Psychiatry, Insane Asylums, Mental Illness, ECT, Lobotomies, Freud & Jung | Lex Fridman Podcast #502
In a Nutshell
Psychiatry's diagnostic system remains symptom-based and unreliable despite decades of research, with no curative treatments for serious mental illness and drugs that are often only partially effective while causing serious side effects. The field's history is marked by repeated therapeutic failures—from lobotomies and insulin comas to modern antipsychotics and SSRIs—that were initially promoted as breakthroughs but proved limited or harmful. While some patients benefit from available interventions, psychiatry lacks biological understanding of mental disorders and has failed to deliver on promises of neuroscience-driven cures despite billions spent.
These notes were generated by AI and may contain inaccuracies.
Andrew Scull is a historian of psychiatry and mental health who has authored books including Madness in Civilization: A Cultural History of Insanity from the Bible to Freud, from the Madhouse to Modern Medicine and Desperate Remedies: Psychiatry's Turbulent Quest to Cure Mental Illness. He has spent decades studying how societies have understood madness, how psychiatry rose to authority, and how that authority was often used with false confidence and catastrophic consequences.
Psychiatry is a profession that tries to deal with an enormously complicated thing: the human mind, the human emotions, and the human ability to attempt to understand the world. It focuses on people where common sense approaches to the world seem to break down—people whose emotional life is filled with turmoil, whose ability to relate to others is badly damaged, or who see things that others think aren't there.
Over the last three quarters of a century there has been some limited progress in dealing with the problems that mental illness creates, particularly for milder forms of mental distress. For more serious forms of psychosis and breakdown of emotional control, progress is more limited than commonly claimed. The advent of modern psychopharmacology in the early 1950s was a serendipitous event that marked an advance over some previous treatments, but available treatments are symptomatic rather than curative.
Psychiatry does not have a psychiatric penicillin for any of the conditions being discussed. Available treatments can help some patients, but the help is quite limited. When treating conditions, iatrogenic problems—things caused by the interventions themselves—can occur. This applies to both psychotherapeutic interventions and drugs.
For example, in treating PTSD, patients are often asked to confront the trauma that provoked their distress. This process is often very fraught and for many patients it actually makes things worse, while for some it helps. With antipsychotics and antidepressants—the two main classes of psychotropic drugs used—treatments are at best partially effective and don't work for a significant fraction of patients. Psychiatrists cannot predict in advance who will respond well to the drugs, who will respond badly, or for which patients the side effects and therapeutic effects are finely balanced.
The fundamental basis of psychiatric diagnosis today was formulated in 1980 with DSM-III. The diagnostic system came into being because psychiatrists had difficulty agreeing with one another about diagnoses. This became clear through professional literature and a study by David Rosenhan called On Being Sane in Insane Places, where pseudo-patients were sent to hospitals and all but one were diagnosed as schizophrenic. The DSM-III task force, led by Robert Spitzer at Columbia, created a tick-the-boxes approach to diagnosis based on symptoms.
The system was based on a list of symptoms—if a patient had more than a certain number of symptoms, they could be diagnosed with a particular disorder. The diagnostic system appealed to drug companies developing treatments, insurance companies needing stable bases for coverage, and patients and families seeking certainty around diagnosis.
The DSM approach relies on symptoms in the way an eighteenth century doctor might diagnose dropsy or fever—conditions that are really constellations of very different things under one label. Reliability means different psychiatrists faced with the same facts reach the same conclusion, but that conclusion may not reflect underlying reality. Validity means the diagnostic system accurately reflects the underlying pathology.
Each iteration of the DSM increased the number of possible psychiatric disorders. The categories became difficult to believe in as real illnesses rather than social constructs. Psychiatrists wanted to root diagnoses in understanding of underlying pathology rather than symptoms, but DSM-5 could not achieve this goal.
Steven Hyman and Thomas Insel, successive directors of NIMH, pushed psychiatry toward understanding the genetics of mental illness and what neuroscience could contribute. Both were invested in the idea that mental illness was brain disease. When Insel stepped down, he stated that after funding enormous amounts of genetic and neuroscience research and spending $20 billion, the lot of the mentally ill had improved not one bit.
