… at a 1935 neurology conference in London that Egas Moniz attended, he noted the data presented by Jacobsen and Fulton showing that a leukotomy on two chimpanzees successfully reduced their aggressive behavior without untoward side effects. Learning of this likely prompted Moniz’s bold step to attempt the process, and in 1936, he published his first report of performing a prefrontal leukotomy on a human patient. Moniz refined his surgical methods by fashioning a "leucotome", a surgical instrument with a movable wire loop which he replaced with a steel band. He used this instrument to cut six holes in each of the brain’s two hemisphere’s white matter, severing the connections of the prefrontal cortex to the rest of the brain. Moriz judged the results acceptable in the first 40 or so patients he treated. However, he conceded that patients who had already deteriorated from the mental illness did not benefit much from the operation. Moniz concluded the following, "Prefrontal leukotomy is a simple operation, always safe, which may prove to be an effective surgical treatment in certain cases of mental disorder."Moniz did no long term follow up, and his evaluations of the success of the procedure were short term only. He believed deeply that the benefits of surgical lesions in the frontal lobes, even if some behavioral and personality deterioration occurred, were needed to treat the debilitating effects of severe mental illness. He was the first to write a scientific report of lobotomy as a psychosurgical treatment for severe mental disorders in 1936.In 1939, Moniz was shot by a disaffected patient and as a result was confined to a wheelchair for the rest of his life. In 1949 he received the Nobel Prize, "for his discovery of the therapeutic value of leucotomy in certain psychoses." This procedure consists of cutting the connections to and from the prefrontal cortex, the anterior part of the frontal lobes of the brain. The procedure immediately became popular, as at that time there was not an effective treatment for psychosis… Soon Dr. Walter Freeman developed a version of the procedure [the transorbital lobotomy] which was much easier to carry out. Due in part to this procedural ease, lobotomy was often prescribed injudiciously and without regard for modern medical ethics. Endorsed by such influential publications as The New England Journal of Medicine, lobotomy became so popular that, in the three years immediately following Moniz’s receipt of the Prize, some 5,000 lobotomies were performed in the United States alone, and many more throughout the world. Even Joseph Kennedy, father of U.S. President John F. Kennedy, had his daughter Rosemary lobotomized when she was in her twenties. Freeman performed at least 4,000 lobotomy operations during his career. Since the 1950s, this procedure has fallen into disrepute and is even prohibited in many countries.
Convulsive therapy was introduced in 1934 by Hungarian neuropsychiatrist Ladislas J. Meduna who, believing mistakenly that schizophrenia and epilepsy were antagonistic disorders, induced seizures with first camphor and then metrazol (cardiazol). Within three years metrazol convulsive therapy was being used worldwide. In 1937, the first international meeting on convulsive therapy was held in Switzerland by the Swiss psychiatrist Muller. The proceedings were published in the American Journal of Psychiatry and, within three years, cardiazol convulsive therapy was being used worldwide. Italian Professor of neuropsychiatry Ugo Cerletti, who had been using electric shocks to produce seizures in animal experiments, and his colleague Lucio Bini developed the idea of using electricity as a substitute for metrazol in convulsive therapy and, in 1937, experimented for the first time on a person. Sherwin B. Nuland, having discussed the matter with a first-hand observer in the 1970s, gave the following description of the results of the first use of ECT on a person:
"They thought, ‘Well, we’ll try 55 volts, two-tenths of a second. That’s not going to do anything terrible to him.’ So they did that. […] This fellow — remember, he wasn’t even put to sleep — after this major grand mal convulsion, sat right up, looked at these three fellows and said, ‘What the fuck are you assholes trying to do?’ Well, they were happy as could be, because he hadn’t said a rational word in the weeks of observation."ECT soon replaced metrazol therapy all over the world because it was cheaper, less frightening and more convenient. Cerletti and Bini were nominated for a Nobel Prize but did not receive one. By 1940, the procedure was introduced to both England and the US. Through the 1940s and 1950s the use of ECT became widespread. ECT is the only form of shock treatment still performed by modern medicine.
Manfred Sakel [1900-1957]
Insulin shock therapy or insulin coma therapy was a form of psychiatric treatment in which patients were repeatedly injected with large doses of insulin in order to produce daily comas over several weeks. It was introduced in 1933 by Polish-Austrian-American psychiatrist Manfred Sakel and used extensively in the 1940s and 1950s, mainly for schizophrenia, before falling out of favour and being replaced by neuroleptic drugs. Insulin coma therapy and the convulsive therapies were collectively known as shock therapy. Although insulin coma therapy had disappeared in the USA by the 1970s, it was still being used at that time in some countries such as China, and the former Soviet Union.In 1927 Sakel, who had recently qualified as a doctor in Vienna and was working in a psychiatric clinic in Berlin, began to use low [sub-coma] doses of insulin to treat drug addicts and psychopaths. Having returned to Vienna, he treated schizophrenic patients with larger doses of insulin in order to produce coma and sometimes convulsions. Sakel made public his results in 1933 and his methods were soon taken up by other psychiatrists. Joseph Wortis, after seeing Sakel practice it in 1935, introduced it to the USA. British psychiatrists from the Board of Control visited Vienna in 1935 and 1936, and by 1938 thirty-one hospitals in England and Wales had insulin treatment units. In 1936 Sakel moved to New York and also introduced insulin coma treatment into American psychiatric hospitals. By the late 1940s the majority of psychiatric hospitals in the USA were using insulin coma treatment.
