This year marks the 70th anniversary of the first use of induced seizures to treat mental disorders. Read about the career of Ladislas Meduna, M.D., the Hungarian neuropathologist who pioneered this treatment method. Although his theory that convulsive therapy is effective because it increases glial cell function was disproved, it remains one of the
(The first use of induced seizures to treat a mental disorder was 70 years ago. In a series of columns, the implications of this anniversary will be explored--Ed.)
On Jan. 23, 1934, the Hungarian neuropathologist Ladislas Meduna, M.D., injected camphor-in-oil in a catatonic patient, seeking to relieve schizophrenia. The patient seized and survived. Following the model of fever therapy for neurosyphilis--a treatment that was then in high regard and wide demand--Meduna repeated the injections at three- to four-day intervals. After the fifth injection, the patient became alert and talkative, and, after two additional seizures, he was no longer psychotic or catatonic. Despite an illness of four years duration, he returned to his home and to work; at five-year follow-up he remained well. Meduna repeated the experiment in nine additional patients, reporting success in seven in his first report in 1935.
Convulsive therapy for schizophrenia was rapidly adopted throughout the world. Its benefits in depression and mania were quickly recognized as it became the main treatment of the severe psychiatrically ill. For a while it was replaced by medications that were deemed as effective, less expensive and more easily prescribed, but when the limits of the medications were realized, interest in convulsive therapy re-awakened.
The bizarre nature of inducing a seizure encouraged its stigmatization. Electroconvulsive therapy became the target of a vocal antipsychiatry movement that obtained legislative restrictions to its use. Our lack of understanding of a mechanism by which grand mal epileptic seizures could improve disordered behavior led to the belief that convulsive therapy had no scientific basis, justifying its disregard.
How did Meduna develop the notion that seizures might relieve a lifelong mental illness? How did he overcome the widespread fear of epileptic seizures so as to induce them in a human being?
Meduna was born in 1896 and, after a rigorous Catholic education, began his medical studies in Budapest, Hungary, in 1914. Anticipating a call to military service, he volunteered for the artillery, serving in the Italian front from 1915 until the war's end. After delays occasioned by postwar Communist insurrections, Meduna completed his medical studies in 1921. A year later, he was appointed to the research faculty at the Hungarian Interacademic Institute for Brain Research in Budapest.
His first report describing the structure and development of the pineal gland was followed by reports on the neuropathology of avitaminosis, lead poisoning, and the structure and concentration of microglia. In 1927, he moved to the Psychiatric Institute where he cared for hospitalized psychotic patients and learned a new language of psychopathology. Meduna described a heartbreaking work schedule with little possibility to offer relief for his patients.
Meduna had reported that an increased glial reaction followed head trauma. An effusive glial increase was also seen in patients with epilepsy, but no such reaction was measured in those with schizophrenia. Was the glial increase a response to the seizure or secondary to aging and systemic illness? Meduna identified six patients with focal seizures in whom the brain focus was surgically excised. These tissues showed an increased proliferation of glia. Meduna hypothesized, "There was almost complete abolition of the function of the glia cells in schizophrenia and an increased proliferation in epilepsy."
He screened the literature for evidence of similar antagonism. When schizophrenia was complicated by epilepsy, the epileptic attacks either became infrequent or disappeared. While 1% of patients with epilepsy admitted to the state hospital improved, 16.5% of those who developed acute psychoses remitted. Seeking to test whether the disorders could influence one another, Professor Nyir", a fellow Hungarian, had injected the blood of patients with schizophrenia into those with epilepsy, to no avail. In another report of 6,000 patients with schizophrenia, only 20 had epileptic attacks before or during their illness. In two clinical reports, the psychosis of patients with schizophrenia cleared when they developed epileptic attacks.
These experiences encouraged Meduna to explore seizures as an antidote for schizophrenia. His first hurdle was to devise a safe and effective method of seizure induction. He needed a nonpoisonous substance that would safely produce epileptic attacks. He tested strychnine, thebaine, coramin, caffeine, brucin, absinthe and, finally, camphor dissolved in oil seemed to best meet his needs. He determined the convulsive and lethal doses of subcutaneous injections in guinea pigs and examined the pathology in animals sacrificed after extensive seizures.