The National Institute of Mental Health was founded in the late 1940s with the goal of improving basic research, training people in the field, advancing care of the mentally ill, and producing cures. Starting in the 1990s, during the first George Bush's declared decade of the brain, NIMH focused increasingly on mental illness as purely a brain disease.
The dichotomy between seeing mental illness as a problem of the brain (neurobiology, neuroscience) versus a problem of the mind (cognitive, psychotherapy) represents a category mistake. Human brains are remarkably plastic and develop in response to the environment. Social and psychological factors are embedded in brains, and there is abundant epidemiological evidence that social factors play an important role in the development of illness.
Leon Eisenberg, who had a long career at Harvard, stated toward the end of his career: "When I entered psychiatry, it was brainless psychiatry, leaving it mindless psychiatry." This sums up the way the field has moved, losing insights in the process. Freudians tended to neglect the biological, while the enthusiasm for neuroscience neglected psychological dimensions.
When antipsychotic drugs were discovered in the early 1950s, there was no understanding of how they worked. This led to understanding that the brain wasn't just a set of electrical signals but involved a chemical soup of neurotransmitters. The first neuroscience conventions in the 1970s attracted a few hundred people; now they attract tens of thousands.
Categories like bipolar disorder, schizophrenia, and major depression are beginning to falter. These diagnoses may not be real ways of thinking about the world and may mislead research. Emil Kraepelin developed a distinction between dementia praecox (early dementia) and manic depressive illness. Swiss psychiatrist Bleuler transformed dementia praecox into schizophrenia, though he talked about the schizophrenias because he thought the broad label covered a diverse group of conditions.
DSM-I in 1952 was a 32-page pamphlet with 106 diagnoses heavily influenced by psychodynamic concepts, using broad categories like reactions. DSM-II in 1968 expanded to 185 diagnoses, still psychodynamically flavored, with poor reliability. It added attention to childhood disorders and removed homosexuality as a disorder in a 1974 printing.
DSM-III in 1980 introduced explicit symptom-based diagnostic criteria, a multi-axial assessment system, and an officially atheoretical stance about causes, aiming to improve reliability and research utility. DSM-III-R in 1987 revised criteria and expanded to around 297 diagnoses. DSM-IV in 1994 and DSM-IV-TR in 2000 focused on literature-driven empirical revisions, increased coordination with ICD-10.
DSM-5 in 2013 eliminated the multi-axial system, integrated information into a single non-axial diagnostic list, reorganized chapters, and introduced new and refined entities. The trajectory moved from cause-focused and psychoanalytical to symptom-based, atheoretical, and reliability-driven, with ongoing controversy over medicalization, validity, and categorical versus dimensional approaches.
When constructing DSM-5, the assumption was that with decoded human genome, PCR technology, and understanding of neurotransmission, diagnoses could be recast based on underlying pathology rather than symptoms. By about 2008, this proved impossible, and the symptomatic approach from 1980 had to be retained.
Robert Spitzer and Allen Frances, who had led previous DSM editions, were fiercely critical of DSM-5, saying it was being done in secrecy and wasn't scientific. Thomas Insel and Steven Hyman denounced the document as unscientific and useless before its release.
Drug companies had sometimes behaved unethically with psychiatric drugs, hiding information, manufacturing studies, and manipulating data. They paid billions in damages for these practices. Neuroscience hadn't provided new targets for drug development, leading companies to shift research spending to other diseases. Steve Hyman stated that current drugs aren't really an advance on those found accidentally in the 1950s.
For people with serious mental illness, public policy has created severe problems. A person with serious mental illness will die on average 15 to 25 years before the general population, and this gap is growing. The three largest centers of inpatient psychiatric care in the United States today are the Los Angeles County Jail, Cook County Jail in Chicago, and Rikers Island in New York. Prisons aren't equipped to deal with serious mental illness.
Asylums were founded during a period of enormous optimism that mental illness could be cured by providing a therapeutic environment, coaxing patients to work, and creating systems where they could learn to control themselves. The earliest alienists thought they could cure 60, 70, 80 percent or more of patients if treated early. Asylums were meant to rescue people from horrendous conditions in prisons and jails.
Community care, promised as a replacement for asylums starting in the late 1960s, proved to be a shell game. No substitute community facilities were created for dealing with the seriously mentally ill.