In 1933, the French pharmaceutical company Laboratoires Rhône-Poulenc began to search for new anti-histamines. In 1947, it synthesized promethazine, a phenothiazine derivative, which was found to have more pronounced sedative and antihistaminic effects than earlier drugs… The chemist Paul Charpentier produced a series of compounds and selected the one with the least peripheral activity, known as RP4560 or chlorpromazine, on 11 December 1950. Simone Courvoisier conducted behavioural tests and found chlorpromazine produced indifference to aversive stimuli in rats. Chlorpromazine was distributed for testing to physicians between April and August 1951. Laborit trialled the medicine on at the Val-de-Grâce military hospital in Paris, using it as an anaesthetic booster in intravenous doses of 50 to 100 mg on surgery patients.and confirming it as the best drug to date in calming and reducing shock, with patients reporting improved well being afterwards…
Following on, Laborit considered whether chlorpromazine may have a role in managing patients with severe burns, Reynaud’s Syndrome, or psychiatric disorders. At the Villejuif Mental Hospital in November 1951, he and Montassut administered an intravenous dose to psychiatrist Cornelio Quarti who was acting as a volunteer. Quarti noted the indifference, but fainted upon getting up to go to the toilet, and so further testing was discontinued. Despite this, Laborit continued to push for testing in psychiatric patients during early 1952. Psychiatrists were reluctant initially, but on January 19 1952, it was administered [alongside pethidine, penthothal and ECT] to Jacques Lh. a 24 year old manic patient, who responded dramatically, and was discharged after three weeks having received 855 mg of the drug in total.
Pierre Deniker had heard about Laborit’s work from his brother in law, who was a surgeon, and ordered chlorpromazine for a clinical trial at the Hôpital Sainte-Anne in Paris where he was Men’s Service Chief. Together with the Director of the hospital, Professor Jean Delay, they published first clinical trial in 1952, in which they treated 38 psychotic patients with daily injections of chlorpromazine without the use of other sedating agents. The response was dramatic; treatment with chlorpromazine went beyond simple sedation with patients showing improvements in thinking and emotional behaviour. They also found that doses higher than those used by Laborit were required, giving patients 75-100 mg daily.Deniker then visited America, where the publication of their work alerted the American psychiatric community that the new treatment might represent a real breakthrough. Heinz Lehmann of the Verdun Protestant Hospital in Montreal trialled it in 70 patients and also noted its striking effects, with patients’ symptoms resolving after many years of unrelenting psychosis. By 1954, chlorpromazine was being used in the United States to treat schizophrenia, mania, psychomotor excitement, and other psychotic disorders… The effect of this drug in emptying psychiatric hospitals has been compared to that of penicillin and infectious diseases. But the popularity of the drug fell from the late 1960s as newer drugs came on the scene. From chlorpromazine a number of other similar antipsychotics were developed…
It’s easy to criticize a treatment for its failures. I’ve been critical of the newer atypical antipsychotics. But that criticism is not for the effort. The drugs were developed in an attempt to avoid some of the more difficult and sometimes permanent neurological side effects of the earlier neuroleptics, and they have generally moved towards that goal. The criticism is instead directed towards the minimization by the manufacturers of the unique toxicities of these drugs and overblowing their effectiveness. Even worse, the invasion of clinical medicine by market driven [often downright corrupt] strategies and the attempts to extend the use of these drugs inappropriately is a genuine tragedy for medical science.
Today, in one of my volunteer jobs, I saw a 17 year old boy who I’ve seen for several months. The boy had been quietly psychotic, mostly staying in his room for several years ["he’s always been shy and quiet"]. In spite of constant attacking auditory hallucinations, paranoid feelings, and uncanny mystical ideas, he’d continued high school and graduated with his psychosis largely un-noticed. I initially tried an "atypical" [Resperidol] hoping to avoid side effects, but his symptoms persisted in spite of increasing the dose. I started him on an older drug [Haldol] and at 2mg/day, his symptoms abated. Predictably, today he and his father came to discuss a frightening dystonic reaction, so we spent our time talking about how to manage his EPS if it happened again.