Biological Indicators in Psychiatrywas prepared for and presented by Dr. Heinz E. Lehmann at the MEDAC meeting, held in Madrid, Spain, on March 20-21, 1975.

“Chlorpromazine: The story of phenothiazine derivatives, their clinical indications, the incidence and management of untoward effects, and a proposed rationale of its action” was written by Heinz E. Lehmann in the late 1950s

This paper with the title, “Clinical Models of Response to Treatment - Historical Perspective”, was presented by Heinz E. Lehmann at the 6^th Conference on Bio-Clinical Interface: New Prospects in Psychopharmacology. The Conference was held on September 28, 1989, in Rouffach, France. 

Delirium: Historical Aspects was presented by Heinz E. Lehmann at a meeting, held at St. Mary’s  Hospital, Montreal, Quebec, Canada on April 28, 1995.

This Discussion by Heinz E. Lehmann of Eli Robins’ paper on Primary and Seondary Affective Disorders.  A Classification of Description, Research  and Management of Mood Disorders, was presented at the Sixtieth Annual Meeting of the American Psychopathological Association, February 13^th-14^th , 1970, at the Hilton Hotel in New York City. 

Discussion of Jack H. Mendelson’s paper on Alcoholism, Aggression and Androgen Function, was presented by Heinz E. Lehmann at the Meeting on Biomedical Research in Drug Abuse Problems, in Halifax, Nova Scotia, Canada, held August 29-30, 1974.

This paper was presented by Heinz E. Lehmann as a Discussion of the paper ”The treatment of depression”  by Professor Pierre Pichot, at a symposium in  St. Moritz, Switzerland, in January 1974.

This paper was presented by Heinz E. Lehmann as a Discussion of the Symposium on Divergent Motivations for Creativity in Art and Science at the International Congress of Applied Psychology, in Montreal, Quebec, Canada, on July 29, 1974.

“Dreaming about Mental Health” was presented by Heinz E. Lehmann at a meeting of the Canadian Mental Health Association Quebec Division, in Quebec City, Quebec, on November 20, 1992, and at a meeting of the Manitoba Mental Health Association, in Winnipeg,Manitoba on November 3, 1994. 

Harlem Valley Revisited was presented by Heinz E. Lehmann at the Harlem Valley Psychiatric Center on June 17, 1988, on the occasion of receiving the year’s Distinguished Scholar’s Award of the Center and of the New York Medical College.

“Historical Evolution of Antidepressant Drugs” was presented by Heinz E. Lehmann on April 23, 1986, in Phoenix, Arizona.

No More Surprises in Psychiatry? was presented by Heinz E. Lehmann at Hopital Louis LaFontaine, in Montreal, Quebec, Canada, on April 2, 1986.

Perspectives in Psychosurgerywas presented by Heinz E. Lehmann at the Hahnemann Symposium on Psychosurgery, held in Philadelphia, Pennsylvania, USA, on June 17, 1972. (References incomplete)

“Depression: Somatic treatment methods, complications – failures” was presented by Dr. Heinz E. Lehmann at the 13^th Annual Meeting of the American College of Psychiatrists, in Coronado, California, held from January 28 to February 1, 1976.  

The Anatomy of Research Funding: The State Component was presented by Heinz E. Lehmann at the Meeting of the American Psychiatric Association in New York City, May 15, 1990.

“The Impact of the Psychopharmacological Revolution on Psychiatry” was presented by Heinz E. Lehamann at  the Clarke Institute of Psychiatry, in Toronto, Ontario, Canada, in May (21-23), 1986.

The Mental Hospital – Monster, Fossil or Utopiawas presented by Heinz E. Lehmnn  at  the Fourth Biennial International Film Festival, 1978, held in San Antonio, Texas, USA, September 15-17, 1978.

The psychopharmacological treatment of schizophrenia was presented by Heinz E. Lehmann at the 129^th Annual Meeting of the American Psychiatric Association, Miami Beach, Florida, USA, May 10-14, 1976.

Types and Characteristics of Objective Measures in Psychiatry was presented by Heinz E. Lehmann at the Biometrics Research Workshop on Objective Indicators of Psychopathology, held February 13-15^th, 1968, at the Sterling Forest Conference Center, in Tuxedo, New York, USA.

