Two Centuries of Psychiatry's Lessons: No Penicillin, Only Trial and Error
From the ice-pick lobotomy to insulin coma, psychiatry repeatedly claimed an 80% cure rate, yet never found a penicillin for psychiatry — and even today's best drugs still see eight in ten patients drop out of trials.
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There is no penicillin for psychiatry
Modern psychopharmacology was born in the early 1950s, and Andrew Scull stresses that this was not a planned result but a "serendipitous event" — almost purely accidental. It was indeed progress over what psychiatry had before, but the drugs in hand today are only symptomatic treatment, not cure — "we don't have any penicillin for psychiatry." More troubling is the iatrogenic harm: making PTSD patients confront their trauma head-on actually made things worse for many of them; antipsychotics and antidepressants are at best partially effective, and doctors cannot tell in advance who will respond and who will deteriorate, while the people in between must weigh side effects against efficacy.
— Andrew SkullTwenty billion dollars bought not one bit of improvement
Under Stephen Hyman and Thomas Insel, the NIMH invested in mental illness as brain disease, betting heavily on genetics and neuroscience. After leaving office, Insel admitted in an MIT interview: they had funded a great deal of cool science, and after spending 20 billion dollars, the situation of people with mental illness had "improved not one bit." Scull calls this a devastating statement. DSM-5 originally intended to rewrite the diagnostic system based on underlying pathology; by around 2008 the editors gave up and could only carry on the 1980 approach from 1980; before publication Insel and Hyman publicly denounced it as unscientific and useless, and Spitzer and Alan Francis also fiercely criticized its backroom dealings.
— Andrew SkullAmerica's largest psychiatric wards are prisons
People with severe mental illness live on average 15 to 25 years less than others, and that gap is still widening. Scull assigns much of the blame to public policy rather than psychiatry itself: today the three largest inpatient psychiatric "centers" in the United States are the Los Angeles County Jail, the Cook County Jail in Chicago, and Rikers Island in New York. Patients cycle through a three-stage loop — a brief hospitalization, the street or a cheap hotel, then prison. Community care is what Scull calls "a shell game without a P," a con with no replacement facilities, amounting to a return to something like the Dark Ages.
— Andrew SkullWhen you can't cure them, blame their genes
The early asylums were born of intense optimism; the earliest alienists believed that if patients came early enough, 60%, 70%, even 80% could be cured. The actual discharge rate was only 35% to 40%, so each year deposited another cohort of chronic patients, the ratio of new to chronic patients grew steadily worse, and the asylum's image was defined by that chronic patient who "only left in a pine box." By the late 19th century the cure rate by in-house headcount was only 10% to 12%. Faced with the charge "you promised and didn't deliver," the answer turned to blaming the victim: mental illness was a fundamental biological defect, patients were evolutionary throwbacks, degenerates, who could not be released because "they breed like rabbits." This narrative provided the justification for lifelong confinement and sterilization.
— Andrew SkullThe ice-pick lobotomy: psychiatry won a Nobel Prize
Walter Freeman began performing lobotomies in 1936, drawing on the work of the Portuguese neurologist Egas Moniz the year before, for which Moniz won the 1949 Nobel Prize in Medicine — by then with 14 years of experience. Freeman wanted to be the Henry Ford of the lobotomy, mechanizing the operation: first electroshock to render the patient unconscious, then drive an ice pick through the eye socket into the skull, stir, and sever. He toured state hospitals in a van he called the "lobotomobile," teaching as he went, switching from his right hand to his left when it tired, sometimes doing 20 to 30 cases in an afternoon, and boasting he could teach any fool to do a lobotomy in 20 minutes — "even a psychiatrist." He was a neurologist, and held psychiatrists in contempt. The operation was performed from the 1930s into the early 1970s, and finally faded out through generational turnover and antipsychotic drugs.
— Robert Jay LiftonCotton cut out patients' stomachs and claimed an 80% cure
Henry Cotton was a psychiatrist trained by Emil Kraepelin and Adolf Meyer, who ran the New Jersey State Hospital in Trenton. He embraced the theory of "focal sepsis": a low-grade infection in the body releases toxins, and when the toxins reach the brain they poison it. With no antibiotics, the answer was to find the source of infection and cut it out — first pull teeth, the patient doesn't improve; then remove tonsils, still no improvement; so out came stomachs, spleens, colons, and he claimed to have cured 80% of his patients. Wealthy patients came from all over the country. He gave a lecture series at Princeton, published by Oxford University Press and Princeton University Press, and The New York Times called it a major breakthrough. In reality, 45% of those who underwent abdominal surgery died within a year. He died of a heart attack in 1933, and his successor stopped the abdominal operations, but tooth extraction and tonsillectomy continued until 1960 — a dentist who arrived in 1916 pulled hundreds of thousands of teeth and firmly believed Cotton should have won the Nobel Prize.
