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(Drug information on 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.