Neuropsychiatry 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 permission of the publisher (Springer-Verlag New York, Ine., 175 Fifth Avenue, New York, NY 10010, USA), exeept for brief exeerpts in conneetion with reviews or seholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use of general descriptive names, trade names, trademarks, ete., in this publication, even if the former are not especially identified, is not to be taken as a sign that such names, as understood by the Trade Marks and Merchandise Marks Act, may aeeordingly be used freely by anyone. While the advice and information in this book is believed to be true and accurate at the date of going to press, neither the authors nor the editors nor the publisher can aeeept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express of implied, with 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.