Table Of ContentBIOMEDICAL
PSYCHIATRIC
THERAPEUTICS
Edited by
John L. Sullivan, M.D.
Professor of Psychiatry, Georgetown University, George
Washington University and Duke University Schools of
Medicine; Psychiatrist-in-Chief, Veterans Administration
Medical Center, Washington, D.C.; Former Deputy
Director of Medical Research for the Veterans
Administration
Paula DeRemer Sullivan, Ph.D.
Clinical Psychologist, Suburban Psychiatric Associates,
Bethesda, Maryland
With 27 contributing authors
Foreword by Morris A. Lipton, Ph.D., M.D.
Introduction by John M. Davis, M.D.
BUTTERWORTH PUBLISHERS
Boston · London
Sydney · Wellington · Durban · Toronto
Copyright © 1984 by Butterworth Publishers
All rights reserved.
No part of this publication may be reproduced, stored in a
retrieval system, or transmitted, in any form or by any means,
electronic, mechanical, photocopying, recording, or otherwise,
without the prior written permission of the publisher.
Every effort has been made to ensure that the drug dosage
schedules within this text are accurate and conform to standards
accepted at time of publication. However, as treatment
recommendations vary in light of continuing research and clinical
experience, the reader is advised to verify drug dosage schedules
herein with information found on product information sheets.
This is especially true in cases of new or infrequently used drugs.
Library of Congress Cataloging in Publication Data
Main entry under title:
Biomedicai psychiatric therapeutics.
Bibliography: p.
Includes index.
1. Psychopharmacology. 2. Mental illness—
Physiological aspects. I. Sullivan, John L. (John
Lawrence), 1943- . II. Sullivan, Paula DeRemer.
[DNLM: 1. Mental disorders—Therapy. WM 400 B6155]
RC483.B54 1984 616.8918 83-26328
ISBN 0-409-95151-X
Butterworth Publishers
80 Montvale Avenue
Stoneham, MA 02180
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Printed in the United States of America
To our families
FOREWORD
Over the past 30 years, biological psychiatry has moved ahead of psychoanal
ysis as the dominant force in psychiatric training, research, and treatment.
The brain is no longer a "black box" impervious to investigation except by its
output as seen in the behavior of patients, especially in their transactions with
therapists. It is now recognized as the complex organ of the mind which inter
acts constantly with the rest of the body, responding to changes in the inter
nal milieu and, through its output, regulating most bodily functions. It also
responds to the external milieu and is altered by it. With modern technology,
it is a researchable organ which is attracting the attention and efforts of our
best young people.
These remarkable changes started with two simultaneous develop
ments. The first was the empirical discovery of drugs which in small doses
could alter perception, mood, thinking, and behavior. Since drugs are chemi
cals which cannot influence metapsychological constructs but instead must
act on chemical systems within the brain, the nature of the changes they pro
duce in the brain has become the subject of intense investigation. At about the
same time, the chemical theory of neurotransmission superseded electrical
theories and it became evident that neuronal cells communicate with each
other across synapses by means of very specific chemical neurotransmitters
and receptors for them. Psychotropic drugs, it was soon found, influence the
production, storage, and release of neurotransmitters in presynaptic neurons
and their reception by postsynaptic neurons. Thus, a very profitable partner
ship between basic and clinical neurobiology was initiated and continues vig
orously to this day. In recent years, the number of identified neurotransmit
ters, including the peptides, has increased to more than 20. The nature of
receptors is being clarified. Endogenous ligands such as the endorphins are
being discovered for several of the receptors. An intellectual fusion between
neurobiology and molecular biology and genetics is also taking place.
The shift in perspective toward biological mechanisms has had pro
found consequences on psychiatric training and practice. Modern programs
for the training of psychiatrists do not neglect the subjective, psychological,
and social factors that influence health and illness, but to them are added
training in basic and clinical neurobiology. The depth and breadth of informa
tion which the young psychiatrist must master is now substantially greater
than was required in the past. A second consequence is that psychiatry has
moved closer to the mainstream of medical thinking and practice. Greater
rigor in diagnosis, greater specificity in the choice of treatment, and greater
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X BIOMEDICAL PSYCHIATRIC THERAPEUTICS
objectivity in the measurement of change are now demanded. Instruments
have been developed for these purposes and are under constant refinement.
