Thomas A. Ban
Neuropsychopharmacology in Historical Perspective
Education in the Field in the Post-Neuropsychopharmacology Era
Background to An Oral History of the First Fifty Years

Update (Volume Nine): 3a. Interviewee’s Contributions

( Bulletin 71)

            Volume 9 Education transcripts of 19 videotaped biographic interviews. There are four MD, PhDs (Gottschalk, Klein, Pletscher and van Praag), 12 MDs (Ayd, Ban, Berger, Cole, Fink, Hollister, Itil, Janowsky, Levine, Meltzer and Sarwer-Foner) and three PhDs (Gittelman-Klein, Katz and Kornetsky) among the interviewees. The 16 MDs (including the MD, PhDs) include 13 certified psychiatrists, one microbiologist (Berger), one internist (Hollister) and one pharmacologist (Pletscher). The three PhDs are psychologists.

            All interviewees are ACNP members; seven (Ayd, Cole, Fink, Gottschalk, Hollister, Kornetsky and Sarwer-Foner) are Founders; and five (Cole, Hollister, Klein, Meltzer and Simpson) are past-presidents.

            All transcripts in Volume 9 are based on the second interview of interviewees and all but five interviews were conducted at ACNP’s annual meetings from 1994 to 2008.  From the five interviews conducted between annual meetings, four (Berger, Cole, Gottschalk and Hollister) were conducted in Nashville and one (Pletscher) at CINP’s biennial congress in Paris.

            The 19 interviewees were interviewed by 12 interviewers: nine interviewers (Angrist, Belmaker, Braslow, William Bunney, Carpenter, John Davis, Koslow, Leckman and Tamminga), conducted one interview; two (Healy and Tone), conducted two; and one (Ban) six. From the 12 interviewers 10 are peers of the interviewees and two are medical historians (Braslow and Tone).  One of the medical historians (Braslow) is also a  qualified psychiatrist.

            By the time Volume 9 was published six of the interviewees (Ayd, Berger, Cole, Gottschalk, Hollister and Pletscher) had passed away (Ban 2011a; Blackwell 2011).

Contributions of Interviewees

            In the following some contributions of interviewees in Volume 6 to the development of neuropsychopharmacology are reviewed (Ban 2011b).

            In 1947 Frank M. Berger observed that mephenesin has muscle relaxant and tranquilizing effects in animal (Berger 1947). In 1949 he reported on the effect of the substance on spastic and hyperkinetic disorders (Berger and Schwartz 1948). Berger’s determination to synthesize and develop a mephenesin-like drug with a longer duration of action led, in 1955, to the introduction of meprobamate for the treatment of anxiety disorders (Berger 1954). During the 1950s and ‘60s, Berger developed several other structurally similar propanediol preparations to meprobamate, e.g., tybamate (Berger 1977).

            In 1950 Conan Kornetsky was a member of Harris Isbell’s team that reported experimental findings in chronic barbiturate intoxication (Isbell, Altschul, Kornetsky et al. 1950).  In a subsequent report Kornetsky provided more details of his findings on the psychological effects of chronic barbiturate use (Kornetsky 1951). Kornetsky began with his research on the effects of anxiety and morphine on the anticipation and perception of painful radiating thermal stimuli in the early 1950s (Kornetsky 1954). During the following years he extended the scope of his studies to the pharmacology of nociception and in 2006 reported that, using thermal radiation and intra-cerebral electric stimulation, there was no difference in nociceptive threshold and analgesic response to morphine between old and young rats (Crosby, Knapp and Kornetsky 2006). In collaboration with Knapp, Tozier and Pak he also revealed that medial forebrain stimulation enhanced intracranial nociception and attenuated morphine-induced analgesia (Kornetsky, Knapp, Toazier and Pak 2010). 