Psychosis involves people who have lost touch with reality, experiencing emotional and cognitive turmoil. Those affected lose the ability to connect with other human beings, causing their social skills to atrophy. Contemporary psychiatrists refer to the positive and negative symptoms of schizophrenia, but underlying the definition is a detachment from reality. This manifests as hearing voices, seeing visions, thinking people are plotting against you, or believing the television is talking directly to you. The consequences affect how individuals connect to the rest of the world and their emotional lives. Emotional life flattens out, language capacity deteriorates, and the ability to relate to other people either vanishes or becomes caught up in the web of delusions where people around them are seen as plotting against them or doing terrible things to them.
The Greeks and Romans recognized different forms of insanity, using the term melancholia which survived as a form of depression. Major depression has become a catchall category embracing both milder forms of emotional distress along with what melancholia referred to, which was depression with psychotic features and loss of contact with everyday reality. Dementia was also recognized by the ancients as the loss of mind.
In the 19th century, neurosis meant things rooted in the brain, while psychosis referred to things from the mind or psyche. Sometime in the late 19th century these meanings crossed over. In the present, the distinction separates the most severe forms of mental disorder, including Alzheimer's disease and other forms of dementia, very serious depression, and bipolar disorder, from other conditions.
Bipolar disorder involves people who oscillate between extreme mania, characterized by not getting any sleep, talking at an extraordinary rate, behavior that's very hard to tolerate, and exhausting themselves to the point of possible death from exhaustion, alternating with periods of depression. This was initially captured as manic depressive illness, later evolving into bipolar disorder with depression separated out as major depression separately.
Neuroses include phobias where people cannot go outside because they find it too frightening, or milder phobias such as not being able to get in an airplane because it might crash, or school phobia where school is overwhelming. Hysteria was a disorder that initially attracted Freud, and a book was written on this topic.
The asylum era was born in a period of intense optimism with claims to cure vast numbers of patients being overblown. Early asylums did good work and some patients recovered, but they weren't discharging 80% of their patients as claimed. They were discharging 35 or 40% of their patients, leaving behind a batch of chronic patients each year. Over time, the ratio of new patients to chronic patients got worse and worse. The image of the asylum declined drastically as they became overcrowded, conditions deteriorated, patients were often abused, and psychiatrists didn't know what to do with them.
By the late 19th century, psychiatrists had promised 70% or 80% cures, but calculations showed more like 10% or 12% when accounting for chronic patients mixed with new admissions. The explanation came through blaming the victim, claiming mental illness was a fundamentally biological condition and that these people were evolutionary throwbacks. The idea of degeneration emerged, suggesting these patients were degenerates with inferior biology who couldn't be released because they breed like rabbits and lacked self-control due to their diminished humanity.
This narrative provided justification for locking up people in asylums that wasn't therapeutic at all, just keeping them out of the way. It led to the justification of sterilization, with the argument that maybe patients could be released if they couldn't breed. The speaker's own state was one of the pioneers in this process and continued to sterilize mental patients up until about 1960. By the 1960s, over 60,000 sterilizations had been performed in the US, with California performing a disproportionately high number.
A British psychiatrist stated that if his patients had been puppies, they would have been tied up in a sack with lead weights and thrown in a pond to drown. This kind of language was very dangerous. California's sterilization law was advocated for in North America, Britain, and much of Europe. While there were checks and balances in democratic systems that prevented mass support for euthanizing patients, when the Nazis came to power in Germany, they seized on these notions. The mentally ill were labeled as useless eaters consuming resources with lives not worth living. Hitler started the T4 program after Tiergartenstraße 4, where the mentally ill were the first to suffer from the Final Solution. As many as a quarter million people may have been killed in the mass killing of the mentally ill, where the technology of the gas chamber and disguising it as showers was developed. Patients were taken to psychiatric centers, systematically put to death, with crematoriums and black smoke, and local people referred to the buses bringing them in as killing crates.
America financially supported German psychiatric researchers with deep Nazi ties, including Ernst Rüdin who was the key architect of Hitler's mass sterilization and extermination laws. The Nazis borrowed American narratives that these were lesser biological beings. The Rockefeller Foundation recognized that mental illness was an acute social problem, very costly to the state. Before World War II, science was an orphan that didn't get much government money, and medicine even less so. The Rockefeller Foundation decided to concentrate its resources and chose psychiatry as the area to invest in, partly because scientific research in psychiatry was backward, partly because it was a pressing public problem, and partly because several trustees had direct experience of mental illness in their families.