Drugs are the primary therapeutic agents in biological psychiatry. For
many reasons, their use is far from simple, and that fact is made clear
throughout this book. Drugs are not "magic bullets," absolutely specific for a
given disease and devoid of side effects. Illnesses such as anxiety, depression,
and schizophrenia are probably syndromes, each of which has several biolog
ical etiologies. The various members of a "labeled" class of drugs, such as, for
example, the antidepressants, are not equally effective in all patients. Proba
bly this is partly attributable to the etiological heterogeneity of the syndromes
being treated. Certainly it is due to the genetic heterogeneity of human
beings, which influences the rate at which drugs may be absorbed and metab
olized. Thus, with a given dose, individual patients achieve different blood
levels and have varying pharmacokinetic patterns, and these can be mea
sured by appropriate laboratory tests. The chronic effects of drugs often differ
from their acute effects. Drugs interact with each other, a matter of consider
able importance to the patient receiving drugs for a medical illness along with
psychotropic agents. Drugs sometimes have surprising effects. The tricyclic
antidepressants and monoamine oxidase inhibitors so commonly identified as
antidepressants are also effective in the treatment of panic attacks. Why this is
so is not yet clearly understood.
The information explosion in biological psychiatry has been so great that
a single individual can no longer write a text. Moreover, no student, scholar,
or practitioner can possibly keep up with the wealth of material that appears
daily in refereed journals, monographs, reviews, and specialty texts. Practi
tioners especially, who must make daily diagnostic and therapeutic decisions,
lack the time to reflect at leisure while controversies are being resolved and
must depend heavily upon the information and critical judgments offered to
them by the authors of texts. The editors of this volume have chosen their
authors wisely. Not only are they experienced clinicians and clinical research
ers, they are also teachers who present their material lucidly. The result is an
up-to-date, "state-of-the-art" text with a bonus from Dr. Wyatt, one of our
most distinguished investigators in biological psychiatry, who attempts to
predict the future. This is always chancy, but Dr. Wyatt is undoubtedly cor
rect in believing that the syndrome of schizophrenia will be broken down into
subgroups that can then be understood and treated more effectively. He an
ticipates that the new technologies of positron emission tomography, nuclear
magnetic resonance, and electrophysiological mapping of the cortex will yield
new insights. His forecasts will probably prove correct, but part of the adven
ture of research is its unpredictability. Newer discoveries about the roles of
the peptides and neurotransmitters, about genetic markers and genetic en
gineering, may surprise us as much a generation from now as did the psycho-
tropic drugs when they emerged in the 1950s.
Every text is a compromise between the requirements of the publishers,
the wishes of the authors, and the value system of the editor. What topics
FOREWORD xi
shall be chosen and what will be omitted? To what extent should the basic
science substrates of the clinical information be expounded? How shall areas
of controversy be discussed? This book is an excellent compromise in a format
which can readily be revised in later editions. Not the least of its virtues are
bibliographies which offer both original articles and up-to-date reviews for
those who wish greater depth on pertinent topics.
A potential concern in a book such as this has been alluded to by Leon
Eisenberg, who warned: "Biological psychiatry threatens to become so my
opic in its clinical vision that it threatens to substitute mindless psychiatry for
the brainless psychiatry of the past. It is disregarding its social and psycholog
ical context" (Eisenberg, L. The subjective in medicine. Perspect Biol Med
27:24, 1983). Comprehensive medical care involves human transactions for
which drugs will never be a total substitute, and any text which focuses on
the biomedicai aspects of psychiatry risks neglecting that fact. Fortunately, no
one knows this better than the editors and authors of this book. In addressing
major psychosocial considerations relevant to biomedically oriented treat
ment, they underscore the importance of a balanced therapeutic perspective
in the comprehensive care of the patient.
Morris A. Lipton, Ph.D., M.D.
PREFACE
The last several decades have witnessed psychiatry's evolution as a scientif
ically based and practical medical specialty, with attendant differentiation
along subspecialty lines in order to accommodate the burgeoning depth and
diversity of the discipline. One of the most rapidly evolving of these sub-
specialty areas, biomedicai psychiatry, deals with the biological basis of
mental illness, biological diagnostic and treatment techniques, and special
problems associated with the biomedicai treatment of psychiatric patients
with concurrent nonpsychiatric medical illness.
