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A comparative study of over 4000 case histories of patients admitted to the Kashchenko Moscow psychiatric hospital in 1951 and 1974 demonstrated that the character of natural history of schizophrenia under conditions of polypharmacotherapy has changed. The drug pathomorphosis was studied by comparing the clinical picture of the psychosis in the preneuroleptic period and under conditions of polypharmacotherapy. In polypharmacotherapy the ratio of the form of schizophrenia has changed towards an increase of attack-like forms and a drop in the number of cases with continuous forms of the disease. It was demonstrated as well that irrespective of the character of schizophrenia progress there was a considerable decrease in severe catatonic conditions, delusional excitation, pronounced stuporous states and increased proportion of depressions. Psychopathlike and pseudoneurotic symptoms during polypharmacotherapy did not undergo any serious changes.