Rockefeller spread its money widely because it didn't know where to spend most of it. It supported psychotherapeutics, therapeutic experiments, and work in genetics. One geneticist supported was Ernst Rüdin in Germany, the leading German researcher in genetics and mental disorder. Rüdin, having absorbed lessons from California about sterilization, became an enthusiastic proponent of that and then a supporter of murdering mental patients.
A series of therapeutic experiments were conducted on people who were shut up in a double sense: locked away and their voices not heeded because their complaints were seen as products of their madness. In the first five decades of the 20th century, people with various motivations, including the desire to improve the lot of the mentally ill, engaged in uncontrolled experiments with terrible results. The science behind these was shaky but existed.
The clearest case of these experiments breaking down was lobotomy, the idea that psychotic breakdowns could be solved by excising part of the brain. Initially this was done by drilling holes in the skull and injecting alcohol or using what looked like a butter knife to break connections between the brain. Later, Walter Freeman, who aspired to be the Henry Ford of lobotomy, invented the ice pick lobotomy. This involved using an ice pick in the orbit of the eye after rendering someone unconscious with two or three electric shocks, then banging it through the bone and wiggling it about to sever connections.
Freeman started his work in 1936, borrowing from Portuguese neurologist Egas Moniz who won the Nobel Prize in medicine in 1949 for lobotomy. Freeman's particular specialty after the war became the ice pick lobotomy because there were over half a million patients in America's mental hospitals. He was convinced this operation was a cure-all and traveled around in a camper truck he called the Lobotomobile, descending on state hospitals in the summer to teach them how to perform ice pick lobotomies. He was ambidextrous and could do 20 or 30 lobotomies in an afternoon, boasting that he could teach any damn fool to perform a lobotomy in twenty minutes, even a psychiatrist.
Lobotomy really took generational change to die away. Some lobotomists continued operating into the sixties and early seventies, but the younger generation rebelled against this after becoming acquainted with the worst failures: people on the back wards who were incontinent and basically zombies who had lost all mental power. By then they had a different treatment in the form of antipsychotic drugs which looked more like what regular medicine was doing and didn't have the horrible overtones.
In the popular mind, the most famous instance of telling the public about these interventions was the film of Ken Kesey's novel One Flew Over the Cuckoo's Nest, where Jack Nicholson is given ECT in a very dramatic rendition of what that was not really like by the 1970s, and then finally lobotomized, with the film ending with him being smothered to death. This fixed in the public mind some of the images of these things and gave electroconvulsive therapy such a bad name.
Insulin shock therapy from 1933 to the 1960s involved putting patients in deep hypoglycemic comas using large doses of insulin. Psychiatrists who were ambitious and wanted to think of themselves as therapeutic agents found it unattractive to just sit passively and contain patients, so they looked for biological interventions to ameliorate conditions they still saw in largely biological terms.
One of the few diagnostic triumphs of psychiatry in the early nineteenth century was distinguishing patients suffering from general paralysis of the insane. This involved paralysis, the gradual loss of motor control, ability to walk, swallow, and talk, accompanied by bizarre psychiatric symptomatology where people thought they were Napoleon, Jesus Christ, or the richest and sexiest person in the world. At the turn of the twentieth century, as many as 25% of people being admitted to asylums were suffering from GPI. The discovery was made at Rockefeller Institute that the organism causing syphilis was residing in the brains of people suffering from GPI. This was tertiary stage syphilis, which was like AIDS in the late nineteenth century.
Syphilis lurks the way chicken pox virus lurks and can surface years later. It sometimes attacks the heart and people drop dead of a heart attack in their forties, or it attacks the central nervous system, the spinal column and brain, causing paralysis and psychiatric symptomatology. This discovery suggested that mental illness might have an infectious origin.
