Thomas A. Ban
Neuropsychopharmacology in Historical Perspective

Psychopharmacology and the Classification of Functional Psychoses

3. Classification of Mental Disorders and Psychopharmacology – ICD-9 and DSM-III

       The practical need for developing a new system of classifying “functional psychoses” is closely linked to progress in psychopharmacology. It was in part in response to this need that the two most extensively employed diagnostic classifications, the ninth edition of the International Classification of Diseases (ICD-9) of the World Health Organization (WHO) and the third edition of the Diagnostic and Statistical Manual (DSM-III)  of the American Psychiatric Association (APA), were introduced (APA 1980; WHO 1967).

Psychopharmacology

       Arguably the psychopharmacological era began on January 19, 1952 when chlorpromazine was given for the first time   to  a  psychiatric  patient  by  Hamon, Paraire and Velluz (1952) at Val-de-Grace, the famed military hospital in Paris (Ban 1972). From Val-de-Grace, chlorpromazine raced through the mental hospitals of France within the single year of 1952 (Delay and Deniker 1952), transforming disturbed wards, reforming therapy and remodeling research (Caldwell 1970). Swiss psychiatrists began to use chlorpromazine in January 1953 (Staehelin and Kielholz 1953) and by the Spring of 1953 the psychopharmacological “revolution” was well underway throughout continen­tal Europe. Lehmann and Hanrahan's (1954) paper, the first American publi­cation on chlorpromazine, appeared in February 1954 in the American Medical Association's Archives of Neurology & Psychiatry; and  one year later the first Australian (Webb 1955) and Russian (Tarasov 1955) publications were also in print.

       As chlorpromazine was introduced at a time when interest in psychiatric diagnosis was dormant, the first publications reported on therapeutic effects with the drug on
“psychic disturbances” (psychischen storungen) in general and in “psychotic” patients (cas de psychoses) in particular (Delay and Deniker 1952; Staehelin and Kielholz 1953). In the first Ameri­can publication (Lehmann and Hanrahan 1954), chlorpromazine was labelled as a "new inhibiting agent for psychomotor excitement and manic states” and subsequent articles suggested that chlorpromazine is an “antipsychotic” agent which can control psychoses regardless whether “organic” or “functional.” In fact, it was not until the 1960s that it was recognized that “antipsychotics” are particularly useful therapeutic agents in the treatment of "functional psychoses" and  have  an  especially  favorable  action  in  the  “schizophrenias” (Casey, Bennett, Lindly et al. 1960; NIMH Collaborative Studies 1964).

       The phenothiazine nucleus, the basic constituent of chlorpromazine, was first synthesized in 1883 by Bernthsen. It consists of two benzol rings attached to each other by a sulfur atom and a nitrogen atom. A structurally similar nucleus, the iminodibenzyl nucleus, the basic constituent of imipramine, the first tricyclic antidepressant, was described 16 years later by Thiele and Holzinger (1899). In the course of the search to find “chlorpromazine-like” compounds to treat “psychosis” and especially “schizophrenia,” imipramine was chosen to be studied. It failed to show “antipsychotic” properties but Kuhn (1957) recognized its therapeutic potential in “depression” in patients with a “vital depressive predisposition.” The antidepres­sant effects of imipramine received additional substantiation within a year from Kielholz and Battegay (1958) in Europe and from Lehmann, Cahn and deVerteuil (1958) in North America. However, it was not until the mid-1960s, i.e., approximately eight years later, that the “antidepressant” effects of imipramine were established with reasonable certainty (Ban 1974, 1981). By pooling data from 23 published reports which included 550 patients treated with imipramine and 459 with placebo, Klerman and Cole (1965) showed that the overall improvement rate was significantly higher with imipramine (65%) than with an inactive substance (35%). Similar findings were obtained about five years later by Angst (1970).

       Lack of interest in psychiatric diagnosis made it even more difficult to recognize the mood stabilizing effect of lithium salts. As early as 1949 Cade reported on the successful treatment of 10 manic patients with lithium and noted that the first patient relapsed when treatment with lithium was stopped. However, it was not  before  the  1970s,  i.e., more  than  20 years later, that the  therapeutic  effects  of  lithium  salts  were  proven beyond reasonable doubt in manic depressive patients during the acute, maintenance and prophylactic phases of treatment (Jefferson and Greist 1977).

