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Saturday, 24.06.2017

HISTORY OF THE CINP

by Thomas A. Ban

HISTORICAL BACKGROUND

Developments which led to neuropsychopharmacology and the CINP began in 1952 with the introduction of chlorpromazine in psychiatry. The therapeutic and commercial success of chlorpromazine generated interest within the pharmaceutical industry in developing drugs with psychiatric indications. By the end of the 1950s there was, a rapidly growing number of new psychotropic drugs and the scope of psychopharmacology, a term coined by Macht in 1920, was extended from the study of psychotomimetics and model psychosis to include the study of psychotherapeutics and their effectiveness in mental illness.  The difficulties encountered in showing the efficacy of chlorpromazine in schizophrenia, and of imipramine in depression, focused attention on the heterogeneity of responsiveness to pharmacological treatment in schizophrenia and depression. Yet, instead of developing a methodology for resolving this heterogeneity, sensitive instruments were developed to detect and demonstrate antipsychotic and antidepressant effects. With the employment of the new methodology, “efficacy studies” were to dominate research in psychopharmacology to-date.

Simultaneously with the introduction of the first set of effective drugs in the treatment of mental illness, there was a shift in the understanding of the nature of synaptic transmission from a purely electrical (physical) to a chemically-mediated event, and by the end of the 1950s six neurotransmitters had been identified in the central nervous system.  Recognition of chemical mediation at the site of the synapse, coupled with the introduction of the spectrophotofluorimeter, led to the development of neuropharmacology, the scientific discipline that deals with the detection and the identification of structures responsible for the psychotropic effects of centrally acting drugs. Spectrophotofluorimetry provided direct access to the detection of the biochemical changes which might be responsible for the therapeutic effects.

Developments in pharmacotherapy, psychopharmacology and neuropharmacology triggered the development of neuropsychopharmacology, the scientific discipline dedicated to the study and treatment of the pathophysiology of mental syndromes with the employment of centrally acting drugs. Recognition that one of the essential prerequisites of successful neuropsychopharmacological research is a continuous dialogue between clinicians (psychiatrists) and basic scientists (pharmacologists) created a need for the founding of an association which would provide a suitable platform for interaction among the different disciplines of the new field.

THE   FOUNDING  OF CINP (Milan, May 1957 – Zurich, October 1957)

To start the dialogue between clinicians and basic scientists an International Symposium on Psychotropic Drugs was hosted by the University of Milan in May 1957. It was chaired by Emilio Trabucchi, the professor of pharmacology, and organized by Silvio Garattini, a young pharmacologist in the department of pharmacology of the University. It was during the Milan Symposium that Wolfgang de Boor, the author of the monograph Pharmacopsychologie und Psychopathologie, and Corneille Radouco-Thomas, a pharmacologist from the University of Geneva, proposed the founding of an “international association” to provide a forum for interaction between clinicians and basic scientists for the study of psychotropic drugs..

The formal inauguration of the Collegium Internationale Neuro-Psychopharmacologicum (CINP), a name coined by Radouco-Thomas, took place four months after the Milan Symposium, on September 2, 1957, during the 2nd World Congress of Psychiatry, at a dinner meeting, hosted by Ernst Rothlin, in the buffet of the Zurich railway station. By the end of the dinner Rothlin, a former director of Sandoz, a major Swiss pharmaceutical company, was elected president, W.A. Stoll, treasurer, Corneille Radouco-Thomas and Herman Denber, secretaries, and Pierre Deniker and Philip Bradley, councilors. The 32 invited guests became the founders of CINP.

INTERACTION: BASIC SCIENTISTS AND CLINICIANS (Rome 1958 – Tarragona 1968)

The primary objective of the Collegium was to organize meetings for its members at least once every two-years “to consider and discuss matters related to neuropsychopharmacology and through the organization encourage and promote international scientific study, teaching and application of neuropsychopharmacology” (Constitution, Article II). There was disagreement regarding membership between the two main players in the founding, Rothlin and Trabucchi, in which Rothlin prevailed, and membership was restricted to those actively involved in the new field instead of being open to all interested in the new drugs. Nonetheless, it was decided that congresses should alternate between   “open” meetings with free attendance for everyone interested in the field, and “closed” meetings with attendance restricted to CINP members and their invited guests. The idea was that open meetings with larger audiences would provide a forum to communicate new developments in neuropsychopharmacology, whereas closed meetings would allow interaction among the disciplines and provide feedback from clinicians to basic scientists and vice versa. 

