Carlos Morra and Mateo Kreiker: Psychopathology
2. Thomas A. Ban: Development of psychopharmacology*
Psychopharmacology is the scientific discipline that is dedicated to the detection of psychopathologic symptoms and syndromes and the identification of nosologic entities that are affected by psychotropic drugs (Ban 1996). The term “psychopharmacology” was coined in 1920 by David Macht, an American pharmacologist, to describe the effects of drugs on psychometric performance tests; but the roots of the discipline were in the 1845 discovery of Moreau de Tours, a French psychiatrist, that the effects of “dawamsec,” an electuary of hashish, were different in the depressed (melancholic) than in the regressed (“aliéné stupide”) and in the demented. In the 1940s, with the availability of lysergic acid diethylamide, research in psychopharmacology was extended to include the “model psychoses,” psychopathologies induced by psychotropic drugs, with the hope that they would provide the key for the understanding of naturally occurring psychoses. In the 1950s, with the rapidly growing number of psychotropic drugs in the pipelines of the pharmaceutical industry, research in psychopharmacology was further extended to efficacy studies with the new compounds.
Introduction of psychotropic drugs in the 1950s focused attention on the differential responsiveness to the same drug within the same diagnostic category. The pharmacological heterogeneity within the diagnoses created difficulties for the pharmaceutical industry in demonstrating the therapeutic effectiveness of drugs and for psychiatrists in prescribing the new drugs in a predictable manner. Academic psychiatry was confronted with the need to resolve the heterogeneity within the diagnostic categories by re-evaluating psychiatric nosology and to develop a pharmacologically relevant classification of mental illness. But this did not happen. Instead, a statistical methodology, the randomized clinical trial, was adopted for the demonstration of therapeutic effectiveness in pharmacologically heterogeneous diagnostic populations. Consequently, semi-finished psychotropic drugs have been released for clinical use without the delineation of their therapeutic profile, detection of their differential effects or the benefit of orientation points given by clinical psychopharmacological research to predict in which patients they might have therapeutic effects.
There are two essential prerequisites for the adoption of a statistical methodology for the demonstration of therapeutic effectiveness: rating scales, which can detect and document changes, and diagnostic end-points, which can be reliably identified. It was in response to the need for documenting changes that in the early 1970s a German-speaking academic group developed a Manual for the Assessment and Documentation of Psychopathology (Angst, Battegay, Bente et al. 1969; Guy and Ban 1982; Scharfetter 1971); a Swedish academic team constructed a Comprehensive Psychiatric Rating Scale (Asberg, Perris, Schalling and Sedvall 1978); and William Guy (1976) in the United States assembled rating scales for the assessment of change and published them in the Early Clinical Drug Evaluation Units manual which was to become the most important source book of scales for efficacy studies with psychotropic drugs.
The need for diagnostic end points that can reliably be identified was met by the Third Edition of the Diagnostic and Statistical Manual (DSM-III) of the American Psychiatric Association, published in 1980. DSM-III, the first consensus-based classification of mental illness with operationalized diagnostic criteria, was so successful that by the mid-1980s it replaced all other diagnostic classifications in the clinical development of psychotropic drugs
The adoption of a statistical methodology in psychiatry for the study of therapeutic efficacy had a major impact on academic psychiatry by providing a means to evaluate the effectiveness of various treatment modalities. It was on the basis of findings in these evaluations that pharmacotherapy became the primary form of treatment in schizophrenia and mania in the 1960s, in depression and bipolar disorder in the 1970s, in the anxiety disorders in the 1980s and in Alzheimer’s type of dementia in the 1990s. As decisions regarding the choice of treatment were to become based increasingly on findings in the clinical development of psychotropic drugs, psychiatric nosology was replaced by consensus-based classifications and psychopathology by rating scale variables used in the clinical studies conducted for the demonstration of therapeutic effects.