Tertiary syphilis GPI went on to win for somebody who developed a treatment a Nobel Prize, one of only two awarded for psychiatric innovations. The other was for lobotomy. The other was giving people malaria to cure their syphilis. An Austrian doctor named Wagner-Jauregg had long thought that fever could be used to cure mental illness. He tried rat bite fever and giving people typhoid vaccine that creates a fever, to no avail. Toward the end of World War I, an Italian soldier with malaria was captured and brought to him. He extracted the malarial blood and injected it into patients with GPI, claiming it cured them. Those claims were wildly exaggerated, but they were widely accepted and malarial treatment spread to Britain, Germany, and the United States. Sometimes it was vials of malarial blood, but very often mental hospitals had actual colonies of malarial mosquitoes. Patients would be put in a straitjacket in a room where mosquitoes would bite them, causing them to develop malaria. Wagner-Jauregg got a Nobel Prize for this in 1937 because GPI was invariably fatal.
Julius Wagner-Jauregg developed malaria fever therapy as a treatment for general paralysis of the insane, which was caused by syphilitic infection. The theory held that either the induced fever stimulated the immune system to attack the causative agent, or that the high fever directly killed the malarial parasites in the brain. This treatment was widely used for decades despite the absence of controlled trials and statistical sophistication. The discovery of penicillin ended this approach, as it provided a genuine cure rather than the temporary fever induction method.
The work of Louis Pasteur, a chemist rather than a physician, and Robert Koch in Germany established the bacterial origins of disease in the late 19th century. This led to major public health advances including vaccines for diseases like rabies, even before antibiotics were developed. Joseph Lister adapted Pasteur's theories to surgery, demonstrating that carbolic acid could prevent post-surgical infections by killing microorganisms. His colleagues initially dismissed the idea of unseen microbes, but Lister prevailed, leading to the transition from antiseptic to aseptic surgery.
These represented clear examples of medical progress, in contrast to the more ambiguous advances in psychiatry. The discovery that 25% of mental hospital admissions were actually suffering from infectious diseases helped connect psychiatry to the laboratory-based model of medicine.
Emil Kraepelin, who established the fundamental distinction between schizophrenia and bipolar disorder, began considering whether mental illnesses might have infectious origins. Henry Cotton, trained by both Kraepelin and Adolf Meyer, became superintendent of the New Jersey State Mental Hospital at Trenton. Cotton championed the theory of focal sepsis, proposing that low-grade infections released toxins into the bloodstream that poisoned the brain.
Without antibiotics, Cotton pursued what he called surgical bacteriology to eliminate these infections. He began by extracting teeth, then tonsils, and progressed to removing stomachs, spleens, and colons. Cotton claimed an 80% cure rate, attracting wealthy patients from across America. He lectured at Princeton University, and his work was published by Oxford and Princeton University Presses, with the New York Times hailing it as a breakthrough.
In reality, 45% of patients receiving abdominal surgery died within a year. Cotton described stomachs as dispensable cement mixers. Patients who had all their teeth removed could be identified as former mental patients. Cotton died of a heart attack in 1933, and his successors abandoned abdominal surgery but continued extracting teeth and tonsils until 1960. The hospital dentist interviewed for this research had extracted several hundred thousand teeth and remained convinced Cotton deserved the Nobel Prize.
The discovery of insulin in the 1920s transformed type 1 diabetes from a death sentence into a manageable condition, representing genuine medical progress. Manfred Sakel, working with drug addicts in Germany, observed that mild insulin-induced comas helped with withdrawal symptoms. When he moved to Austria, he applied this approach to schizophrenia, putting patients into comas lasting hours or days, revived by intravenous glucose. Sakel viewed seizures during these comas as therapeutic signs and claimed an 80% cure rate.
Sakel demonstrated the treatment at Harlem Valley Mental Hospital in 1936 and established a lucrative New York practice. The therapy required intensive nursing and medical monitoring due to the risk of permanent coma or death. Evidence suggested it killed brain cells, which Sakel claimed was beneficial because it eliminated schizophrenic brain cells. The treatment was never subjected to randomized controlled trials until the 1950s, when it failed and was abandoned.
John Nash, the mathematician portrayed in A Beautiful Mind, received insulin coma therapy at Trenton State Hospital, the same institution where Cotton had practiced. Patients experienced thrashing, moaning, and convulsions before entering comas, requiring up to sixty treatments. The mortality rate was 1-5%, and the treatment caused significant brain damage and obesity.
An Austrian psychiatrist theorized that schizophrenia and epilepsy were antagonistic conditions, proposing that artificially induced seizures might eliminate schizophrenia. Initial attempts using camphor caused abscesses and proved ineffective. The psychiatrist then used Cardiazol or Metrazol, which produced grand mal seizures with complications including vertebral and hip socket fractures. Patients described feeling on the brink of death between injection and seizure, a sensation lasting from two to ten minutes.