       Chlorpromazine, imipramine and lithium have brought about fundamental changes in the treatment of "functional psychoses." In view of this, and in-spite of all the acknowledged limitations of these “psychotropic” agents, the treatment of choice for functional psychoses today is pharmacotherapy with antipsychotics, antidepressants and mood stabilizing lithium salts.

       There is substantial evidence that no other therapeutic procedure can compete with these treatments in terms of rapidity of effectiveness, sustained action, general availability and ease of application. These practical advantages have provided an incentive to develop a large number of antipsychotic and antidepressant drugs.

       The  large   number  of   available  “antipsychotics”  (also referred to as “neuroleptics”)  were  listed in a report, based on a multi-national survey, carried out in 768 chronic hospitalized schizophrenic patients in eight countries during the early 1980s. Findings revealed that 739 or 96.2% of the 768 patients were treated with one or more of 31 different neuroleptics (Ban, Guy and Wilson 1984b). No similar figures are available for antidepressants. Yet, by 1981, at least 10 structurally different groups of “tricyclic” and 10 other structurally different groups of “non-tricyclic” antidepressants were in clinical use and/or employed in clinical investigations. The 10 groups of tricyclic antidepressants include the dibenzazepines, dibenzodiazepines, dibenzocycloheptadiens, dibenzocyloheptatriens, dibenzothiepines, dibenzoxe­pines, dibenzoxazepines, anttracenes, anthridines and acridans; and the 10 groups of non-tricyclics include the dibenzobicyclo-octadienes, carboxylic acid esters, amides and amidoximes, arylalkyl and arylcycloalkylamines, phenoxyalkylamines, diaryl and diaryloxy-derivatives, arylbicyclic compounds, oxazoles, imidazoles and triazoles, benzpyrazoles and benzididazoles, con­densed indoles and quinolines and tetrahydroisoquinolines (Ban 1981). Demonstration of therapeutic efficacy or possible differential activity of these drugs requires sensitive instru­ments for the assessment of change.

       Another important factor in the renewed interest in the diagnosis and classification of psychiatric disorders in general and “functional psychoses” in-particular is related to the recognition of the biological nature of these conditions. As psychopharmacological agents may promptly reverse psychopathological symptoms and their continued administration may maintain patients in remission it is increasingly recognized that “psychodynamic theories” cannot offer a meaningful under­standing about the nature of these conditions. On the other hand, detection of psychopathological symptoms may bring to attention distinct psychopathological structures which are affected by the disease. Similarly, understanding the action mechanism of drugs with specific therapeutic effec­tiveness in a distinct disorder and with equal therapeutic effectiveness during the different developmental stages of the disorder, may lead to the identification of functional alterations of the morphological substrate(s) responsible for the clinical manifestations. One of the essential prere­quisites of such research is the delineation of pharmacologically homogeneous,  valid diagnostic groups.

ICD-9 of the World Health Organization

       By the time the changes brought about by the introduction of “psychotropic drugs “were recognized  experts from 35 countries participated in a World Health Organization program on the standardization of psychiatric diagnosis, classification and statistics. Their review of the state-of-affairs resulted in the “glossary” of mental disorders, which was distributed as a companion to the eighth edition of the International Classification of Diseases (ICD-8) (WHO 1967).  The same glossary, with some modification, was incor­porated in Chapter V of the ninth edition of the lCD (ICD-9) completed in 1975 and published in 1977 (Jablensky, Sartorius, Hirschfeld and Pardes 1983; WHO 1977).

       The mental disorders section of ICD-9 is primarily directed to ful­fill the needs of epidemiological research and is firmly rooted in a tradi­tional framework of psychiatric classification. It is based on the separa­tion of “psychoses” from “neuroses” and on the dichotomy between organic psychotic conditions and other psychoses. Disorders subsumed under "other psychoses" in the ICD-9 are commonly referred to as “functional psychoses,” implying the absence of structural changes.  

