Table Of ContentNeuropsychiatry
and
Behavioral Pharmacology
c.
Thomas Gualtieri
N europsychiatry
and
Behavioral Pharmacology
Springer-Verlag
New York Berlin Heidelberg London
Paris Tokyo Hong Kong Barcelona
C. Thomas Gualtieri
Medical Director
at North Carolina Neuropsychiatry
Chapel Hili, NC 27516
and
at Rebound, Inc.
Hendersonville, TN 37077, USA
Gualtieri, C. Thomas
Neuropsyehiatry and behavioral pharmaeology I C. Thomas Gualtieri.
p. em.
IncIudes bibliographieal referenees.
ISBN-13:978-0-387-97314-2 e-ISBN-13:978-1-4613-9036-7
DOI: 10.1007/978-1-4613-9036-7
1. Neuropsyehiatry. 2. Psyehopharmaeology. 3. Brain-Wounds and
injuries-Complieations and sequelae. 4. Brain-Diseases
Complieations and sequelae. I. Title.
[DNLM: 1. Behavior-drug effeets. 2. Brain Injuries
eomplieations. 3. Brain Injuries-psyehology. 4. Organie Mental
Disorders-psyehology. 5. Psyehotropie Drugs-therapeutie use. WL
354 G912n]
RC343.Q35 1990
616.8-de20
DNLM/DLC 90-9805
Printed on aeid-free paper.
© 1991 Springer-Verlag New York, Inc.
All rights reserved. This work may not be translated or eopied in whole or in part without the written
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respeet to the material contained herein.
Text prepared on Xerox Ventura Publisher using author-supplied WordPerfect disks.
987654321
ISBN -13 :978-0-387-97314-2
Ta Anthony Powell, his brothers and sisters, 199Q
Contents
Introduction............................................................................................ Xl
1. The Neuropsychiatric Sequelae of Traumatic Brain Injury .......... 1
The Neurobehavioral Sequelae of Traumatic Brain Injury • The
Prediction of Outcome • The Trajectory of Recovery' Evaluation of
the TBI Patient
2. Delayed Neurobehavioral Sequelae of Traumatic
Brain Injury ................................................................................... 26
Affective Disorders • Delayed Amnesia • Posttraumatic Epilepsy •
Psychosis • Dementia
3. The Psychopharmacology ofTraumatic Brain Injury ................... 37
Principles of Treatment· Psychostimulants • Amantadine • Other
Dopamine Agonists • Antidepressants • Lithium' Neuroleptics • The
Psychotropic Anticonvulsants • Benzodiazepines • Buspirone • Beta
Adrenergic Blockers' Alpha Agonists' Calcium Channel Blockers
• Opiates • Other Neuropeptides • Cholinergic Drugs' Nootropes'
Cranial Electrostimulation (CES) • Examining the Patient on
Psychoactive Medication
4. Inadvertent Drug Effects ................ ............................ .................. 89
Licit Drugs • Illicit Drugs • Drugs Prescribed for Medical Reasons'
H2 Receptor Antagonists • Sympathomimetics • Antispasticity Drugs
viii Contents
5. Epilepsy ....................................................................................... 102
Neuropsychiatric Conditions in Epileptic Patients • Psychiatric
Conditions That May Be Related to Epilepsy • Neuropsychological
and Behavioral Effects of Anticonvulsant Drugs • Psychotropic
Drugs as Convulsants and as Anticonvulsants
6. Neuropsychiatrie Oisorders in Mentally Retarded People ......... 124
Traditional Psychiatric Disorders • Behavioral Disorders • Pathobe-
havioral Mental Retardation Syndrome· Disorders of Serotonin
Regulation
7. Self-Injurious Behavior ............................................................... 159
The Pharmacotherapy of SIB • Testing the Dl Model· The
Differential Diagnosis of SIB
8. Behavior in the Cornelia Oe Lange Syndrome ........................... 173
The CDLS Survey • Contrasting Data • Behavior in the Cornelia de
Lange Syndrome
9. Autism ......................................................................................... 187
Wh at Is Autism?· The Psychopharmacology of Autism •
Psychopharmacology for Autistic People· Epilepsy· Self-
Injurious Behavior· Aggression· Obsessive-Compulsive Behavior
• Tourette's Syndrome· Abulia • Affective Disorders • Anxiety,
Agitation, and Panie· Psyehosis and Sehizophrenia· Hyperaetive or
Disorganized Behavior • The Kluver-Bucy Syndrome· Megavitamins
10. Tardive Oyskinesia ..................................................................... 209
The Prevalence of Serious Neuroleptic Side Effects • Risk Faetors
for Tardive Dyskinesia • Biological Mechanisms • Diagnosis •
Treatment· The Course of the Disorder • Malignant TD • Behavioral
and Cognitive Manifestations of Tardive Dyskinesia • Neuroleptic
Nonresponders • Alternatives to Neuroleptic Treatment· Tardive
Dyskinesia Policy and Recommendations • TMS: A System for
Prevention and Control • The Development of TMS
