Convulsive Therapy: Chemical

   (METRAZOL)

   (1934)

   Budapest neuropathologist Ladislaus von Meduna (1896–1964) introduced the modern practice of convulsive therapy by chemical means. Meduna, a graduate of the Semmelweis Medical University in 1922, had trained as a neuropathologist at the Budapest Interacademic Institute for Neurological Research, then in 1926 followed his chief Prof. Károly Schaffer (1864–1939)—who educated an entire generation of Hungarian psychiatrists in histology (the equivalent of biochemistry today)—to the university department of psychiatry; Meduna was also a ward chief at the state asylum at Budapest-Lipótmezö. Meduna had noticed under the microscope that glia cells (the connective tissue of the brain) in schizophrenic patients looked quite different from those in epilepsy patients, and because epilepsy and schizophrenia rarely occurred in the same patient, Meduna hypothesized a kind of opposition between the two illnesses. It followed, he thought, that if epileptiform fits could be induced in schizophrenics, it might ameliorate the disease. He began by using camphor as the epileptogenic drug. (There had been previous attempts in medicine to induce fits with camphor, although these were unknown to Meduna at the time.) Shortly thereafter, Meduna switched to the more soluble and faster-acting pentylenetetrazol as the convulsion-inducing drug, which had been marketed as a mild cerebral and cardiac stimulant under the brand names Cardiazol in Europe and Metrazol in the United States.

   In 1935, in the Journal of Combined Psychiatry and Neurology (Zeitschrift für die gesamte Neurologie und Psychiatrie), he reported on the first 26 patients, some of whom had received camphor, others Cardiazol. Of the 26, 10 experienced substantial improvement; this was at the time when the therapeutics of schizophrenia were virtually nonexistent. In 1937, he provided a comprehensive view of his treatment in The Convulsive Therapy of Schizophrenia (Die Konvulsionstherapie der Schizophrenie). Meduna’s treatment was soon overtaken by electroconvulsive therapy (ECT) because the latter was easier to use, better tolerated by the patients, and had equal efficacy. Also, outpatients often disliked Metrazol therapy because of the problem of delayed convulsions: They would return home and experience yet another convulsion there. Yet, Cardiazol (Metrazol) is important as the first of the convulsive therapies. Meduna emigrated to the United States in 1939, becoming professor of psychiatry first at Loyola University, then at the University of Illinois medical school, both of which are in Chicago. In Chicago, he occupied himself with the understanding of oneirephrenia, a form of schizophrenia characterized by clouding of consciousness (see his monograph in 1950; see also Willi Mayer-Gross’s 1924 monograph); he also became involved with the possible carbon-dioxide treatment of neurosis, writing a monograph on the subject in 1955; it was a method that failed to catch on. First to report on Metrazol in the United States was Hungarian-born psychiatrist Emerick Friedman (1910–?), who read a paper on it at a staff conference of the Buffalo City Hospital in May 1937.