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THE EVIDENCE-BASED GUIDE TO
ANTIPSYCHOTIC
MEDICATIONS
This page intentionally left blank
THE EVIDENCE-BASED GUIDE TO
ANTIPSYCHOTIC
MEDICATIONS

Edited by

Anthony J. Rothschild, M.D.

Irving S. and Betty Brudnick Endowed Chair and
Professor of Psychiatry, Department of Psychiatry
University of Massachusetts Medical School
UMass Memorial Healthcare
Worcester, Massachusetts

Washington, DC
London, England
Note: The authors have worked to ensure that all information in this book is accu-
rate 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 consistent with standards
set by the U.S. Food and Drug Administration and the general medical community. As
medical research and practice continue to advance, however, therapeutic standards
may change. Moreover, specific situations may require a specific therapeutic re-
sponse not included in this book. For these reasons and because human and mechan-
ical errors sometimes occur, we recommend that readers follow the advice of
physicians directly involved in their care or the care of a member of their family.
Books published by American Psychiatric Publishing, Inc., represent the views and
opinions of the individual authors and do not necessarily represent the policies and
opinions of APPI or the American Psychiatric Association.
If you would like to buy between 25 and 99 copies of this or any other APPI title, you
are eligible for a 20% discount; please contact APPI Customer Service at ap-
[email protected] or 800-368-5777. If you wish to buy 100 or more copies of the same ti-
tle, please e-mail us at [email protected] for a price quote.
Copyright © 2010 American Psychiatric Publishing, Inc.
ALL RIGHTS RESERVED
Manufactured in the United States of America on acid-free paper
13 12 11 10 09 5 4 3 2 1
First Edition
Typeset in Adobe’s Cushing and Optima
American Psychiatric Publishing, Inc.
1000 Wilson Boulevard Cert no. XXX-XXX-XXXX

Arlington, VA 22209–3901
www.appi.org
Library of Congress Cataloging-in-Publication Data
The evidence-based guide to antipsychotic medications / edited by Anthony J.
Rothschild. — 1st ed.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-58562-366-2 (pbk. : alk. paper)
1. Antipsychotic drugs. 2. Evidence-based psychiatry. I. Rothschild, Anthony J.
[DNLM: 1. Mental Disorders—drug therapy. 2. Antipsychotic Agents—therapeutic
use. 3. Evidence-Based Medicine. WM 402 E945 2010]
RM333.5.E95 2010
615′.7882–dc22
2009040345
British Library Cataloguing in Publication Data
A CIP record is available from the British Library.
To Judy, Rachel, and Amanda; my mother, Edith Rothschild,
and the memory of my father, Ernest Rothschild; and the
memory of my in-laws, Maye and Arnold Shindul.

The book is also dedicated to Betty Brudnick and in memory

of Irving Brudnick, without whose generous support this book
would not have been possible.
This page intentionally left blank
Contents

Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . xiii
Acknowledgments . . . . . . . . . . . . . . . . . . . . xvii
Disclaimer . . . . . . . . . . . . . . . . . . . . . . . . . . . . xix

1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Anthony J. Rothschild, M.D.

2 Schizophrenia and Schizoaffective Disorder . . 5

Jayendra K. Patel, M.D.
Kristina M. Deligiannidis, M.D.

TREATMENT GOALS . . . . . . . . . . . . . . . . . . . . . . . . 6
CLINICIAN-PATIENT RELATIONSHIP . . . . . . . . . . . . 7
ANTIPSYCHOTIC MEDICATIONS . . . . . . . . . . . . . . 8
TREATMENT OF SCHIZOPHRENIA . . . . . . . . . . . . . 20
TREATMENT OF SCHIZOAFFECTIVE DISORDER . . . 37
TREATMENT ADHERENCE . . . . . . . . . . . . . . . . . . . 39
KEY CLINICAL POINTS . . . . . . . . . . . . . . . . . . . . . 39
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
3 Mood and Anxiety Disorders . . . . . . . . . . . . 45
Kristina M. Deligiannidis, M.D.
Anthony J. Rothschild, M.D.