“What is wrong with getting old“, was written by Heinz E. Lehmann in the mid-1990s. At the time, Lehmann, born in 1911, was in his mid-80s. The exact date when it was written and where it was presented by him is not known.

Heinz E. Lehmann and Thomas A. Ban

Early Clinical Drug Evaluation Unit
ECDEU

Progress Report
1961-1963

CONTENTS

1. Background
2. QPRA Symposia and Publications
3. Report
4. References

1. BACKGROUND

Early Clinical Drug Evaluation Units                   

To help clinical investigators in their research of studying psychotropic drugs, the Psychopharmacology Service Center (PSC) of the US National Institute of Mental Health, was created in 1956. The objectives of the PSC were to support clinical and preclinical research with potentially psychotropic substances, act as an information and communication center for these drugs, and extend technical consultation to people working in psychopharmacology.

According to Dr Jonathan O. Cole, the founding director of PSC, “A great majority of clinical research on new psychotropic drugs has been carried out by investigators at public mental hospitals receiving small amounts of support from the pharmaceutical industry. This work has not been extensive and has resulted in most drugs being released by the United States Food and Drug Administration (FDA) for general clinical use with only a small number of uncontrolled studies with variable quality. The absence of well organized and well supported units carrying out early clinical drug studies may have contributed to the slowness with which new have been developed in recent years.”

To facilitate the clinical development of psychotropic drugs, and to improve the quality of clinical investigation funds were provided via the PSC to clinical research units, to be referred to as Early Clinical Drug Evaluation Units (ECDEU), in which drugs with psychotropic potential, on the basis of preclinical findings could be investigated before their approval for general use by the FDA. Thus, the ECDEU program involved government funding of research units around the country primarily to do Phase II and Phase III clinical trials with compounds.  The units had essentially two functions: (1) to investigate new, potentially psychoactive drugs and (2) to advance “methodology” by devising more efficient ways of evaluating them. Federal research grants were given on a five-year renewal basis with considerable latitude afforded to the investigator as to the use of his/her funds and as to the compounds he/she wished to investigate.

Within one year of the announcement of the Program in 1960, there were 12 investigational units in operation. By the second annual meeting of the investigational units in January 1962, there were 15 units.  

Our Early Clinical Drug Evaluation Unit at the Verdun Protestant Hospital (now Douglas Hospital), a psychiatric inpatient facility in the outskirts of Montreal (Quebec, Canada), was funded in November 1961. Our first Progress Report, submitted in December 1963, provides a detailed account of its operation, including the drugs employed and the assessment instruments used in their evaluation during its first two-years. A copy of the original report can be found in the ACNP-UCLA Archives at the Louise M. Darling Biomedical Library of the University of California, Los Angeles Campus.   

2. QPRA SYMPOSIA AND PUBLICATIONS

Activities in our Early Clinical Drug Evaluation Unit program stimulated interest in clinical research with psychoactive drugs in the Province of Quebec, Canada, and were instrumental to the founding of the Quebec Psychopharmacological Research Association (QPRA).

The chain of events that led to the founding of the QPRA began in the summer of 1963, when about 20 people, involved in research in psychopharmacology in the Province met in the Medical Library of the Verdun Protestant Hospital (VPH), to discuss possible collaboration in clinical investigations. It was in the course of this meeting that Ban proposed the founding of an association that was to become the Quebec Psychopharmacological Research Association (QPRA). Three month later, in October the same year, the same group met again at the same place, and founded the QPRA: Heinz Lehmann, at the time clinical director of VPH, was elected president, and Ban, at the time chief of the clinical research service at VPH, executive secretary. The primary objective of the Association was to improve standards in clinical psychopharmacological research by facilitating discussion and communication of research findings through symposia and colloquia (Ban, 2004).

