Ladislas J. Meduna

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Ladislas Joseph Meduna (1896-1964) was a Hungarian neurologist who discovered the first effective drugs for the treatment of schizophrenia.

Meduna was born to a well-to-do family in Budapest, Hungary, in 1896. He studied medicine in Budapest from 1914 to 1921, his studies being interrupted by military service in the Italian front from 1915 to 1918, during the First World War.

He was interested in pursuing medical research in neurology, and soon got an appointment to the Hungarian Interacademic Institute for Brain Research, also in Budapest. There, he researched the structure and development of the pineal gland and of microglia, the neuropathology of lead poisoning, avitaminosis, and several other subjects. In 1927 he moved to the Psychiatric Institute and began clinical and research work in psychopathology.

Meduna's interest in treating schizophrenia with somatic (shock) therapies began with his work on the apparent antagonism between this disease and epilepsy. He found that 16,5% of epileptic patients who developed psychotic symptoms had a remission of epilepsy. The reverse association also seemed true: of more than 6,000 patients with schizophrenia, only 20 had had epilepsy. There were anedoctal reports of cures of schizophrenia in patients who developed epileptic seizures.

Meduna had then the idea that seizures could be used to treat schizophrenia. He tried several pharmacological agents to safely induce convulsions, such as the alkaloids strychnine, thebaine, coramin, caffeine, and brucin. Finally, he discovered that camphor dissolved in oil was effective in animals as well as in humans. In order to experiment treatment in real patients without putting his career at risk, however, Meduna had to use another psychiatric hospital, at Lipotmezö, outside Budapest. On January 23, 1934, he tried the injection of camphor oil in a severe 33-year-old catatonic patient. After just 5 treatments, catatonia and psychotic symptoms were abolished. Increasing his casuistics to 26 patients, Meduna achieved recovery in 10 of them and improvement in 3 more (in other words, a 50% positive results).

Soon, Meduna discovered pentylenetetrazol, or metrazol (brand name Cardiazol), a powerful convulsant agent, as being more effective and quick-acting than camphor, and started using it in intramuscular and intravenous injections.

He published his results in 1935 and his results quickly provoked a commotion in psychiatry around the world, because schizophrenia was then considered a hereditary and incurable condition. In 1939, he published in German a monograph titled Die Konvulsionstherapie der Schizophrenie, describing his results with 110 patients. He reported an astounding 95% remission rate in acute schizophrenic patients, and of 80% in patients with less than one year duration of the disease. Longer durations of disease had increasingly smaller effectiveness of metrazol therapy. His results were reproduced in many other centers around the world and this form of therapy became commonplace, despite its harsh collateral effects. Meduna's work influenced the discovery of a more stable, less detrimental and more effective form of convulsive therapy, by means of electroconvulsive therapy, which was discovered by Italian researchers Ugo Cerletti and Lucio Bini, in Rome. Metrazol convulsive therapy was afterwards abandoned.

Meduna also developed carbon dioxide therapy. The patient had to breathe a mixture of 30% carbon dioxide and 70% oxygen until becoming unconscious, the treatment being repeated several times weekly. Although it was effective in relieving obsessive-compulsive disorders, it was not so effective as convulsive therapy, and it was abandoned.

With the increase of anti-semitism and the rise to power of National Socialism, Meduna emigrated to the USA in the following year (1938), to become Professor of Neurology at Loyola University, in Chicago. One of his last contributions to psychiatry was the study of confusional and dream-like states in psychoses (oneirophrenia). After the war, he moved his research to the Illinois Psychiatric Institute, where he worked until his death in 1964.

[edit] References

Fink M. - Meduna and the Origins of Convulsive Therapy. Am. J. Psychiatry, 141(9): 1034-1041, 1984. correction, 141:1648
Fink, M: ECT: Serendipity or Logical Outcome? Psychiatric Times January 2004 Vol. XXI Issue 1
Mackay RP. Ladislas Joseph Meduna 1896-1964. Recent Adv Biol Psychiatry. 1965;8:357-8 [Medline citation]
Fink, M: Historical Article: Autobiography of L.J. Meduna. Convuls Ther 1985; 1:43–57; 121–135 [Medline citation]
Meduna LJ: Die Konvulsionstherapie der Schizophrenie. Halle, Germany, Carl Marhold, 1937
Fink, M: Ladislas J. Meduna, M.D. 1896–1964. Am J Psychiatry 156:1807, November 1999
The Papers of Ladislas J. Meduna (1896-1964). University of Illinois Archives Holdings.