BIPOLAR DISORDER . . . . . . . . . . . . . . . . . . . . . . . 45
KEY CLINICAL POINTS: BIPOLAR DISORDER . . . . 53
PSYCHOTIC DEPRESSION . . . . . . . . . . . . . . . . . . . 54
KEY CLINICAL POINTS: PSYCHOTIC DEPRESSION . . 58
TREATMENT-RESISTANT DEPRESSION . . . . . . . . . . 59
KEY CLINICAL POINTS: TREATMENT-RESISTANT
DEPRESSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
NONPSYCHOTIC DEPRESSION . . . . . . . . . . . . . . . 61
KEY CLINICAL POINTS: NONPSYCHOTIC
DEPRESSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
OBSESSIVE-COMPULSIVE DISORDER . . . . . . . . . . 63
KEY CLINICAL POINTS: OBSESSIVE-COMPULSIVE
DISORDER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
GENERALIZED ANXIETY DISORDER. . . . . . . . . . . . 72
KEY CLINICAL POINTS: GENERALIZED ANXIETY
DISORDER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
POSTTRAUMATIC STRESS DISORDER . . . . . . . . . . 81
KEY CLINICAL POINTS: POSTTRAUMATIC STRESS
DISORDER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
SAFETY AND TOLERABILITY OF ANTIPSYCHOTICS
IN MOOD AND ANXIETY DISORDERS:
FUNDAMENTAL CONCEPTS . . . . . . . . . . . . . . . . . 90
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92
4 Personality Disorders . . . . . . . . . . . . . . . . . . 101
Kenneth R. Silk, M.D.
Michael D. Jibson, M.D., Ph.D.
HOW PSYCHOSIS IS VIEWED
IN PERSONALITY DISORDER . . . . . . . . . . . . . . . . 102
HISTORICAL CONSIDERATIONS. . . . . . . . . . . . . 103
MECHANISM OF ACTION . . . . . . . . . . . . . . . . . 104
INDICATIONS AND EFFICACY. . . . . . . . . . . . . . . 105
CLINICAL USE . . . . . . . . . . . . . . . . . . . . . . . . . . 106
GUIDELINES FOR SELECTION AND USE . . . . . . . 108
SIDE EFFECTS AND THEIR MANAGEMENT . . . . . 110
BORDERLINE PERSONALITY DISORDER . . . . . . . 110
SCHIZOTYPAL PERSONALITY DISORDER . . . . . . 116
OTHER PERSONALITY DISORDERS . . . . . . . . . . . 121
KEY CLINICAL POINTS . . . . . . . . . . . . . . . . . . . . 122
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123

5 Substance Abuse Disorders. . . . . . . . . . . . . 125

Gerardo Gonzalez, M.D.
Ruben Miozzo, M.D., M.P.H.
Douglas Ziedonis, M.D., M.P.H.
SUBSTANCE-RELATED PSYCHOMOTOR
AGITATION . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126
SUBSTANCE-ASSOCIATED
PSYCHOTIC SYMPTOMS AND DISORDERS. . . . . 133
CO-OCCURRING DISORDERS . . . . . . . . . . . . . . 136
SUBSTANCE USE DISORDERS. . . . . . . . . . . . . . . 141
KEY CLINICAL POINTS . . . . . . . . . . . . . . . . . . . . 142
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143
6 Use of Antipsychotics in Children and
Adolescents. . . . . . . . . . . . . . . . . . . . . . . . . . 145
Bruce Meltzer, M.D.

INDICATIONS AND EFFICACY. . . . . . . . . . . . . . . 146

SECOND-GENERATION ANTIPSYCHOTICS . . . . . 163
FIRST-GENERATION ANTIPSYCHOTICS . . . . . . . 172
ANTIPSYCHOTIC TREATMENT OF
PEDIATRIC PSYCHIATRIC DISORDERS . . . . . . . . 180
DISCONTINUING ANTIPSYCHOTIC TREATMENT . . 185
KEY CLINICAL POINTS . . . . . . . . . . . . . . . . . . . . 185
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . 186

7 Use of Antipsychotics in Geriatric Patients . . 191

Ellen M. Whyte, M.D.
Charles Madeira

GENERAL PRINCIPLES OF MEDICATION

MANAGEMENT . . . . . . . . . . . . . . . . . . . . . . . . . . 192
AGE-SPECIFIC ISSUES RELATED
TO SIDE EFFECTS . . . . . . . . . . . . . . . . . . . . . . . . 193
RISKS UNIQUE TO PATIENTS WITH DEMENTIA . . . 200
USE OF ANTIPSYCHOTIC MEDICATIONS
IN LONG-TERM-CARE FACILITIES . . . . . . . . . . . . 202
MEDICATION MANAGEMENT FOR PATIENTS
WITH PSYCHIATRIC AND NEUROPSYCHIATRIC
DISORDERS . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203
KEY CLINICAL POINTS . . . . . . . . . . . . . . . . . . . . 212
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . 213
8 Use of Antipsychotics in Medically Ill
Patients . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 215
Marcus W. Tjia, M.D.
David F. Gitlin, M.D.

