Zur Frage der therapeutischen Wirksamkeit eines Neuroleptikums bei chronisch Schizophrenen mit Dosierungen oberhalb und unterhalb der "neuroleptischen Schwelle"
Between January 25 and June 10, 1968, the neuroleptic pimozide was tested in a group of 24 female chronic schizophrenics, comparing the effects of doses below the neuroleptic threshold with that of those above. Criteria used for the study were the standard schema for the investigation of neuroleptics and the continuous testing of fine motor performance developed by Haase and the questionnaires prepared by the pharmaceutical company of Janssen GmbH. On oral administration, pimozide is to be included among the most potent neuroleptics, with a threshold dose of 6 mg daily. A single daily dose of the drug sufficed. With doses from 1.5 up to 24 mg daily, all patients showed fine motor signs of extrapyramidal hypokinesia in the hand-writing test. This range of up to 16fold difference in the threshold for strongly and weakly disposed individuals conforms to our previous experience with other neuroleptics. The maintenance dose, i.e. the dose achieving the maximum of antipsychotic effect for the minimum of coarse motor extrapyramidal symptoms, was well above the threshold dose. Coarse motor extrapyramidal phenomena were observed in about 50 % of the cases. The incidence of dyskinesia was no less than usual with neuroleptics (4 patients). These phenomena affected the head and the lower extremities. The major purpose of the investigation was to compare the effects of doses below the threshold with those above. The neuroleptic threshold dose is that which in the hand-writing test suffices to provoke fine motor signs of extrapyramidal hypokinesia. Below the threshold dose, improvement of affect was observed in 20 out of 24 patients, i.e. they became somewhat more accessible to contact and to occupational therapy. One patient showed no change, and three became worse emotionally. Hallucinations became less frequent or severe in five patients. The most marked therapeutic success was obtained with doses above the neuroleptic threshold. In six cases, there was evident im provement in the hallucinatory experience, and three were completely free from hallucinations for the first time in several months. In ten cases there was decided improvement in paranoid delusions, with complete disappearance for the first time in months in four. In two cases, the condition deteriorated. Of 18 patients subsequently transferred to half the threshold dose, 13 deteriorated again within four weeks, three of them in the first week, five in the second and two in the third. Three patients (Nos. 1, 16, 19) presented increased hallucinations, three others (Nos. 7, 21, 22) increased delusions and another four (Nos. 4, 8, 20, 24) both hallucinations and paranoid delusions. In one case, psychomotor deterioration with mutism and stupor predominated. One patient became severely depressive and increasingly paranoid. Altogether, only five patients tolerated this trial reduction without deterioration. This served to confirm once again that the main antipsychotic effect of neuroleptics is obtained with doses lying above the neuroleptic threshold. In this context, the term antipsychotic refers to the influence on psychotic experience (paranoid delusions, hallucinations, etc.) as well as on the pronounced emotional excitation and tension of psychotic origin, with the resulting behavioural problems.