Saturday, 25.03.2017

Psychiatry for Neuropsychopharmacologists

1. Introduction
Thomas A. Ban

Neuropsychopharmacology is dedicated to the study and treatment of mental disorders with the use of centrally acting drugs. Its birth in the mid-1950s was  triggered by the introduction of effective pharmacological treatments for mental disorders; recognition of the importance of chemical mediation at the site of  the neuronal synapse;detection of the presence of several neurotransmitters in the brain; and the construction of the spectrophotofluorometer, an instrument with sufficient resolution power to measure drug-induced changes in the concentration of monoamine neurotransmitters involved in neuronal transmission at the synaptic cleft in the brain. Spectrophotofluorometry provided direct access to detect biochemical changes which might be responsible for a psychotropic drug’s therapeutic effect (Ban 2004).

The new discipline has grown on the premise that neuropharmacological research on the mode of action of psychotropic drugs with well-defined therapeutic indications will generate the necessary knowledge about the pathophysiology and biochemistry of the mental disorder that will guide research to develop more effective and selective pharmacological treatments (Ban 2006). An essential prerequisite of neuropsychopharmacological research is a well-defined treatment responsive population to a psychotropic drug, i.e., the sub-population within a diagnostic group to which the drug’s efficacy can be attributed. Yet, when the introduction of lithium, chlorpromazine and imipramine, the first psychotropic drugs with demonstrable therapeutic efficacy in manic-depressive psychosis, schizophrenia and endogenous depression, respectively, focused attention on the pharmacological heterogeneity within these diagnoses in responsiveness to treatment, no attempt was made to examine whether employment of diagnoses in Karl Leonhard’s  (1957)  classification could identify the  treatment responsive  subpopulations to these drugs.

Leonhard’s classification was published in 1957, just about the time of Roland Kuhn’s (1957) discovery of imipramine’s therapeutic effect in some patients with endogenous depression. It is the final product of a tradition in psychiatry which began with Carl Wernicke and passed to Leonhard via Karl Kleist (Kleist 1947; Wernicke 1900). In Leonhard’s classification, Kraepelin’s (1896, 1899, 1903-4, 1908-15) diagnostic concepts of manic-depressive psychosis and dementia praecox (schizophrenia) were deconstructed into four classes of disease with a total of 35 diagnoses.

As the treatment responsive subpopulations to lithium, chlorpromazine and imipramine have still not been identified, INHN is launching an educational program in preparation for research to examine whether using clinical end-points based on the Wernicke-Kleist-Leonhard tradition, and especially on Leonhard’s classification, could identify pharmacologically more homogeneous populations to these prototype drugs than with Kraepelinian diagnoses.

References:

Ban TA. Neuropsychoharmacology and the history of pharmacotherapy in psychiatry. In Ban TA, Healy D, ShorterE, eds. Reflections on Twentieth – Century Psychopharmacology. Budapest: Animula; 2004, pp. 704-20.

Ban TA. Concluding remarks. In Ban TA, Ucha Udabe R, editors. The Neurotransmitter Era in Neuropsychopharmacology.  Buenos Aires: Polemos; 2006, pp. 266-74.

Kleist K. Fortschritt der Psychiatrie. Frankfurt: Kramer; 1947.

Kraepelin E. Psychiatrie. Ein Lehrbuch für Studierende und Ärzte. 5 Aufl. Leipzig: Barth; 1896.

Kraepelin E. Psychiatrie. Ein Lehrbuch für Studierende und Ärzte. 6 Aufl. Leipzig: Barth; 1899.

Kraepelin E. Psychiatrie. Ein Lehrbuchfür Studierende und Ärzte. 7 Aufl. Leipzig: Barth; 1903-1904.

Kraepelin E. Psychiatrie. Ein Lehrbuch für Studierende und Ärzte. 8 Aufl. Leipzig: Barth; 1908-1915.

Kuhn R. Uber die Behandlung depressives Zustande mit einem iminodibenzylderivat (G22355). Schweiz Med Wochenschrift 1957; 87: 1135-40.

Leonhard K. Aufteilung der endogenen Psychosen. Berlin: AkademieVerlag; 1957. 

Wernicke C. Grundrisse der Psyhiatrie. In Klinischen Vorlesungen. Leipzig: Barth; 1900.

 

Thomas A. Ban
December 24, 2015