MEDICAL CONSIDERATIONS IN THE USE OF

ANTIPSYCHOTICS . . . . . . . . . . . . . . . . . . . . . . . 216
GENERAL CONDITIONS . . . . . . . . . . . . . . . . . . . 218
MEDICAL DISORDERS . . . . . . . . . . . . . . . . . . . . 222
KEY CLINICAL POINTS . . . . . . . . . . . . . . . . . . . . 238
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . 238

Appendix 1
Names, Strengths, and Formulations of
First- and Second-Generation
Antipsychotics. . . . . . . . . . . . . . . . . . . . . . . . . . .241

Appendix 2
Pharmacokinetics of First- and Second-
Generation Antipsychotics . . . . . . . . . . . . . . . .249

Appendix 3
Dosing and Administration of First- and
Second-Generation Antipsychotics
in Schizophrenia . . . . . . . . . . . . . . . . . . . . . . . . .261

Appendix 4
Medical Workup When Initiating and
Continuing First- and Second-Generation
Antipsychotics. . . . . . . . . . . . . . . . . . . . . . . . . . .275

Appendix 5
Medical Workup When Initiating and
Continuing Clozapine . . . . . . . . . . . . . . . . . . . .279
Appendix 6
Use of First- and Second-Generation
Antipsychotics for Agitation Due to
Psychosis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .283

Appendix 7
Side Effects of Commonly Used
Antipsychotics. . . . . . . . . . . . . . . . . . . . . . . . . . .289

Appendix 8
Management of Treatment-Emergent
Side Effects of Antipsychotic Medications . . . .291

Appendix 9
Use of First- and Second-Generation
Antipsychotics in Pregnancy and Lactation . . .297

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .331
Contributors
Kristina M. Deligiannidis, M.D.
Director, Depression Specialty Clinic, and Assistant Professor of Psychiatry,
Department of Psychiatry, University of Massachusetts Medical School,
Worcester, Massachusetts

David F. Gitlin, M.D.

Assistant Professor of Psychiatry, Harvard Medical School; and Director,
Division of Medical Psychiatry, Brigham and Women’s Hospital, Boston,
Massachusetts

Gerardo Gonzalez, M.D.

Associate Professor, Department of Psychiatry, University of Massachusetts
Medical School, Worcester, Massachusetts

Michael D. Jibson, M.D., Ph.D.

Professor of Psychiatry and Director of Residency Education, University of
Michigan Health System, Ann Arbor, Michigan

Charles Madeira
University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Bruce Meltzer, M.D.

Assistant Professor of Pediatrics and Child Psychiatry, University of Massa-
chusetts Medical School, Worcester, Massachusetts; and Executive Medical
Director, UMASS/DMH Continuing Care Programs, Worcester and Westbor-
ough State Hospital, Westborough, Massachusetts

Ruben Miozzo, M.D., M.P.H.

Assistant Professor, Department of Psychiatry, University of Massachusetts
Medical School, Worcester, Massachusetts

xiii
xiv THE EVIDENCE-BASED GUIDE TO ANTIPSYCHOTIC MEDICATIONS

Jayendra K. Patel, M.D.

Director, Schizophrenia Research; Director, Bipolar Disorder Program, Cen-
ter for Psychopharmacologic Research and Treatment; and Associate Profes-
sor, Department of Psychiatry, University of Massachusetts Medical School,
Worcester, Massachusetts

Anthony J. Rothschild, M.D.

Irving S. and Betty Brudnick Endowed Chair and Professor of Psychiatry,
Department of Psychiatry, University of Massachusetts Medical School and
UMass Memorial Healthcare, Worcester, Massachusetts

Kenneth R. Silk, M.D.