       Functional psychoses in the ICD-9 are divided into three “endogenous” and one “reactive” group of disorders. (It should be noted, however, that the terms “functional,” "endogenous" and “reactive” are not used in the ICD-9.) The three “endogenous” groups of disorders are “schizophrenic” psy­choses (including acute schizophrenic episode; latent and residual schizophrenia; and simple, hebephrenic, catatonic, paranoid and schizo­affective types of schizophrenia); “affective psychoses” (including manic­ depressive psychosis manic, depressed and circular types); and “paranoid states” (including paranoia, paraphrenia, induced psychosis and paranoid state simple type). The reactive group, referred to as other nonorganic psychoses, includes reactive confusion, acute paranoid reaction, psychogenic paranoid psychosis and other nonorganic psychosis depressive and excitative types.

       To up-date the ICD-9, a major “International Conference on Diagnosis and Classification” was convened in Copenhagen in 1982. Participants in this conference agreed that among the factors contributing to the revival of interest in psychiatric diagnosis were the advances in pharmacological treat­ment which required more refined diagnostic assessment and the advances of biological research towards an understanding of the causal mechanisms underlying some of the major mental disorders. Other contributing factors con­sidered were the attractions of new tools, such as standardized instruments for diagnostic interviewing, operationalized diagnostic criteria and experiments with multi-axial recording systems.

       No consensus was reached at the Copenhagen conference regarding a theory underlying the classification of mental disorders. Some participants expressed the view that disease entities in psychiatry are not intrinsically different from disease entities in general medicine with specific causes, symptoms, course, outcome (corresponding with the original contention of nosological theory) and response to treatment. At the same time, other participants maintained that the phenomenology of mental disorders seems to reflect etiologically non-specific responses of the personality to neuro­chemical events or altered cerebral structures. However, there was a widely shared contention that distinctions like those between "organic" and "func­tional," or "endogenous" and "exogenous," or "psychosis" and “neurosis,” were at least questionable and needed revision or at least qualification (Jablensky, Sartorius, Hirschfeld and Pardes 1983).

       Regarding "functional  psychoses," it was agreed that the designation of these disorders as such  is  misleading  because  "organic"  features  might  be present in presumably "functional conditions"  and  because  many  of  the syndromes within this category do not exhibit the features corresponding to  the  traditional notion of "psychosis." The participants agreed that the extensive clinical and genetic “evidence” for schizophrenia made it a valid and useful concept. It is a disorder, or a group of disorders, for which a predisposition is genetically transmitted, and which is of worldwide occurrence. The same applies to manic and depressive illnesses. There is both clinical and genetic “evidence” for a distinction between unipolar and bipolar affective disorders. It was also agreed that there are good reasons to classify patients with "schizoaffective"  symptoms   separately from both the schizophrenic and the affective categories. There are acute psychoses of brief duration which do  not  belong  to  either  the  schizophrenic or the affective diagnostic group and there are a variety of paranoid and other delusional states which tend to occur with a peak frequency in middle or late middle age (Jablensky, Sartorius, Hirschfeld and Pardes 1983).

       As a follow up to the Copenhagen Conference, the Division of Mental Health of WHO held an informal consultation at which proposals for the classification of mental disorders and psychosocial factors in the ICD-10 were discussed. The ICD-10 is planned to be completed by 1990 and implemented in 1992 or 1993. If the present outline is accepted, the conditions traditionally subsumed under "functional psychoses" wi1l be included under the headings of schizophrenic and related disorders and mood (affective) dis­orders. Subsumed under the heading of schizophrenic and related disorders will be schizophrenia (paranoid, hebephrenic, catatonic, undifferentiated and residual and post-schizophrenic depression); schizophrenic spectrum disorders (schizotypal personality disorder and simple schizophrenia); persistent delu­sional disorders (paranoia and monosymptomatic, induced and other persistent delusional disorders); acute and transient psychotic disorders (acute delusional episode, cycloid psychosis, psychogenic delusional disorder: acute dissocia­tive-confusional episode, acute schizophreniform episode and other acute psychotic disorder); and other non-organic psychotic disorders. Subsumed under the head­ing of mood (affective) disorders will be bipolar affective disorder (currently manic, depressive, mixed or in remission); recurrent depressive disorder (severe and mild); depressive episode (severe and mild); other affective disorder; schizo­affective disorder (schizomanic and schizodepressive); and chronic affective states (cyclothymia and dysthymia) (WHO 1984).          