The Butyrophenones in Psychiatry

The first QPRA symposium was held on January 10, 1964, at Hôpital des Laurentides, a psychiatric inpatient facility, in L’Annonciation, Quebec with nearly 100 participants. It was the first North American symposium dedicated to the butyrophenones, with special reference to haloperidol, a substance which in the early 1960s was already extensively used in the treatment of schizophrenia in Europe, but was still little known in North America. Five of the 12 presentations in the symposium were based on findings in our ECDEU program (Ban, 1964; Ban and Stonehill, 1964; Lehmann, Ban, Matthews and Garcia-Rill, 1964; St. Jean, Lidsky, Ban and Lehmann, 1964; Warnes, Lee and Ban, 1964). The proceedings of the symposium were published in 1964 with the title The Butyrophenones in Psychiatry (Lehmann and Ban, 1964). Publication was supported by McNeil Pharmaceuticals, the Company that was to become haloperidol’s Canadian distributor.

Trimipramine, a New Antidepressant

The second QPRA event was held on May 28, 1964 at Hôpital Sant-Jean-de-Dieu (now Hôpital-H Louis Lafontaine), a psychiatric inpatient Facility in Montreal. It was the first North American colloquium on trimipramine, a tricyclic dibenzazepine, in which imipramine’s 5-[3-(dimethylamino) propyl]-10, 11-dihydro-5H-dibenz [b,f] azepine side chain was replaced by a 1-(3-dimethylamino-2-methylpropyl)-10,11-dihydro-5H-dibenz [b,f] azepine side chain. The drug was different also pharmacologically from the parent substance. At the time of our symposium, trimepramine was already in use in France for depression, but the information discussed at the colloquium was based on the first studies with the drug in North America. Four of the 13 presentations in the colloquium were based on findings in our ECDEU program (Ban, 1964; St.Jean, Ban and Noe, 1964; Erutku, Ban and Lehmann, 1964; Lehmann, Kral, Ban, Ast, Barriga and Lidsky, 1964). The proceedings of the colloquium were published by QPRA with the title Trimipramine a New Anti-Depressant (Lehmann, Berthiaume and Ban, 1964). Publication was supported by Rhône-Poulenc, the company that was to become trimipramine’s Canadian distributor.   

Toxicity and Adverse Reaction Studies

The next three meetings of the QPRA were dedicated to toxicity studies and adverse reactions with psychotropic drugs. The first of these meetings was held on March 25, 1965, at the Allan Memorial Institute of Psychiatry, the primary teaching facility of McGill. It was devoted to the toxicity studies required for the registration of psychoactive drugs in Canada. The second meeting was held on April 3, 1965 at the Douglas Hospital (formerly VPH). It dealt with skin pigmentation with chlorpromazine, encountered in Canada, primarily in the Provincial Mental Hospital in Essondale (British Columbia) and in our hospital (Ban and Lehmann, 1965). The third meeting was held on June 4, 1965, at Hôpital des Laurentides. It was the first meeting at which electrocardiographic changes with psychoactive drugs were reviewed and cardiac conductance changes induced by thioridazine were discussed (Ban and St.Jean, 1965).  The proceedings of these three meetings were published in one volume by QPRA with the title Toxicity and Adverse Reaction Studies with Neuroleptics and Antidepressants (Lehmann and Ban, 1965).

The Thioxanthenes

A fourth meeting of the QPRA, the proceedings of which was published, was held on June 21, 1967 at the Douglas Hospital. It was the first North American symposium on the thioxanthenes at which findings with chlorprothixene and clopenthixol, substances developed in Europe, and thiothixene a substance developed in North America, were presented and discussed. In addition to investigators from the Province, investigators from several Early Clinical Drug Evaluation Units, including Max Fink, Barbara Fish, Don Gallant, Burt Goldstein, Sid Merlis,  Burt Schiele, George Simpson and Art Sugerman, participated in the meeting. We reviewed our    findings in a series of studies with chlorprothixene, clopenthixol and thiothixene, in one paper (Lehmann and Ban, 1969b). It included also findings from studies with thiothixene, which were conducted later than the period covered in our 1961-1963 Progress Report (Lehmann and Ban, 1969a). The proceedings of the symposium were published by S. Karger AG Basel (Switzerland) in 1969 in their series, Modern Problems of Pharmacopsychiatry (Lehmann and Ban, 1969a).   

References

Thomas A. Ban

July 4, 2013

3. REPORT