The 1st CINP Congress was an open meeting in 1958 in Rome with about 500 participants, and the 2nd a closed meeting in 1960 in Basle. It was at the Basle meeting that Arvid Carlsson, a Swedish pharmacologist who was to receive the Nobel Prize, presented his findings on selective changes in brain monoamines and especially of catecholamines with psychotropic drugs, providing the theoretical framework which was to dominate neuropsychopharmacology for well over two decades. It was also at the Basle meeting that Fritz Freyhan, one of the American pioneers of psychopharmacology, called for a “critical examination” of the commonly held belief that there is a linear relationship between neuroleptic potency and therapeutic effects. Listening to Freyhan’s “clinical feedback” that “compounds showing higher frequencies of hyperkinetic syndromes have higher failure rates” in treatment could have prevented the detour in the pharmacotherapy of schizophrenia that led to a high prevalence of tardive dyskinesia  in neuroleptic treated patients.

In keeping with recommendations, the 3rd Congress in 1962 in Munich was open, and the 4th in 1964, in Birmingham, England, closed.. The Birmingham meeting was devoted to one topic, The Mode of Action of Psychotropic Drugs and Its Implications for the Pathophysiology of Psychotic Disturbances. It was uniquely structured in that the first day was dedicated to a plenary session in which speakers with different background, such as Eysenck, a psychologist, Brucke, a pharmacologist, Schleidt, an ethologist, and Selbach, a psychiatrist, introduced the problem from their own point of view; the second and third days were given to discussion in working groups, and the fourth and final day to a second plenary session at which deliberations of the working groups were summarized in reports.

Many of those who attended the Birmingham Congress felt that the format of the meeting was optimal for interaction and should have been adopted at future meetings. But this did not happen, and by the end of the 1960s --after another open meeting in 1966 in Washington, DC, and another closed one in 1968 in Tarragona  -- the difference between closed and open meetings started to wither away.

COMMUNICATION OF FINDINGS (Prague 1970 – Florence 1984)

During the 1970s pharmacotherapy with psychotropic drugs became the primary form of treatment in mental illness; psychiatrists involved in psychopharmacology were becoming an integral part of the psychiatric establishment; and CINP congresses were transformed into meetings with less and less emphasis on feedback, and with more and more sessions dedicated to presentations in newly emerging areas of research with little, if any time left for interaction. Thus, the 7th CINP Congress in 1970, in Prague, Czechoslovakia,  included symposia on lithium with special attention on the prophylactic treatment of bipolar disorder, and on the evaluation of anxiolytic drugs; the 8th in 1972, in Copenhagen, Denmark, on the pharmacotherapy of sexual disorders, and on the long-term effects of psychotropic drugs; the 9th in 1974, in Paris, France, on the effect of neurotropic drugs on cyclic AMP in the brain, and on genetics in psychopharmacology; the 10th   in 1976, in Quebec City, Canada, on geriatric neuropsychopharmacology, and on the interrelationship among neurotransmitter systems; and the 11th , in 1978, in Vienna, Austria on endorphins and  narcotic antagonists in the treatment of schizophrenia, and on the role of GABAergic mechanisms in the action of benzodiazepines.

By the end of the 1970s it was recognized that pharmacotherapy based on hypotheses derived from studies on the mode of action of psychotropic drugs, such as the catecholamine hypothesis of depression, or the dopamine hypothesis of schizophrenia, did not work. In spite of this, CINP congresses have become increasingly dominated by neuropharmacology, driven by technological progress, such as the development of receptor binding assays, which opened the path for the determination of the norepinephrine and serotonin blocking potencies of drugs, and the identification of receptor subtypes, which led to the delineation of the receptor profiles of neuroleptics and antidepressants.

By the early 1980s basic research in neuropharmacology was extended from cerebral monoamines to include neuropeptides and prostaglandins. The 12th CINP Congress in 1980, in  Goteborg, Sweden, reflected  “the shift from neurotransmitter biochemistry at the synaptic cleft to receptor research”; the 13th CINP Congress in 1982, in Jerusalem, Israel, “documented the effort to understand mental disease in terms of molecular processes”; the 14th CINP Congress in 1984, in Florence, Italy, reinforced the belief that employment  of molecular neurobiology “could lead to research that will transcend the existing boundaries of neuropsychopharmacology”; and at the 15th Congress in 1986, in San Juan, Puerto Rico, Floyd Bloom  in his plenary lecture described a Brave New World that will be known in terms of cell function at the molecular level, and a galaxy of transmitters and their modifiers “signaling” to each other.