— Robert Jay LiftonSchizophrenia may not be a disease at all
After the genome was decoded, people expected a Mendelian gene for schizophrenia to be found quickly; it didn't happen. Now with genome-wide association studies, adding up all 300 small genomic variants explains only about 10% of schizophrenia — Scull's verdict is "not very powerful." More troubling is that schizophrenia, bipolar disorder and autism overlap heavily in genetic abnormalities, which undermines the disease categories drawn by symptomatology. He cites the British psychiatrist Robin Murray: schizophrenia is more like the most extreme end of psychosis, a continuum. He speculates that if in ten years psychiatry announced "there is no such thing as schizophrenia," public trust in psychiatry would be badly damaged.
— Andrew ScullNew drugs are no more effective than old ones, and eight in ten quit the trial
The CATIE study (published in the New England Journal of Medicine) compared one first-generation antipsychotic with four newer ones, and concluded the new drugs were no more effective than the old one. The more underrated finding was tolerability: depending on the drug used, 67% to 82% of patients dropped out of the trial, either because the drug didn't work or because they couldn't stand the side effects. In other words, these are already "our best drugs," yet the real-world dropout rate is astonishingly high. The old drug's patent had expired and it was cheap; the second-generation drugs were patented and expensive, in some cases 10 times as expensive, but the higher price bought no efficacy advantage.
In their own words · checked verbatim
And after spending $20 billion, the lot of the mentally ill has improved not one bit, right?
Andrew Skull19:41
when I entered psychiatry, it was a brainless psychiatry. And when I'm leaving it, it's a mindless psychiatry.
Andrew Skull24:04
But community care is a shell game without a P. It's like one of those confidence tricks.
Andrew Skull36:55
He said, you know, I could teach any damn fool to perform a lobotomy in 20 minutes, even a psychiatrist, because Freeman was a neurologist, and he had a lot of contempt for psychiatrists.
Robert Jay Lifton1:00:15
There's this passage in one of his papers where he says, stomachs are like cement mixtures on a construction site and can be dispensed with.
Robert Jay Lifton1:18:07
And when Sackle was told that, he said, yes, that's probably true. They're killing the schizophrenic brain cells.
Robert Jay Lifton1:25:25
And if we use 300 small variations in the genome, we can account for about 10% of schizophrenia. That's not very powerful.
Andrew Scull1:42:33
Between 67% and 82% of the patients, depending on which drug they were on, dropped out of the trial because either the drug wasn't working or they couldn't stand the side effects.
Figures
| Life expectancy gap for people with severe mental illness | Die 15 to 25 years earlier than others, and the gap is widening | 33:44 |
| NIMH investment in the brain-disease direction | 20 billion dollars | 19:41 |
| Actual discharge rate of early asylums | 35% to 40%, against a promise of 60%–80% | 45:18 |
| Share of early 20th-century asylum admissions with general paresis of the insane (GPI, tertiary syphilis) | As high as 25% | 1:05:26 |
| One-year mortality after Cotton's abdominal surgery | 45% | 1:18:07 |
| Explanatory power of genomic variants for schizophrenia | 300 variants explain about 10% | 1:42:33 |
| Share of Henry Cotton's patients who were women | About 70% | 1:57:06 |
| Number of psychoanalysts in North America around 1930 | About 300 | 2:36:28 |
| CATIE trial patient dropout rate | 67%–82% | 3:16:10 |
Glossary
- serendipitous event
- A scientific discovery that was unplanned and stumbled upon by accident.
- shell game without a P
- A phrase meaning community care is a con with no replacement facilities.
- lobotomobile
- The van Freeman used to tour state hospitals performing operations.
- diagnostic creep
- The steady expansion of diagnostic criteria from a clear core outward into the penumbra.
- tardive dyskinesia
- Involuntary facial twitching that appears after long-term antipsychotic use.
- CATIE
- A large trial comparing the efficacy of first- and second-generation antipsychotics.
How to listen
Founders, investors and engineers interested in medical history, psychopharmacology, and how science gets distorted by commerce and hope.
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