIAGNOSIS The classic validators of psychiatric diagnoses were first discussed by Eli Robins and Samuel Guze in 1970 in reference to schizophrenia. They 3 4 BIPOLAR DEPRESSION: A COMPREHENSIVE GUIDE identified five validators: signs and symptoms, delimitation from other disorders, the follow-up study (outcome), family history, and labora- tory tests. The basic rationale for having multiple validators for a psy- chiatric diagnosis is the absence of a “gold standard.” Whereas in medicine clinicians often argue over a potential diagnosis only to have the pathologist declare the right answer, in psychiatry there is no such definitive and instantaneous resolution—psychiatry has no patholo- gist. (In fact, since many pathologists spent entire careers searching in vain for simple brain abnormalities in patients with schizophrenia, it had become something of a rueful joke to say that schizophrenia is the “graveyard of pathologists.”) In the absence of a specimen from an or- gan, psychiatric nosologists like Robins and Guze returned to the clas- sic work of Emil Kraepelin, who, noting the failures of neuropathology to reveal the causes of mental illness, emphasized that “diagnosis is prognosis” (Ghaemi 2003), by which he meant that a psychiatric diag- nosis is most clearly established by assessing the longitudinal course of illness. This perspective contrasts with the psychoanalytic tradition devel- oped in the United States and, to some extent, with the focus on phe- nomenology as it developed among some European scholars, such as Kurt Schneider (Janzarik 1998), for whom diagnosis was based substan- tially on the assessment of the patients’ current symptoms (Ghaemi 2003). Kraepelin’s approach argues that cross-sectional symptoms, no matter how well understood, are inadequate for diagnosing a disorder and that the course of illness is just as important, if not more so. Robins and Guze added the Kraepelinian criterion of course to the standard symptom-oriented approach to diagnosis in the United States. They further added the criteria of family history, in order to incorporate the influence of genetics, and laboratory tests, in the hopes for more ob- jective measures of illness. Since diagnostically useful laboratory tests have not been developed,