Most of the significant developments in biomedicai psychiatry have im
pacted on the management of psychiatric patients in a variety of clinical set
tings. Therefore, we have attempted to develop a book that can serve as a
general reference text on biomedicai psychiatric therapeutics for students,
house staff, and practitioners engaged in the care of psychiatric patients or
patients with a psychiatric component to their illness.
The text is divided into three parts: (1) general treatment approaches, (2)
special topics, and (3) future directions. The first part primarily addresses
basic principles of biomedicai psychiatric therapeutics, and the second part
discusses special areas of major clinical importance where biomedicai psychi
atry interfaces with other medical specialties or psychiatric subspecialties. Al
though a number of other special areas such as the chemical dependencies,
pediatrie psychopharmacology, and consultation-liaison psychiatry, to name
just a few, could also have been selected for this part, we have limited our
selves to several areas that have seen substantive changes in recent years or
that are fundamentally important to the clinical practice of biomedicai psychi
atric therapeutics. The third part discusses advances in biological exploration
of psychiatric disorders that are expected to have a significant impact on bio-
medical psychiatric therapeutics in the near future.
In preparing this text, we have been constantly mindful of what is, per
haps, the most significant advance for American psychiatry in recent years:
the realization of the increasingly scientific, and integrated, nature of the dis
cipline. This achievement is reflected in the virtual disappearance of a philo
sophic orientation for psychiatry based upon theory and dogma alone,
without due regard for observation and experience, as well as erosion of a
strict dichotomous approach to the biological and psychosocial aspects of the
discipline. Consonant with this evolutionary advance, we are hopeful that
our readers appreciate our focus on an important area of psychiatry that,
XIII
xiv BIOMÉDICAL PSYCHIATRIC THERAPEUTICS
under appropriate circumstances, can contribute meaningfully to the com
prehensive care of the patient.
The editors and contributors of this volume are indebted to the support,
encouragement, and inspiration of a number of our colleagues, residents, and
students in the preparation of the manuscript, including Ms. Pearl Anderson;
Herbert Baganz, M.D.; SamBarondes, M.D.; Hollis Boren, M.D.; Keith Brodie,
M.D.; William Bunney, M.D.; Ewald Busse, M.D.; Mr. William Carey; Bernard
Carroll, M.D., Ph.D.; James Collins, M.D.; Don Custis, M.D.; Ms. Annie Dunn;
Jack E wait, M.D.; James Finkelstein, M.D.; EarlX. Freed, Ph.D.; Robert Friedel,
M.D.; Mr. Al Gavazzi; RichardGreene, M.D., Ph.D.; George Higgins, M.D.; Jeff
Houpt, M.D.; Lewis Judd, M.D.; Douglass Kay, M.D.; Kenneth Keller, Ph.D.;
Alex Kelly, M.D.; John Kurtzke, M.D.; C. Raymond Lake, M.D., Ph.D.; Robert
Lindeman, M.D.; Markku Linnoila, M.D., Ph.D.; John Lipkin, M.D.; Arnold
Mandell, M.D.; Victor McKusick, M.D.; Dennis Murphy, M.D.; Barbara
Palmeri, M.D.; Douglas Price, M.D.; Charles Rackley, M.D.; Louis Rittelmeyer,
M.D.; Allan Schwartzberg, M.D.; David Segal, Ph.D.; Ms. Cynthia Smith;
Vincent Tomasino, M.D.; Philip Tumulty, M.D.; Jerry Wiener, M.D.; William
Wilson, M.D.; and James Wyngaarden, M.D.
Finally, we thank Butterworth Publishers and our editors Mr. Arthur
Evans, Ms. Nancy Megley, Ms. Karen Myer, Ms. Elizabeth O'Neill, and Ms.
Patricia Sheehan for their patience and support in this venture.
J. L. S.
P. D. S.
CONTRIBUTING AUTHORS
Jesse O. Cavenar, Jr., M.D. Jonathan Davidson, M.D.