DSM-III of the American Psychiatric Association

       In contradistinction to the ICD-9, and more in keeping with the goals of ICD-10, the Third Edition of the Diagnostic and Statistical Manual of Mental Disorders  (DSM-III)   of  the  American  Psychiatric  Association  is  oriented  to  fulfill   the  need created by research in psychopharmacology and necessary for progress in the field. It is a multi-axial system of evaluation (Axis  I – Clinical  Syndromes,  Axis  II – Per­sonality Disorders,  Axis III – Physical Disorders,  Axis IV – Psychosocial Stressors and Axis V – Highest Level of Adaptive Functioning) which is based  on operationally defined criteria.

       Preparation of the DSM-III by a “Task Force on Nomenclature and Statistics” of the American Psychiatric Association (APA) began in 1976. It was completed and approved at the 1979 Annual Meeting of the APA and published in 1980.

       In DSM-III each mental disorder is characterized by a clinically signi­ficant behavioral or psychological syndrome   which is associated with either a painful symptom or impairment in one or more important areas of function­ing. DSM-III diagnoses imply behavioral, “psychological” and/or biological dysfunction. DSM-III is not a classification of patients but a classification of disorders. It deals with illnesses and not with disturbances in the relationship between the person and society.

       The  origin  of  the DSM-III  can be traced  to DSM-I,  published in 1952.DSM-I,  the  first  edition  of  the  Manual, was  firmly  rooted  in Adolf  Meyer's  (1917, 1934)  psychobiological  view that mental disorders  represent reactions of the personality to psychological, social and/or  biological factors. By the time the second edition, DSM-II, went into effect in 1968, the classification was brought in line with the eighth edition of the ICD of the WHO. The term "reaction" was no longer used, and the terms used by and large did not imply a particular theoretical framework for under­standing nonorganic mental disorders. Subsequently, however, there was a divergence between the ICD and the DSM. Thus, for example, the traditional separation between psychosis and neurosis present in ICD-9 was eliminated and both terms were replaced by the single term "disorder” in the DSM-III.

       In the DSM-III disorders traditionally subsumed under functional psy­choses are grouped under four major headings: schizophrenic disorders, paranoid disorders, psychotic disorders not elsewhere classified and affective disorders. Five types of schizophrenic disorders are differentiated:  disorganized, catatonic, paranoid, undifferentiated and residual; four types of paranoid disorders: paranoia, shared paranoid disorder, acute paranoid disorder and atypical paranoid disorder; three types of psychotic disorders not elsewhere classified: brief reactive  psychosis, schizoaffective disorder and atypical psychosis; and four types of affective dis­order:  bipolar disorder, major depression, cyclothymic disorder and atypical depression. In schizophrenic disorders consideration is also given to the course of the illness and each of the different types are identified as sub-chronic, chronic; sub-chronic with acute exacerbation; chronic with acute exacerbation and in remission. Similarly, the diagnosis of major depressive episode is further qualified whether it displays psychotic (mood-congruent or mood incongruent) and/or melancholic features or is in remission.

       The DSM-III represents a major attempt to integrate psychiatry with the other medical disciplines. Yet, Canadian critics of DSM-III contend that the quest for reliability, operational rigor and completeness has overshadowed con­cern for validity, clinical flavor and psychodynamic understanding. The same critics argue that dismissal of psychodynamic formulations and neglect of humanistic approaches to complex and ambiguous realities reflect an arid view of psychiatric diagnosis. According to one of these critics, "DSM-III is like a bikini — it shows you everything but the essentials." According to another critic, “DSM-III is a gigantic defense against diagnostic problems in psychiatry.” The same Canadian critics disagree with the elimination of terms, such as “psychotic,” “neurotic” and "psychopathic," as well as the abandonment of the exogenous/endogenous and neurotic/psychotic polarities.      They argue that despite the problematic nature of these dichotomies, these distinctions are important and are not adequately repre­sented in DSM-III.

       The diagnoses of “paranoid” disorders and “schizophreniform” disorders in DSM-III were faulted for their almost total neglect of the European literature and consequently for relying heavily on the duration criterion in differential diagnosis (Engels, Ghadirian and Dongier 1985). Despite all critical comments the Canadian survey revealed that 90% of the 99 respondents (university-based psychiatrists) used Axis I diagnosis in their undergraduate (94%) and postgraduate (99%) teaching and research (98%). Thus, the results of the survey corroborated the main find­ings of a former Canadian survey carried out by Junek (1983) who reported that the majority of his respondents considered DSM-III as the diagnostic system of the future.

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April 22, 2021