            In 1954 Turan M. Itil was among the first to publish, in collaboration with Dieter Bente, on the effects of chlorpromazine (Megaphen) on the human EEG (Bente and Itil 1954a). During the 1950s he also reported on the effect of promethazine on phantom pain and on EEG changes with several psychotropic drugs, e.g., reserpine, lysergic acid diethylamide (Bente and Itil  1954b, 1957,  1967). In the 1960s Itil developed “quantitative EEG” with Max Fink and classified psychotropic drugs with the employment of the EEG (Itil, Shapiro and Fink 1968). In the 1970s he extended his research to include the detection of psychotropic properties of drugs. It was in the course of this research that he discovered the  antidepressant properties of mianserin (Itil 1998; Itil, Polvan  and Hsu 1972). By the 1980s Itil also employed “computerized EEG” in predicting treatment response to psychotropic drugs, e.g., response to neuroleptics in schizophrenia (Itil  and Shapiro 1981). He continued his research with “computerized EEG” throughout the 1980s and 1990s.

            In 1955 Alfred Pletscher, a member of Bernard Brodie’s team, in preparation for his new position with Roche, was first to demonstrate, in collaboration with Parkhurst Shore, that reserpine releases serotonin in the brain (Pletscher, Shore and Brodie 1955). In 1956 he also showed that the monoamine oxidase inhibitor, iproniazid, increased cerebral serotonin levels (Pletscher 1956). In the 1960s, as Roche’s research director, Pletscher was involved in the development of benzquinolzines, a series of reserpine-like monoamine depleting drugs with psychotropic effects (Pletscher, Brossi and Gey 1962). He was also instrumental in developing benserazide, an extracerebral decarboxylase inhibitor that enhanced the therapeutic effect of levodopa in Parkinson’s disease (Bartholini, Burcard, Pletsher and Bates 1967). By the late 1970s Pletscher was no longer involved in neuropharmacology research.

            In 1955 Leo E Hollister was one of the first to report on the therapeutic effect of reserpine in the treatment of schizophrenia and of Metrazol (pentylenetetrazol) and Hydergine in nervous and mental disease associated with old age (Hollister 1955; Hollister and Fitzpatrick  1955; Hollister, Krieger, Kringel and Roberts 1955; Hollister, Traub and Beckman  1956).  Hollister was also first to report, in 1961, on withdrawal reaction after chlordiazepoxide discontinuation (Hollister, Montzenbecker and Degan  1961). During the 1960s and ‘70s Hollister was involved in studying the effect of numerous psychotropic drugs. The first edition of Hollister’s monograph, The Clinical Use of Psychotherapeutic Drugs, was published in 1973 (Hollister 1973, 1978). As multi-center studies replaced single center clinical investigations in the 1980s, Hollister gradually withdrew from clinical investigations.

            In 1955 Gerald J Sarwer-Foner was among the first in Canada to study the use of reserpine and other psychotropic drugs in an “open psychiatric setting” (Sarwer-Foner and Ogle  1955). In 1956 he reported that reserpine and chlorpromazine, instead of alleviating, enhanced anxiety in some patients (Sarwer-Foner and Ogle 1956). He attributed the paradoxical effect of these drugs to interference with ego defenses when “activity-passivity” mechanisms are involved (Sarwer-Foner 1957). Throughout the years Sarwer-Foner has maintained that in patients’ response to psychotropic drugs psychodynamic mechanisms play a role (Sarwer-Foner 1960, 1966).

            In 1955 Frank J. Ayd, Jr. published one of the first papers in the United States on the use of chlorpromazine in psychiatric patients (Ayd 1955). He became involved in clinical investigations with psychotropic drugs and in 1958 reported on the differential effect of several phenothiazines (Ayd 1959). In 1960 Ayd was among the first to report on the antidepressant effect of amitriptyline (Ayd 1960). One year later, in 1961, he published his monograph, Recognizing the Depressed Patient (1961a). About the same time, he also published the findings of his survey on neuroleptic-induced “extrapyramidal reactions” (Ayd 1961b). In the mid-1960s Ayd launched the International Drug Therapy Newsletter to speed up dissemination of research findings with psychotropic drugs. In the 1980s Ayd gradually withdrew from clinical investigations and began with the preparation of his Lexicon of Psychiatry, Neurology and Neurosciences. The Lexicon was first published in 1995 (Ayd 1995).