COMMUNICATION OF INTERPRETATIONS (San Juan 1986 – Paris 2004)

In contrast to the major advances in neuropharmacology, there was little progress made in clinical psychopharmacology after the 1970s. The methodology of clinical psychopharmacology with its sensitized rating scales, and consensus-based diagnostic end-points has the capability only to demonstrate therapeutic efficacy but not to translate the differential receptor profiles of drugs into therapeutic profiles relevant to patients and treatment. Idiosyncratic classifications are covered up by consensus-based classifications; signs and symptoms which are relevant to diagnosis are dismissed by sensitized rating scales. Multi-center, centrally-coordinated clinical investigations with sample-sizes determined by power statistics lead to semi-finished psychotropic drugs without any guidance in predicting which form or sub-form of illness is responsive to the drug.

By the late 1980s the gap between neuropharmacology and psychopharmacology grew so wide, that without interpretation by neuropsychopharmacologists, it could not be bridged. The objective of CINP congresses shifted from interaction and feedback between clinicians and basic scientists, to interpretations about the mode of action of psychotropic drugs. 

The shift of emphasis in CINP meetings from communication of findings to communication of interpretations began in 1986 at the end of the presidency of Ole Rafaelsen, a Danish neuropsychopharmacologist, with the presentation of industry- supported Travel Awards to Young Investigators to facilitate their participation in the Congress, and with the first president’s reception and dinner, supported by Bristol-Myers-Squibb, at the San Juan Congress..

The transformation of the college continued with tightening the ties with the drug industry and with national (sister) organizations in neuropsychopharmacology during the presidency of William Bunney, a prominent American neuropsychopharmacologist. It lead in 1998 to the implementation of corporate membership of pharmaceutical firms, and to the starting of a meeting among presidents and secretaries of the sister organizations at the Munich Congress, that was to become the corresponding- organizations luncheon meeting, supported by Hoechst Marion Russell, now Aventis. 

The changes culminated with a past-presidents symposia --as well as with a past-presidents and meeting-organizers luncheon-- during the presidency of Alec Coppen, a pioneer British neuropsychopharmacologist, and with the organization of regional meetings during the presidency of Lewis Judd, a former director of the National Institute of Mental Health of the United States. It was also during the presidency of Coppen that the first award for recognizing excellence, the Max Hamilton Prize, was established with the support of Bristol-Myers Squibb and presented in 1990 at the Kyoto Congress to Steven Paul, vice president of research of Eli Lilly, an American pharmaceutical company.

ORGANIZATIONAL CHANGES (Melbourne 1996 – Paris 2004)

To correspond with the changes in the activities of the  organization, CINP’s Constitution and By Laws were amended several times from 1986 to 2004, with the last amendment approved in April 2002. A move toward democratization started after the Melbourne Congress in 1996 during the presidency of Claude de Montigny, a Canadian neuropsychopharmacologist, with the nomination of a slate of two --instead of one -- candidates for each of the five offices on the executive, and for each of the 10 positions on the council. During the presidency of Helmut Beckmann, a prominent German psychiatrist, CINP became legally incorporated. By the time of the Brussels’ Congress in 2000, the organization had been a legal entity registered in Switzerland with domicile in Zurich.

The first president of CINP in the new millennium, and its first elected president, was Eugene Paykel, a prominent British psychiatrist. During his tenure from 2000 to 2002, a regional structure was established with “conveners” responsible for the coordination of activities in the different geographic regions; and a Central Office was set up for continuity and the smooth operation of the college. Paykel was succeeded by Herbert Meltzer, an American neuropsychopharmacologist, who was instrumental in complementing the central office with a Meeting Organizer Group which, if successful, would channel back to CINP’s treasury the money spent on congress organizer business companies. Establishment of the Meeting Organizer Group could be the first step in resolving the situation that CINP shares profit from the revenues generated by meeting with the host  organization in the proportion of 3 (CINP) to 1 (host) because it does not take financial responsibility for any of its meetings, including the biennial congresses.

MY ACTIVITIES IN CINP

At the time I was elected a fellow of CINP in 1962 I was in charge of an early clinical drug evaluation unit at the Verdun Protestant Hospital, a psychiatric inpatient facility in the suburbs of Montreal, Canada.  Becoming a member of the college made it possible for me to get access to information in the new field and to interact with those who created the drugs we were studying in our research. It was about 30 years before the “computer age”; information was scarce and difficult to get.  There were only two journals in the field, Psychopharmacologia, founded by Rothlin and Wikler in 1958, and International Neuropharmacology (which was to become Neuoropsychopharmacology), founded by Brodie , Costa and Radouco-Thomas a couple of years later..