Introduction of consensus–based classifications, based primarily on Kraepelin’s (1899) nosology, created an impasse in resolving the heterogeneity within the diagnostic groups. Since these classifications were developed to reconcile widely different diagnostic formulations with the use of broad diagnostic categories they covered up component diagnoses. One such component diagnosis is “vital depression” -- a form of depression in Kurt Schneider’s (1920, 1950) clinical psychopathology that is characterized by “corporization,” “disturbance of vital balance” and the “feeling of loss of vitality”-- which allowed Roland Kuhn (1957) to discover imipramine’s antidepressant effect. This diagnosis is covered up to the extent that even in a severely ill patient who displays all the possible symptoms and signs considered for the DSM-IV-TM (American Psychiatric Association 1994) diagnosis of “major depression,” one still would not know whether the patient qualifies for “vital depression.” Another covered up diagnosis is “affect-laden paraphrenia” -- a form of “unsystematic schizophrenia” in Karl Leonhard’s (1957) classification of endogenous psychoses that is characterized by “paranoid delusions with affective loading and mood swings -- in which Frank Fish (1964) found that more than 4 in 5 patients responded favorably to antipsychotic phenothiazines.
The sensitive scales introduced for the demonstration of therapeutic effects compounded the problems with consensus-based classifications. Rating scales can be sensitized by the omission of psychopathological symptoms, relevant to psychiatric nosology, which are not influenced by treatment or by retaining only those items (variables) of a scale which show the largest changes. While the use of sensitive scales helps to demonstrate therapeutic effectiveness in the shortest possible time in the smallest number of patients, the omission of relevant psychopathological symptoms to psychiatric nosology precludes the possibility of finding by meta-analyses any relevant information for the identification of treatment-responsive forms of illness in the data collected in efficacy studies with psychotropic drugs. Since one of the essential prerequisites for the development of neuropsychopharmacology is the identification of a treatment responsive form of illness, consensus-based classifications and sensitized rating scales blocked the development of the combined discipline. By interfering with the development of neuropsychopharmacology they also precluded the possibility of using psychotropic drugs meaningfully in biological research in psychiatry.
American Psychiatric Association. Diagnostic and Statistical Manual-Third Edition, Washington: American Psychiatric Association; 1980.
American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition, Washington: American Psychiatric Association; 1994.
Angst J, Battegay R, Bente D, Berner P, Broeren W, Cornu F, Dick P, Engelmeier MP, Heimann H, Heinrich K, Helmchen H, Hippius H, Lukacs G, Pöldinger W, Schmidlin P, Schmitt W, Weis P. The documentation system of the Association for Methodology and Documentation in Psychiatry (AMP). Arzneim. Forsch. 1969; 19:399-405.
Asberg M, Perris C, Schalling D, Sedvall G. The CPRS-development and application of a psychiatric rating scale, Acta Psychiatr. Scand. 1978; Suppl.271:69.
Ban TA. They used to call it psychiatry, In: Healy, D. (Interviews), The Psychopharmacologists, London: Altman, an Imprint of Chapman and Hall; 1996, pp. 587-620.
Fish F. The influence of the tranquilizer on the Leonhard schizophrenic syndromes, Encephale 1964; 53:245-9.
Guy W. ECDEU Assessment Manual for Psychopharmacology – Publ. No. (ADM). (DHEW No. 76-338), Rockville: National Institute of Mental Health), United States Government Printing Office; 1976.
Guy W, Ban TA, editors. The AMDP-System. Manual for the Assessment and Documentation in Psychopathology. Berlin: Springer; 1982.
Kraepelin E. Psychiatrie. Ein Lehrbuch für Studierende und Ärzte, 7Auflage. Leipzig: Barth; 1899.
Kuhn R. Über die Behandlung depressives Zustande mit einem iminodibenzyl-derivat (G22355), Schweiz. Med. Wochenschr. 1957; 87:1135-40.
Leonhard K., Aufteilung der endogenen Psychosen, Berlin: Akademie-Verlag; 1957.
Macht DL. Contributions to psychopharmacology, Bull. Hopkins Hosp. 1920; 31:167-73.
Moreau de Tours J. Du Hachich et de L’Aliénation Mentale. Etudes Psychologiques, Paris: Fortin & Mason; 1845.
Scharfetter C. The AMP System, New York: Springer, New York; 1971.
Schneider K. Die Schichtung des emotionalen Lebens und der Aufbau der Depressionszustände, Z. Ges. Neurol. Psychiatr. 1920; 59:281-5.
Schneider K. Klinische Psychopathologie. 3. Auflage, Stuttgart: Tieme; 1950.
*Extracted from Thomas A. Ban: Academic Psychiatry and the Pharmaceutical Industry, published in Progress in Neuro-Psychopharmacology & Biological Psychiatry 2006; 30: 429-41.
July 16, 2020