Professor of Psychiatry, Duke Associate Professor of Psychiatry,
University School of Medicine; Duke University School of
Psychiatrist-in-Chief, VA Medical Medicine; Attending Psychiatrist,
Center, Durham, North Carolina VA Medical Center, Durham,
North Carolina
Mary G. Cavenar, R.N., M.S.N.
Johnston Scholar, University of
John M. Davis, M.D.
North Carolina, Chapel Hill,
Gilman Professor of Psychiatry,
North Carolina
University of Illinois College of
Medicine; Director of Research,
C. Edward Coffey, M.D.
Illinois State Psychiatric Institute,
Assistant Professor of Psychiatry
Chicago, Illinois
and Medicine (Neurology), Duke
University School of Medicine;
Chief, Neuropsychiatrie Imaging Lynn E. DeLisi, M.D.
Program, Duke University Medical Staff Psychiatrist, Laboratory of
Center, Durham, North Carolina Psychology and Psychopathology,
National Institute of Mental
Joseph Cools, M.D. Health, Bethesda, Maryland
Clinical Associate in Psychiatry,
Duke University School of
William E. Fann, M.D.
Medicine; Chief, Inpatient
Professor of Psychiatry and
Psychiatry Division, Duke
Associate Professor of
University Medical Center,
Pharmacology, Baylor College of
Durham, North Carolina
Medicine; Psychiatrist-in-Chief,
VA Medical Center, Houston,
Tim Covington, Pharm.D.
Texas
Associate Professor of Clinical
Pharmacy, West Virginia
University School of Medicine; D. Ted George, M.D.
Coordinator of Clinical Pharmacy, Clinical Associate, Laboratory of
West Virginia University Clinical Science, National Institute
Medical Center, Morgantown, of Mental Health, Bethesda,
West Virginia Maryland
xv
xvi BIOMEDICAL PSYCHIATRIC THERAPEUTICS
Richard L. Goldberg, M.D. E. Wayne Massey, M.D.
Assistant Professor of Psychiatry, Associate Professor of Medicine
Georgetown University School of (Neurology), Duke University
Medicine; Director of Residency School of Medicine; Attending
Training, Department of Neurologist, Duke University
Psychiatry, Georgetown University Medical Center, Durham, North
Medical Center, Washington, D.C. Carolina
David M. Goldstein, M.D.
Assistant Professor of Psychiatry, Wesley M. Pitts, M.D.
Georgetown University School of Assistant Professor of Psychiatry,
Medicine; Chief, Adult Outpatient Baylor College of Medicine;
Division, Department of Attending Psychiatrist, VA
Psychiatry, Georgetown University Medical Center, Houston, Texas
Medical Center, Washington, D.C.
Martha M. Letterie, M.D.
Manuel Rodriguez-Garcia, M.D.
Instructor in Psychiatry,
Assistant Professor of Psychiatry,
Georgetown University School
Baylor College of Medicine;
of Medicine; Attending
Attending Psychiatrist, VA
Psychiatrist, VA Medical Center,
Medical Center, Houston, Texas
Washington, D.C.
Morris A. Lipton, Ph.D., M. D.
Donald R. Ross, M.D.
Sarah Graham Kenan Professor of
Attending Psychiatrist, Sheppard
Psychiatry, University of North
and Enoch Pratt Hospital,
Carolina School of Medicine;
Baltimore, Maryland
Director, Biological Sciences
Research Center of the Child
Development Research Institute,
John L. Sullivan, M.D.
Chapel Hill, North Carolina
Professor of Psychiatry,
Steve Mahorney, M.D. Georgetown University, George
Associate in Psychiatry, Duke Washington University and Duke
University School of Medicine; University Schools of Medicine;
Attending Psychiatrist, Psychiatrist-in-Chief, VA Medical
VA Medical Center, Durham, Center, Washington, D.C; Former
North Carolina Deputy Director of Medical
Research for the Veterans
Allan A. Maltbie, M.D. Administration
Associate Professor of Psychiatry,
Duke University School of
Medicine; Chief, Consultation- Paula DeRemer Sullivan, Ph.D.
Liaison Division, Duke University Clinical Psychologist, Suburban
Medical Center, Durham, North Psychiatric Associates, Bethesda,
Carolina Maryland