Ugo Cerletti and Lucio Bini developed electroconvulsive therapy after observing pigs being slaughtered at the Rome slaughterhouse, where electric current applied to the head caused convulsions without killing the animals. Initial experiments on dogs with electrodes on the head and anus caused cardiac arrest. When applied to the head only, the current produced seizures without fatality.
Cerletti and Bini tested the procedure on a homeless man found at the Rome train station. Their first attempt used insufficient current and had no effect. When they discussed increasing the current, the patient protested that another shock would be deadly, but they proceeded anyway. The patient experienced a grand mal seizure with the typical complications of fractures and breathing cessation before spontaneously resuming breathing and showing improved contact with reality.
ECT proved ineffective for schizophrenia but appeared useful for severe depression, particularly suicidal cases. The unmodified form used through the 1950s and into the 1960s was associated with fractures and memory problems. In mental hospitals of the 1940s and 1950s, ECT was often used more as a behavioral control mechanism than a therapeutic intervention, as patients would modify their behavior to avoid repeated treatments.
Muscle relaxants were introduced to prevent the violent thrashing that caused fractures, though this required anesthesiologists and breathing support since the relaxants also paralyzed respiratory muscles. ECT remains controversial due to memory problems and concerns about brain damage from passing electric current through the brain. The treatment often requires repetition as maintenance therapy, providing temporary symptom relief rather than cure.
Treatment-resistant depression refers to cases where patients do not respond to medication. ECT faces significant legal restrictions in many states, with California requiring voluntary consent even for involuntarily confined patients. A powerful opposition movement exists, comprising psychiatrists, former patients, and others suspicious of medical interventions, with the Church of Scientology maintaining a museum called Psychiatry: Industry of Death.
Widespread distrust of medical science and pharmaceutical companies has grown substantially, with some groups remaining unpersuadable by evidence. The Scientologists represent an extreme example of this position. Broader distrust of vaccination has contributed to general suspicion of science and medicine. Concerns exist that four years of institutional disruption could exponentially increase mistrust while destroying ongoing clinical trials, eliminating years of accumulated knowledge, and halting the training of new scientists, potentially resulting in a lost decade of medical progress.
Diminishing people's trust in science represents a profoundly devastating cultural development with consequences that will affect future generations. Trust in institutions can be built up over time but destroyed very easily. Regarding whether psychiatry is in crisis, genetics was supposed to provide a clear picture of the origins of various mental diseases since they appear to run in families. The expectation was that decoding the human genome would quickly reveal Mendelian genes or sets of genes for conditions like schizophrenia, but this hasn't occurred.
Genome-wide association studies have shown that using three hundred small variations in the genome can account for approximately ten percent of schizophrenia, which is not very powerful. Psychiatric genetics has tended to undermine distinctions made based on symptomatology, revealing considerable overlap in genetic abnormalities that heighten susceptibility to bipolar disorder, schizophrenia, or autism. This suggests these aren't distinctive entities in the traditional sense.
Schizophrenia appears to represent the extreme end of psychosis rather than a discrete condition, existing on a continuum. Some leading psychiatrists speculate that in ten years there may be recognition that there's no such thing as schizophrenia or bipolar disorder as currently conceptualized. Such a development would likely have negative effects on people's trust in psychiatry.
Trust in institutions, science, and history is vital across multiple domains. More humility and less arrogance are needed, along with greater willingness to confess the limits of what can be done. There's danger in enthusiasm and a need for more skepticism when told something represents a breakthrough. Science journalism and medical journalism tend to hype developments, and when the hype proves unfounded, this undermines trust.
Ketamine and psychedelics are currently being promoted as miracle cures for depression, but the evidence for this is enormously weak. This pattern of overblown rhetoric has been seen repeatedly, including claims of 80% cure rates for Cotton's work, insulin coma therapy, and early asylums. Reality shows that progress usually comes in small steps, though occasionally dramatic shifts occur, such as with penicillin.
Penicillin and other antibiotics became widely available during a period when they hadn't been overused, providing immediate treatment for conditions like strep throat without risking heart valve damage. AI may help in developing new treatments but could also prove to be a double-edged sword.