I served on CINP’s executive committee from 1970 to 1974 as secretary, from 1974 to 1976 as vice president, and from 1978 to 1986 as treasurer. During my service on the executive, the membership of CINP grew from 200 to over 600, far beyond the allowed 15% from one congress to another, with virtually all members attending each congress, and the general assembly at the congress. I took over the treasury from Paul Janssen with less than $ 40,000, and passed it to Lauren Maitre with over $100,000. The organization in those years was operated on a shoestring. It was a very different organization from the CINP today which has well over a million dollars invested, disburses expenses for several offices, organizes larger and larger meetings with an attendance of only about one-quarter of its members, has general assemblies with hardly enough members attending to provide a quorum to vote, and a slow growth of membership in spite of considerable efforts for recruitment.

What was to become CINP’s history committee started as an informal collaboration (committee) between Ole Rafaelsen, Hanns Hippius and I at the tail end of Rafaelsen’s presidency in 1986. Our plan was to reconstruct the history of CINP from eye-witness records before it is too late. Ole died shortly after, but Hippius and I continued with the work and from 1986 to 1994 we prepared a series of four booklets on the history of CINP.  Shortly after the fourth booklet was completed the committee published a 457-pages book with the title A History of the CINP which included the four booklets, under one cover supplemented with some complementary information on the history of the college from the San Juan Congress in 1986 to the Sydney Congress in 1994.   

In 1996 the history committee was extended to include 9 members, and strengthened with the inclusion of David Healy, a psychiatrist trained in neuropharmacology who has challenged some of the practices of neuropsychopharmacology, and Edward Shorter, a social historian with a background in the history of psychiatry and a special interest in psychopharmacology. From 1996 to 2004 the committee published the CINP International Photo Archives in Neuropsychopharmacology 2000, the Selected Writings of Joel Elkes, one of the CINP-Pfizer pioneers, and a series of four books on The History of Psychopharmacology and the CINP, As Told in Autobiography. The series provides information on the origin of the discipline and the organization, on the place of the organization in society and among the other professional societies, on the direction in which the field and the organization is moving; and on possible alternatives to this direction. Although prepared primarily as a source book, the series should be of interest to all those involved in research and teaching neuropsychopharmacology.

CONCLUSIONS

By the end of the 20th century pharmacotherapy with psychotropic drugs has become the primary form of treatment in all the various psychiatric disorders from sexual dysfunction to the dementias. By supplying drugs with demonstrated therapeutic efficacy, together with information on their pharmacological profile, mode of action and clinical effects, the pharmaceutical industry was instrumental in reintegrating psychiatry with the other medical disciplines. Furthermore, by providing financial support for research from genetics through neuropharmacology to brain imaging, industry succeeded in establishing psychopharmacology as the dominant paradigm in psychiatry around the world. With the development of neuropsychopharmacology, the term “psychiatry” with its implicit separation of the afflictions of the “mind” from the diseases of the “body,” has become anachronistic and ready to be replaced in the new millennium.

Simultaneously with this development, CINP has grown into a prosperous organization which is incorporated in Switzerland and has a central office in Nashville, with a membership from all six continents, approaching 1000. The organization has played a role in converting the thinking of psychiatrists from psychological to biological; in facilitating the development of a cadre of neuropsychopharmacologists; and in providing a forum for the communication of new developments in the pharmacotherapy of psychotropic drugs. In 1957, at the time it was founded, CINP was the only organization in the new field, and the pharmaceutical industry was hoping for interaction through the organization among the different isolated disciplines involved with neuropsychopharmacology. It was also seeking guidance by feedback through the translation of pharmacological profiles into clinical effects, in order to develop new drugs. In the absence of clinical feedback, by the 1970s neuropharmacology became the driving force in neuropsychopharmacology, and CINP became the platform for the communication of findings on psychotropic drug development to an international audience. The increasing sophistication in neuropharmacology, without a parallel development in the methodology of clinical investigations, created a widening gap between neuro- and psychopharmacology. By the mid-1980s clinical interpretations of neuropharmacological findings were filling in the missing information from translational research. Translational research is dedicated to the establishment of relationships between dfindings in different areas of the field whereas interpretations in neuropsychopharmacology  make neuropharmacological research findings applicable for clinical use before establishing a definite relationship between the findings and clinical effects.

In 2004 by the time Brian Leonard succeeded Herbert Meltzer as president, CINP had expanded its membership and evolved into its present form. Yet, CINP was no longer a unique organization dedicated to the communication of “translational  research”,  but one of many organizations dedicated to the communication of clinical interpretations in neuropharmacological research.

Confronted with this reality CINP may continue in the direction set in the late 1980s – organize larger and larger meetings and become the most powerful organization in the communication of interpretations in neuropsychopharmacology – or return to its roots, dedicated to the discussion and communication of findings in translational research.

Thomas A. Ban
December 19, 2013