The next hurdle was the selection of an experimental subject. At the Psychiatric Institute, schizophrenia was viewed as an immutable, inherited disorder and efforts toward a cure were considered quackery. Meduna joined the staff at the chronic psychiatric hospital at Lipotmez", outside Budapest. For the first experiment, he selected a psychotic man with catatonic schizophrenia who had required intensive nursing care for four years and had little likelihood of recovery.
The patient did survive the seizures, and they did relieve his illness. Meduna undertook additional experiments in other patients who were as severely ill. One remission followed another. He soon substituted intravenous cardiozol (Metrazol) for camphor and, in 1935, he published his first report: "An attempt to influence the course of schizophrenia by biologic means."
Similar experiments were stimulated throughout the world. By May 1937, many authors confirmed Meduna's findings at an international meeting in Berne, Switzerland. At this meeting, Lucio Bini of Rome described animal experiments to substitute electrical stimulation for chemicals. A successful patient demonstration in Rome in May 1938 showed this technique to be easier to use and as effective.
Electroconvulsive therapy was quickly established as the dominant treatment of the severe psychiatrically ill. Its widespread use changed the culture of hopelessness and fear that marked the institutions that cared for these patients.
Meduna described his experience with 110 patients in his 1937 monograph: Die Konvulsionstherapie der Schizophrenie. The remission rate varied with the type and duration of the illness. For those ill for less than a year, more than 80% remitted. The remission rate fell to 50% for those ill from one to two years; 25% for illnesses of three to five years; and there were no remissions in those with illnesses longer than a decade. Of patients with the acute form of schizophrenia, 95% remitted. Of those with "process schizophrenia," 57% remitted, but if the illness was allowed to go untreated into "post-process" schizophrenia, only 6% remitted. While our diagnostic language and criteria no longer recognize these criteria, the experience with ECT today confirms Meduna's conclusions that patients with schizophrenia treated during the first two years of their illness--when the psychosis is dominated by positive symptoms--have an excellent prognosis for sustained remission. For those patients in whom the illness has been allowed to fester for years--and especially for those who develop the negative symptoms of apathy, withdrawal and emotional blunting--relief is no better than with other treatments.
How are we to assess Meduna's contribution? Of the many biological treatments introduced into psychiatry in the first half of the 20th century--prolonged sleep, insulin coma, lobotomy and subconvulsive electrostimulation--only ECT remains in wide use. The indications have been broadened and the treatments made safer by sedation and muscle paralysis. Electroconvulsive therapy is no longer limited to acute forms of schizophrenia; it is widely used in patients with major depression, mania and catatonia. It is more effective than alternative treatments for these conditions, yet its use is severely stigmatized and widely considered as the last resort, after all other treatments have failed. Such an attitude dooms many patients to lifelong illness; family turmoil; poverty; despair; loss of self-esteem; and revolving residence between hospital, prison, group homes and periods of homelessness.
Meduna's hypothesis is spurned. The antagonism hypothesis is assumed to have been disproved or founded on fantasy, but no experiment has challenged it. Inducing seizures in patients who are psychiatrically ill yields remarkable benefits that are achieved quickly and at little cost. While the basis in a glial reaction is not demonstrated, the accompanying changes in brain chemistry warrant much greater attention. The lesson of the clinical benefits of induced seizures is ignored by academia, by government research policy and by the medical industrial establishment. Such disregard is shameful and wasteful. For more than half a century, we have seen the development of no new treatment of the mentally ill nor any that has bested convulsive therapy.
Meduna's careful and deliberate study followed the classic principles of clinical observation, hypothesis, and experimentation in animals and then in man. He has given us an effective treatment that is the hope of many seriously ill despite its stigmatization and legislative restrictions. On this anniversary, Meduna deserves our praise.
Fink M (1999), Images in Psychiatry. Ladislas J. Meduna, M.D. 1869-1964. Am J Psychiatry 156(11):1807.
Meduna L (1985), Autobiography. Convulsive Ther 1:43-57, 121-135.
Meduna L (1935), Versuche ber die biologische Beeinflussung des Ablaufes der Schizophrenie: Campher und Cardiozolkr,,mpfe. Zeitschrift fr die gesamte Neurologie und Psychiatrie 152:235-262.
Meduna L (1937), Die Konvulsionstherapie der Schizophrenie. Halle, Germany: Carl Marhold.
Meduna L (1956), The convulsive treatment: a reappraisal. In: The Great Physiodynamic Therapies in Psychiatry, Sackler AM, Sackler MD, Sackler RR, Marti-Ibanez F, eds. New York: Hoeber-Harper, pp76-90.