Psychopharmacology and the Classification of Functional Psychoses 

By Thomas A. Ban and Bertalan Pethö


Four-Dimensional Classification


Concept of Psychosis

        Despite its extensive use, there is no generally accepted definition for the term "psychosis." In everyday psychiatric parlance it refers to mental illness of sufficient severity to produce conspicuously disordered behavior with lack of insight. This behavior cannot be understood as an extension or exaggeration of ordinary experiences (Leigh, Pare and Marks, 1972). While Jaspers (1913a, 1959, 1963) used the term in reference to disorders which "seize upon the individual as a whole," in the United States the term is employed primarily in referring to patients with hallucinatory experiences, delusional thinking and/or catatonic symptoms.

       Probably the most important contribution to the conceptual development of the term was made by Schneider (1959). He contended that the term "psychosis" should be used only to designate psychopathological manifestations which are the consequence of a disease process. This corresponds with Jaspers' (1963) notion that psychoses are "disease processes, regardless whether they are hereditary disorders beginning at certain times of life or called into being by exogenous lesions."

        The concept of psychosis put forward by Jaspers and Schneider was operationalized by Fish (1974). In Fish's definition the characteristic features of psychosis include lack of insight, distortion of the whole personality (by the illness), construction of a false environment (out of subjective experiences), gross disorder of basic drives (including that of self-preservation) and inability to make a reasonable social adjustment (Hamilton, 1974). In an alternative definition, put forward by Pethö, Ban, Kelemen et al. (1984), psychosis is a nonspecific syndrome characterized by lack of "insight" and psychopathological symptoms of sufficient severity to disrupt everyday functioning. The collapse of customary ways of social life may call for psychiatric hospitalization.

        By definition, excluded from psychotic disorders are "psychic deviations which do not wholly involve the individual" (Jaspers, 1963). Thus, excluded are patients whose personality is only in part affected, who can distinguish between their subjective experiences and reality, and who do not construct a false environment (Hamilton, 1974). Excluded also are personality disorders (i.e., variations of human existence which differ from the norm quantitatively rather than qualitatively) and neuroses (i.e., reactions of abnormal personalities to moderate or mild stress and reactions of normal personalities to severe stress) (Schneider, 1959).

       Psychosis is a diagnosis only within a one-dimensional model of classification, i.e., a classification which is based exclusively on cross-sectional (2nd developmental stage) assessment of psychopathology. Accepting psychosis as the end-point yields a one-dimensional treatment modality with an antipsychotic-neuroleptic drug. The underlying assumption is that the different forms of illness are only different stages of one and the same disease (psychosis) process and consequently can be controlled by one and the same (or pharmacologically similar) medication. This concept of "unitary psychosis" was first formulated by Neumann (1859).

        If the unitary hypothesis is valid, the psychopharmacological agents which come closest to fulfill therapeutic expectations are the chlorpromazine type of antipsychotic-neuroleptic drugs. Today there are at least 19 such antipsychotics, distributed among six different chemical classes available for clinical use in the United States and at least 12 more in other countries (See Appendix II, Table I). Most of these drugs are secondary or tertiary amines containing at least one aromatic ring linked to the amine position by an intermediate chain; and most of these drugs are active inhibitors of apomorphine-induced vomiting in dogs, apomorphine or amphetamine-induced stereotypic chewing and non-stereotypic agitation, and norepinephrine or epinephrine-induced mortality in rats. They also inhibit intracranial self-stimulation and conditioned operant behavior in all laboratory animals. At somewhat higher doses, traditional neuroleptics induce cataleptic immobility with a reduction of spontaneous motility and indifference towards the environment, and, at considerably higher doses, they induce ptosis, ataxia, prostration and other signs of CNS depression (Janssen, 1973).

        Antipsychotics share numerous common biochemical actions. They have a stabilizing effect on cell membrane, an inhibiting effect on the N-methyltransferase enzyme system and a decreasing effect on adenosine-triphosphate utilization. Since the early 1960s, however, most of the attention has been paid to the dopamine (DA) receptor blockade produced by these drugs. The original observation that antipsychotics increase the nialamide-induced accumulation of 3-0-methylated metabolites of DA and norepinephrine, i.e., 3-methoxytyramine and normetanephrine, was made by Carlsson and Lindquist as early as 1963. However, it was more than a decade later, employing X-ray crystallography (Creese, Burt and Snyder, 1975), before it was possible to demonstrate that DA receptor blockade actually takes place. Furthermore, by employing radioligand-binding techniques, it was revealed that clinical potencies, based on a mg/kg basis of neuroleptics correlate well with the binding affinities at D2 receptors, i.e., receptors which can be selectively labelled with 3H-haloperidol and 3H-spiroperidol (Kebabian and Calne, 1979). In addition, there is some evidence that neuroleptics also have opiate receptor binding properties (Jacquet and Marks, 1976).

        The most consistent finding following chronic (1 to 3 weeks) antipsychotic administration is D2 receptor blockade and a consequent increase in the number, with a decrease in the affinity, of these receptors in the striatum and mesolimbic areas (Burt, Creese and Snyder, 1977; Muller and Seeman, 1977, 1978; Theodorou et al., 1981). Therefore, one may hypothesize that the biochemical substrate of psychosis is in the DA structures of the limbic lobe. At variance with this contention, however, are findings in clinical psychopharmacological studies which suggest that there is a differential therapeutic response in psychotic patients to antipsychotic drugs. Although antipsychotics undoubtedly are the most effective treatment for psychoses, some psychotic patients remain refractory to antipsychotics and require other treatment modalities for control. Since a differential therapeutic response indicates biological heterogeneity, the findings of a differential therapeutic response is in line with the contention that psychosis consists of more than one diagnostic groups.