Professor of Psychiatry, Department of Psychiatry, University of Michigan
Health System, Ann Arbor, Michigan

Marcus W. Tjia, M.D.

Instructor in Psychiatry, Harvard Medical School; and Assistant Director,
Division of Medical Psychiatry, Brigham and Women’s Hospital, Boston,
Massachusetts

Ellen M. Whyte, M.D.

Assistant Professor of Psychiatry and Physical Medicine and Rehabilitation,
University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Douglas Ziedonis, M.D., M.P.H.

Professor and Chair, Department of Psychiatry, University of Massachusetts
Medical School, Worcester, Massachusetts
Contributors xv

Disclosure of Competing Interests

The following contributors to this book have indicated a financial interest in or
other affiliation with a commercial supporter, a manufacturer of a commercial prod-
uct, a provider of a commercial service, a nongovernmental organization, and/or a
government agency, as listed below:
Gerardo Gonzalez, M.D.: Research support: Bristol-Myers Squibb, UCB;
Honoraria as speaker: Reckitt Benckiser
Michael D. Jibson, M.D., Ph.D.: Speaker’s bureau: AstraZeneca; “Up-to-
Date” author
Jayendra K. Patel, M.D.: Research support: Bristol-Myers Squibb, Founda-
tion for National Institutes of Health, Forest, Johnson & Johnson, National
Institute of Mental Health
Anthony J. Rothschild, M.D.: Grants/Research support: Cyberonics, National
Institute of Mental Health, Takeda, Wyeth; Consultant: Forest, GlaxoSmith-
Kline, Lilly, Pfizer; Royalties: Rothschild Scale for Antidepressant Tachy-
phylaxis (RSAT)™
Kenneth R. Silk, M.D.: Royalties: American Psychiatric Press, Cambridge
University Press
Ellen M. Whyte, M.D.: Grant funding: National Institute of Mental Health,
NICHD/NCMRR; Investigator-initiated grants: Forest, Lilly, Ortho-McNeil,
Pfizer
The following authors have no competing interests to report:
Kristina M. Deligiannidis, M.D.
David F. Gitlin, M.D.
Charles Madeira
Bruce Meltzer, M.D.
Marcus W. Tjia, M.D.
This page intentionally left blank
Acknowledgments

I have many people to thank for their encouragement, advice, and support in
preparing this book. My family has been patient and understanding of my
need to spend time on this project. Irving and Betty Brudnick were instru-
mental by their endowment of the Irving S. and Betty Brudnick Endowed
Chair at the University of Massachusetts Medical School, a position that al-
lowed me the time to focus on projects such as this evidence-based guide. I
am eternally grateful to Irving Brudnick’s wisdom and support, and I miss his
guidance greatly.
At American Psychiatric Publishing, Inc., Robert Hales, Editor-in-Chief;
John McDuffie, Editorial Director; and Greg Kuny, Managing Editor, Books,
deserve a great deal of credit for their unwavering confidence in me as an au-
thor and for their support throughout the development and production of this
evidence-based guide.
A special thank-you goes to Dr. Kristina Deligiannidis of the University of
Massachusetts Medical School for creating the informative tables in the Ap-
pendix of this book. My assistant Karen Lambert provided invaluable help in
the typing of the manuscript, figures, and tables. I am also appreciative of the
support and encouragement of colleagues and trainees at the University of
Massachusetts Medical School and UMass Memorial Healthcare. Finally, this
book could not have been written without the many patients and families with
whom I have had the privilege of working.

xvii
This page intentionally left blank
Disclaimer

Specific treatment regimens for a particular patient remain the responsibility

of the treating clinician, who has access to all of the patient’s relevant clini-
cal information, can make a complete assessment of the patient with the in-
formation in this textbook as appropriate, and can provide the most informed
medical advice. The information provided in this textbook is educational in
nature and for general use only and should not be seen as medical advice for
a specific patient or as the rendering of professional services. The latest
manufacturer’s package information for any medications or devices dis-
cussed in this book should be reviewed before prescribing for use. Informa-
tion provided may include a description of the uses of therapeutic and
biological products that have not been approved by the U.S. Food and Drug
Administration. Medical practice, research, and pharmacological advances
will occur, and, therefore, changes in the information and therapies in this
book are expected to occur.

xix
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