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Tuesday, 15.10.2019

Pierre Baumann and Francois Ferrero: (1946 – 1972) An Official Inquiry on the Clinical Research Activities of Roland Kuhn (1912 – 2005)

Preliminary notes

Roland Kuhn: The Discovery of the Tricyclic Antidepresants and the History of Their Use in the Early Years.

PREAMBLE

Roland Kuhn’s brief autobiographic essay, The Discovery of the Tricyclic Antidepressants and the History of Their Use in the Early Years, was adopted from "A History of the CINP," edited by Thomas A. Ban and Oakley S. Ray (Brentwood; 1996, pp. 425-35.) The volume includes the entire “first history series” of the Collegium Internationale Neuropsychopharmacologicum (CINP): "Thirty Years CINP" (Ban TA, Hippius H, eds. Berlin, Springer 1988), "Psychopharmacology in Perspective" (Ban TA, Hippius H, eds. Berlin, Springer 1992), "Towards CINP" (Ban TA, Hippius H,eds. Berlin, Springer 1994) and "The EarlyYears," edited by Thomas A. Ban, Oakley S. Ray and Hanns Hippius that was first published here

In his contribution to Early Years, Kuhn outlines his research with drugs that began in the late 1940s with the study of a substance that was to be introduced with the trade name, Parpanit in the treatment of Parkinson’s disease and continued in the mid 1950s (1956-1957) with his discovery of the-therapeutic effect of imipramine in depressed patients with “vital depressive predisposition” (VDP). He also discusses his early concerns about the possibility that imipramine may have an effect on “cells of propagation” (teratogenicity) and that dependence and addiction may develop in the course of treatment with the drug. Furthermore, he challenges the statistical methodology adapted in clinical research with psychotropic drugs that is focused on the demonstration of therapeutic efficacy, instead of the identification of the clinical characteristics, in terms of psychopathological symptoms of the treatment responsive population to a drug. In this context, he emphasizes that the key to his discovery of imipramine’s “antidepressant” property was his recognition that the presence of VDP -- characterized by “tiredness; feelings of confinement, heaviness and dejection or depression; slowed or obstructed thinking, decision making and interaction; loss of the ability to enjoy oneself and sustain interests; and daily fluctuations with worsening in the morning-- was prerequisite for a favorable effect to treatment.

Kuhn died in 2005. In 2016, an official inquiry was setup in Switzerland, to examine his clinical research activities from 1946 to 1972

Thomas A. Ban

June 8, 2017

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