Psychopharmacology and the Classification of Functional Psychoses
By Thomas A. Ban and Bertalan Petho
Classification and Clinical Psychopharmacology
Psychopharmacology
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 and Psychiatry; and one year later, the first Australian (Webb, 1955) and Russian (Tarasov, 1955) publications were also in print.
Because 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 whether organic or functional. In fact, it was not until the 1960's, 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 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, was described 16 years later by Thiele and Holzinger (1899) (Figure 2). In the course of a 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. 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 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 ten manic patients with lithium and noted that the first patient relapsed when lithium treatment 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/or mood stabilizing lithium salts. There is substantial evidence that no other single 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 sufficient incentive to develop a large number of antipsychotic and antidepressant drugs (and also a number of different brands of lithium salts).
The large number of available antipsychotics (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 percent of the 768 patients were treated with one or more of 31 different neuroleptics (Ban, Guy and Wilson, 1984b) (see Appendix II, Table II). No similar figures are available for antidepressants. By 1981, however, at least ten structurally different groups of tricyclic and ten other structurally different groups of non-tricyclic antidepressants were in clinical use and/or employed in clinical investigations. The ten groups of tricyclic antidepressants include the dibenzazepines, dibenzodiazepines, dibenzocycloheptadiens, dibenzocyloheptatriens, dibenzothiepines, dibenzoxepines, dibenzoxazepines, anthracenes, anthridines, and acridans; and the ten 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) (see Appendix II, Tables III and IV). Demonstration of therapeutic efficacy or possible differential activity of these drugs requires sensitive instruments for the assessment of change. Identification of therapeutically responsive patients and differentiation of these patients from the treatment refractory ones require valid diagnostic groups within the functional psychoses.
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. Because psychopharmacological agents may promptly reverse psychopathological symptoms and their continued administration may maintain patients in remission or even have a prophylactic effect, it is increasingly recognized that "psychodynamic theories," cannot offer a meaningful understanding about the nature of these conditions. On the other hand, description of the form 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 valid diagnostic groups.
May 30, 2024