Thursday, 09.04.2020

Thomas A. Ban
Neuropsychopharmacology in Historical Perspective.

Education in the field in the Post-Psychopharmacology Era

Collated 20

Thomas A. Ban: Schizophrenia in the Early 1970s

 

         In the early 1970s two monographs of Thomas Ban on schizophrenia were published in Springfield, IL, by Charles C. Thomas in their American Lecture Series. In one, “Schizophrenia A Psychopharmacological Approach,” the changes affected in patients in a broad sense by the introduction of chlorpromazine and other neuroleptic drugs that followed are described; in the other, “Recent Advances in the Biology of Schizophrenia,” findings in research, with possible relevance to the biological underpinning of schizophrenia, are discussed

 

Thomas A. Ban:  Schizophrenia A Psychopharmacological Approach.

Springfield: Charles C. Thomas; 1972. (134 pages)

Reviewed by Thomas A. Ban

 

INFORMATION ON CONTENTS: This monograph is divided into five chapters: Introduction (Chapter 1), Drugs (Chapter 2), Patients (Chapter 3), Schizophrenias (Chapter 4) and Concluding Remarks (Chapter 5). They are preceded by a Preface and Acknowledgments followed by a Bibliography and two Indexes (Authors and Subjects).

         In Chapter 1 (Introduction), a brief, enthusiastic account is given for the introduction of chlorpromazine, the first neuroleptic in the treatment of schizophrenia around the world, from 1952 to 1955. In Chapter 2 (Drugs), the neuroleptics, introduced in the treatment of schizophrenia during the 18 subsequent years and their clinical effects are discussed. During these years the number of neuroleptics rapidly grew and by 1970 there were more than 20 neuroleptics in clinical use, with more or less equal overall therapeutic efficacy but without any clearly defined differential therapeutic indications.

         In Chapter 3 (Patients), the emphasis shifts from drugs to the effect of neuroleptics on Patients. Thus, information is presented on the effects of neuroleptic treatment on psychiatric hospitalization (population changes, duration of hospital stay, prevention of hospitalization) and on the behavior of patients in hospital; the effects of neuroleptics are compared to other available treatments (psychotherapies, physical therapies) for schizophrenia; and the changes affected by neuroleptics on the different psychiatric syndromes and psychopathological symptoms encountered in schizophrenic patients are discussed. A special section is dedicated to the characterization of schizophrenic patients in the community, the primary site of treatment after the introduction of neuroleptics.

         Finally, in Chapter 4 (Schizophrenias), the effects of neuroleptics on the schizophrenias are examined. In view of the pharmacological heterogeneity of responsiveness and the recognition that a patient refractory to treatment with one drug may respond to another, the possibility is raised of using pharmacological responsiveness for classifying patients. However, attempts for grouping patients in a clinically meaningful way on the basis of their pharmacological responsiveness have invariably failed. The same applies to the testing of biochemical hypotheses of schizophrenia which emerged during the 1960s and ’70s, such as anomalies of tryptophan metabolism, phenylalanine metabolism and transmethylation.

         The monograph concludes with the sobering statement that in spite of all the changes which have been encountered during the two decades after the introduction of chlorpromazine, schizophrenia in all civilized countries has remained a major public health problem; neuroleptics have helped but did not cure schizophrenic patients. Yet, the introduction of neuroleptics brought about a new way of thinking about schizophrenia that has generated testable biochemical hypotheses about the pathomechanism of the illness.

AUTHOR’S COMMENTS: This monograph is an expansion of my Hoffman-LaRoche Lecture at the Clarke Institute of Psychiatry, presented on January 15, 1971. It is also available in Japanese in Hayime Kazamatsuri’s translation.

 

Thomas A. Ban: Recent Advances in the Biology of Schizophrenia

Springfield: Charles C. Thomas; 1973. (119 pages)

Reviewed by Thomas A. Ban

INFORMATION ON CONTENTS: This monograph is divided into two parts: (Part One: Etiology and Part Two: Treatment) and 11 chapters: 1. Descriptive Classifications (Chapter 1), Conditional Reflex Correlates (Chapter 2), Neurophysiological Findings (Chapter 3), Biochemical Hypotheses (Chapter 4), Genetic Factors (Chapter 5), Present Status (Chapter 6), Pharmacotherapy with Neuroleptics  (Chapter 7), Prediction of Neuroleptic Effects (Chapter 8), Neuroleptics Versus Other Treatments (Chapter 9), Other Pharmacological Treatments (Chapter 10) and Present Status (Chapter 11).  Chapter 1 is preceded by a Preface and Acknowledgements and Chapter 11 is followed by Concluding Remarks, Bibliography and two Indexes (Authors and Subjects).

         In Chapter 1 (Descriptive Classifications), the controversy of the 1950s is addressed, namely whether the different forms of schizophrenia are progressive stages of one generalized disorder of the brain, as perceived by Klaus Conrad, or distinct, localized disorders of the brain, affecting one or more neurological system simultaneously, as perceived by Karl Kleist and Karl Leonhard.