11. Three Neuropsychiatrie Conditions of Childhood ....................... 235
Childhood Hyperactivity • The Kleine-Levin Syndrome· Rheumatic
Psyehosis
Contents ix
12. Behavioral Psychopharmacology ...... .......... ................ ................. 255
Therapeutic Trials Are Hypothesis Testing Theoretical Models Run
0
in Parallel Behavior Is a Measurable Thing There Is a Personal
0 0
Economy to Consider And a Wider Economy Structure
0 0 0
Epilepsy Is First In Fever of Unknown Origin, Stop All Drugs
0 0
Overt Toxicity Is Not a Bad Thing Long-Term Drugs Require
0
Long-Term Evaluation Doses are Empiricalo "Yes-No" Drugs oYou
0
Do Not Know Until You Try Monitoring Is No Substitute for
0
Intelligence
Afterword .............................................................................................. 268
Appendices ........................................................................................... 271
References ............................................................................................ 277
Index ..................................................................................................... 345
Introduction
Neuropsychiatry is applied neuroscience. The brain, not behavior, is its point of
departure. In this, it is distanced from the concerns of traditional psychiatry, which
is built around the primacy of behavior. The neuropsychiatrist is concerned with
brain, and behavior is derivative.
Neuropsychiatry has been defined, in the past, with a narrow view of its proper
domain: disorders that are clearly related to alesion, like stroke; orto adegenerative
disease, like Alzheimer's or Parkinson's; or to a systemic condition that affects
brain, like Lupus, for example. Our interest, and the concern of this book, is with
a different class of neuropsychiatric conditions, and they are hardly ever dealt with
in the literature. They are the behavioral syndromes that arise as a result of
congenital or acquired brain injuries.
So, this is what we are about: the neuropsychiatric effect of traumatic brain
injury, the behavioral syndromes associated with mental retardation, and a few of
the development disabilities of childhood. The subject of our concern is, therefore,
unique. It is different from the usual concern of neuropsychiatrists, behavioral
neurologists, and neuropsychologists. There is also a different approach to the
subject.
The concern is not with lesions but with prototypes, prototypes of mechanisms
that govern brain, and disorders of brain. It is with the clinical meaning of specific
neurophysiological processes, like kindling, reciprocal inhibition and activation,
long-term potentiation, and time-dependent sensitization; of specific neurophar
macologic processes; of the laws that govern the expression of human traits,
collectively known by the name of behavioral genetics; and of the interaction
between these elements and the personal ecology of the neuropsychiatric patient.
The paradigms and mechanisms around these elements are only imperfectly
understood. But they are, quite clearly, the presage ofhow we shall, someday, come
to understandthe brain and its disorders.
Since neuropsychiatry is an applied science, it bOITOWS models and paradigms
from all of the preclinical neurosciences. Since it is a clinical sci'ence, it employs
these models in the service of diagnosis and treatment. The art is in deciding which
model is most appropriate to a give clinical circumstance; there is always a wide
range of theoretical and empirical structures to choose among. This book is about
a few clinical conditions where cogent models are at hand, and seem to be germane
to diagnosis and treatment.
Introduction
Xli
The book is oriented towards developmelltal neuropsychiatry: that is, the con
genital and the acquired disorders of relatively young people. It is concemed with
relatively static conditions; the neurodegenerative disorders, that are usually the
mainstay of neuropsychiatry, are not dealt with here.
Although the patients we shall discuss have static disorders, some degree of
functional recovery may always be expected. Treatment is designed not to slow the
course of degeneration, but to enhance natural, compensatory healing processes.
The clinical problems we shall address are the severe behavior disorders of
children, of retarded people, of people with epilepsy and of victims of traumatic
brain injury. They are clinical problems for which effective treatment may be
expected to bring years of useful and productive living.