            In 1956 Louis A. Gottschalk reported that in normal subjects response to pipradrol was more dependent on subjects’ personality traits than on any other factor (Gottschalk, Knapp, Ross et al. 1956). Subsequently, in the 1960s, Gottschalk studied the effects of several phenothiazines and benzodiazepines with the employment of his first “content analysis scales” (Glaser, Gottschalk, Fox and Lippsert 1965; Glaser, Gottschalk and Springer 1961; Gottschalk, Glaserr and Springer 1963; Gottschalk, Glaser, Springer et al. 1960).  During the 1970s Gottschalk became involved in pharmacokinetic research and studied the relationship between blood levels and clinical response to psychotropic drugs. It was  in the course of these studies that he identified the metabolites of thioridazine and mesoridazine responsible for the cardiac effects of these drugs (Gottschalk and Merlis 1979). In 1980 Gottschalk reported his findings from toxicological and pathological studies on “drug-involved death” (Gottschalk and Cravey 1980). Throughout the years “content analysis of speech” remained central in Gottschalk’s research. His instrument for “content analysis of speech” was translated into several languages and was used in studies with psychotropic drugs (Gottschalk 1994).

            In 1956 Jonathan O. Cole organized the first conference on Problems in the Evaluation of Pharmacotherapy in Mental Illness (Cole and Gerard 1959). Subsequently, he was the architect of the NIMH collaborative studies on the effectiveness of phenothiazine treatment in acute schizophrenia (National Institute of Mental Health Psychopharmacology Research Branch 1967; National Institute of Mental Health Psychopharmacology Service Center 1964). In 1965 Cole co-authored a paper with Gerald Klerman on the efficacy of imipramine and some other tricyclic antidepressants in depressive illness (Klerman and Cole 1965). During the 1980s he collaborated with George Gardos on tardive dyskinesia research, and with Alan Schatzberg and Joseph Schildkraut in developing a biochemical classification of depression (Cole, Gardos and Bolig  1992; Gardos, Cole and LaBrie  1982; Schatzberg, Samson, Bloomingdale et al 1989). In 1990, with Teicher and Glod, Cole was first to report on the emergence of intense suicidal preoccupation during fluoxetine treatment (Teicher, Glod and Cole 1990).  

            In 1957 Max Fink demonstrated the relation of Δ-activity in the human EEG and behavioral response to ECT (Fink and Kahn 1957).  One year later, in 1958, Fink was among the first to report on the differential effect of antipsychotic, antidepressant and antianxiety drugs on the human EEG and behavior (Fink 1959). In the same year, in collaboration with Shaw, Gross and Coleman, he showed the superiority of chlorpromazine to insulin coma therapy in the treatment of psychosis (Fink, Shaw, Gross and Coleman 1958). During the 1960s and ’70s Fink’s research was focused on pharmaco-EEG, digital computer analysis of the human EEG and EEG classification of psychotropic drugs (Fink 1968, 1998; Fink, Itil and Shapiro 1967). In the 1990s his interest shifted and in 2003, he published with Allan Taylor his monograph, Catatonia, and in 2006, Melancholia   (Fink and Taylor 2006; Taylor and Fink 2003). 

References:

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Ayd FJ. Amitriptyline (Elavil) therapy of depressive reactions. Psychosomatiics 1960; 1: 320-5.

Ayd FJ. Recognizing the Depressed Patient. New York: Grune & Stratton; 1961a.

Ayd FJ. A survey of drug-induced extrapyramidal reactions. JAMA 1961b; 175: 1056-60.

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Bartholini G, Burkard WP, Pletscher A, Bates HM. Increase of cerebral catecholamine caused by 3,4 dihydroxyphenylalanine after inhibition of peripheral decarboxylase. Nature 1967; 215: 852-3.

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May 30, 2019