         In Chapter 2 (Conditional Reflex Correlates), findings with conditioning test batteries in the 1960s are presented. It was noted that in 1962 Christian Astrup described the differential conditional reflex profiles of Carl Schneider’s three different forms of “acute schizophrenia” and Karl Leonhard’s 18 different forms/sub-forms of “chronic schizophrenia.”

         In Chapter 3 (Neurophysiological Findings), findings with surface electroencephalography (EEG) and averaged evoked potentials (AEP) are discussed. It was noted that no “exclusive EEG signs” of schizophrenia could be identified, but there was a relative excess of fast activity (EEG) and a greater variability in auditory evoked potentials (AEP) in schizophrenic patients than in normal subjects.  

         In Chapter 4 (Biochemical Hypotheses), numerous biochemical theories and speculations about the “cause” of schizophrenia are reviewed. They include: (1) normal products of phenylalanine metabolism, such as norepinephrine (NE) and dopamine (DA); (2) abnormal  products of phenylalanine metabolism, such as 3, 4-dimethoyphenylethylamine (DMPEA), adrenochrome and adrenolutin; (3)  psychotoxic dimethylated products of tryptophan metabolism, such as bufotenin and dimethyltryptamine; (4) transmethylation, i.e., the metabolic process itself; (5) nicotinamide adenine dinucleotide deficiency; and (6)  a plasma protein factor that interferes with the conversion of glucose into pyruvic acid (in vitro).  While none of these hypotheses were borne out by evidence, supportive of the role of DA in the pathogenesis of schizophrenia or at in the pathogenesis of some of the symptoms or syndromes of schizophrenia are findings which indicate that all neuroleptics with demonstrated therapeutic efficacy in the treatment of schizophrenia antagonize some of the central effects of DA.

         In Chapter 5 (Genetic Factors), the role of heredity in schizophrenia is examined. Findings in traditional twin studies, in studies in adopted away children of schizophrenic parents and in biochemical genetic investigations are reviewed. It was noted that in Pollin’s biochemical genetic investigation, urinary excretion levels of catecholamines were higher in both members of monozygotic twins discordant for schizophrenia than in normal subjects, whereas 17-OH steroid levels were higher only in the schizophrenic members of the pairs.

         In Chapter 6 (Present Status), Part One concludes as follows: “There is sufficient evidence to believe that schizophrenia is a genetic disease, although neither the nature of the genetic disturbance, nor the mode of transmission has been demonstrated to date. Similarly, there is sufficient evidence to believe that there are biochemical disturbances in schizophrenia, but whether they are the causes or the effects of the psychopathological manifestations is not known.”   

         In the remaining five chapters the focus in the monograph shifts from “etiology” to “treatment.”

         In Chapter 7 (Pharmacotherapy with Neuroleptics), the status of pharmacotherapy in schizophrenia with neuroleptics in the early 1970s is reviewed; findings related to neuroleptic dose requirements in the treatment of schizophrenia are presented; and information on neuroleptic dependence, toxicity and teratogenicity is discussed. 

         In Chapter 8 (Predictors of Neuroleptic Effects), possible predictors of treatment outcome with neuroleptics are examined, without success of identifying any. It was noted that early relapse after neuroleptic withdrawal might be predicted by the absence of a startle response.

         In Chapter 9 (Neuroleptics Versus Other Treatments), findings of efficacy studies in the treatment of schizophrenia in which neuroleptics are compared with other non-pharmacological treatments are reviewed. It is shown that neuroleptics compare favorably in the treatment of schizophrenia to milieu therapy, psychotherapy, insulin coma and electroshock.

         In Chapter 10 (Other Pharmacological Treatments), findings in the Canadian Mental Health Association Collaborative Studies on nicotinic acid in the treatment of schizophrenia are reviewed. It is shown that treatment with nicotinic acid in megadoses has no therapeutic effect in schizophrenia. 

         In Chapter 11 (Present Status), Part Two (Treatment) concludes: “In the foregoing modern biological treatments of schizophrenia were reviewed. It was noted that since the introduction of chlorpromazine at least 50 neuroleptics had been clinically investigated. While most of these new drugs… are successful pharmacological agents in the control of psychopathological manifestations of schizophrenia, the fact remains that neuroleptics may alter the course but cannot cure the disease.”

AUTHOR’S COMMENTS: This monograph is an expansion of my presentation at a Symposium on Schizophrenia, organized and chaired by Nathan S. Kline, that was held at the Arizona State Hospital  in Phoenix, on November 12, 1971. The material was also presented in my lectures on the Biology of Schizophrenia to postgraduate students in psychiatry, McGill University, at the Douglas Hospital in Verdun, Quebec, during January 1972.

 

June 5, 2014  

            February 13, 2020