Treatment is the focus. There is clearly a need for a manual of practical
therapeutics in this field. There is no current book oriented to the requirements of
professionals in developmental neuropsychiatry, that presents practicaladvice
within a theoretical framework.Treatment is also a window. It is a way to test the
validity of theoretical models in the real world. It is, after all, a very good way to
discover whether a neuroscientific paradigm has practical value. It is also a good
place to generate ideas. In our opinion, one should never consider a field of clinical
endeavor to be entirely derivative of basic science. There is an integrity to the
applied sciences that is co-equal with the "purity" of the basic sciences.
The treatment with which we are most directly concemed is psychopharmacol
ogy, but we prefer the term behavioral pharmacology. That is because the
therapeutic approach to our unconventional patients is only rarely syndromic, in
the sense of the Kraepelinian DSM-3. Approaches to treatment that are symptom
matic, functional or hypothetical, as we shall describe, deserve to occupy an equal
rank with approaches that are purely syndromic, in terms of psychiatric orthodoxy.
Treatments are oriented to changes in specific target behaviors, to improvement in
specific cognitive or regulatory functions, or to testing specific hypotheses con
ceming the etiopathogenesis of a dis order. It is the special method one uses to deal
with psychiatric problems in patients who cannot be classified by psychiatrists. It
is entirely empirieal, and it places more reliance on treatment response over time
than on front-end diagnostic exercises.
This book is about a diverse group of patients-patients with whom we are very
familiar, clinical problems that have been t~e focus of our research and teaching.
The organization of the book is not comprehensive, however, since it is built around
a few conditions with which we have had a great deal of experience. The interests
of our research group have always been around the psychopharmacology of
unusual populations. Events have conspired to lend a certain unity to our work, a
framework that is captured in the title of the book, if not in its subsequent
construction.
But the problems are new and interesting, and since they have not been, as a rule,
the subject of a great deal of research by other clinical scientists, it is possible that
our opinion will appear novel. Not as signal insights or as fundamental truths,
perhaps, but, at least, as new perspectives.
CHAPTER 1
The Neuropsychiatrie Sequelae of
Traumatic Brain Injury
The number of people with disabilities from serious brain injury is growing fast;
they are one of the largest populations of neuropsychiatric patients in the United
States. There are two reasons for this extraordinary phenomenon.
The first reason is that patients who have sustained severe head injuries, for
example in motor vehicle accidents, are now more likely to survive, compared even
to ten years ago. Med-Evac technology and intensive neurosurgical care are better.
The statistic, often cited, is that 10 years aga 90% of closed head injury (CHI)
victims died. Today, 90% survive. Each year there are about 500,000 new brain
injury victims in the United States; each year, 75,000 or 100,000 victims of
traumatie brain injury (TBI) are left with significant disability (Kraus, 1987).
As we have learned more about the neurobehavioral consequences of severe
head injury, we have also learned to appreciate the milder but similar consequences
of mild head injury. People who have survived severe head injuries are around to
tell what it is like, and they tell us what the victims of mild head injuries have been
saying all along. This is a difference in degree, obviously, but not a difference in
kind. A few years ago, victims of "postconcussion syndrome" were thought to be
hypochondriacs, or "compensation neurotics." Now we appreciate that their
problems are real. The second reason why the number ofTBI patients is increasing
is that we have learned what the neuropsychiatric consequences of "mild" brain
injury really are.
The problems of mild head injury victims have been documented in
epidemiologie studies (Colohan et al., 1986; Rimel et al., 1981; Rutherford et al.,
1979; Gronwall and Wrightson, 1974; Alves et al. , 1986; Barth et al., 1983).
Research with laboratory animals has confirmed that comparatively mild injuries
can have lasting neuropathic sequelae, that neural tissue can be seriously damaged,
or even destroyed, by comparatively mild trauma to the head (e.g., lane et al. , 1982).
Until recently, the only professionals with any interest in TBI were the clinical
neuropsychologists, and until recently they were a small, unimportant group of
specialists within psychology. Their clinical work was largely confined to the
Veterans Hospitals, where they worked with the victims of battlefield injuries.
There would be a spate of new head injury research after every war; for example,
the work of Kurt Goldstein after World War I, and that of Alexander Luria and
William Lishman after World War 11.