Beyond science journalists, major journals like Science and Nature also tend to foreground research that makes a big splash. Negative findings, which are very important for helping avoid mistakes, are unlikely to be published in prominent journals. The publication process itself, along with conferences and journal editors, creates incentives that favor certain types of results.
Having lots of scientists working on problems across different sites serves as an important check on enthusiasm and premature claims. Multi-centered research is valuable because different researchers may be partially right but not fully correct, and others following similar ideas may get closer to the truth. Funding agencies often make it difficult for maverick scientists to get support, though history shows many cases where initially unsupported research later proved valuable.
Ken Kesey wrote his novel based on his experience working at a veterans' hospital in Menlo Park. The book and the 1975 film differ in point of view, tone, and focus. The novel is weirder, more political, and centers on Chief Bromden's inner world and the combine, while the film is more naturalistic, character-driven, and positions McMurphy as the central hero.
Mental hospitals have had a patchy and complicated history. Veterans' hospitals were largely created after World War II, when American psychiatric casualties among troops were two to three times higher than in World War I. The book was different from the film, with the latter changing various elements.
The film recreates the poverty of the environment and the way staff often put patients down, didn't listen to them, poked fun at them, or were physically abusive. The general boredom of institutional life is difficult to represent on screen. The abusive element was almost inevitable given that the lowest-paid, least-respected ward attendants had the most contact with patients, with few RNs present and minimal physician involvement.
Almost invariably, women received the brunt of experimental psychiatric treatments. Approximately 70% of Henry Cotton's patients were female. Lobotomy records from various hospitals consistently show 60-70% of patients were female. ECT tends to be used heavily on women, partly because it's primarily applied to serious cases of depression, which is diagnosed more frequently among women than men.
Men tend to receive different diagnoses, with personality disorders being very common and more frequently diagnosed in men, as is ADHD. The film One Flew Over the Cuckoo's Nest helped end interest in ECT for decades, except among a small handful of enthusiasts, and likely continues to create hesitation about the treatment.
ECT has a terrible history from the 1940s through 1960s, with documented abuses including CIA-funded experiments by Ewen Cameron in Canada, where patients received multiple ECT sessions daily, reducing them to states where they couldn't walk, talk, or feed themselves and were incontinent. Many were left permanently damaged.
However, some patients describe ECT as lifesaving, particularly those on the brink of suicide with long-running depressions. Recent controlled trials provide enough evidence to suggest it works in certain cases, though the mechanism remains unknown since it's a purely empirical treatment.
Unlike treatments with some theoretical understanding, such as surgical cancer removal or blood pressure medication, ECT lacks any explanatory framework for why it works. This absence of understanding tends to put people off, and for a long time ECT was grouped with lobotomy, insulin comas, and deep sleep treatments as interventions to be discarded.
The conception for writing Desperate Remedies originated in 1981 during a Guggenheim Fellowship at the Wellcome Institute in London. The initial plan was to study treatments from the 1920s and 1930s, but the project evolved over forty years into a comprehensive examination of psychiatry from its origins to the present. This extended timeline allowed incorporation of developments from 1980 onward, which proved essential to the overall picture.
The book was published in 2022, forty years after the initial research concept. Having multiple projects running simultaneously helped maintain productivity and interest, allowing work on different topics when one became tiring and enabling ideas to percolate across projects.
Psychiatry remains engaging because it involves tremendous human suffering that exists in every society studied, from ancient Greeks and ancient China to contemporary times. While forms vary and treatments differ across cultures, every society must cope with people who deviate significantly from culturally appropriate norms.
The difficulty of studying mental illness and its complex nature creates space for examining issues in complicated ways. The limits of current knowledge mean there's substantial intellectual territory to explore, attracting very smart people to the field, though much remains to be understood.
Late nineteenth-century psychiatry, confined to mental hospitals, had become very biological in orientation. However, many people experienced mental troubles including sadness, confusion, loss of social relationships, and grief that didn't require hospitalization but caused significant distress.
Nineteenth-century America spawned several new religious movements that addressed mental health concerns. The Seventh Day Adventists established a sanitarium for depressed congregants that was later taken over by the Kellogg family. This facility attracted prominent figures including Abraham Lincoln's widow, Tarzan author Edgar Rice Burroughs, and Henry Ford, and emphasized connections between diet, defecation, and mental stability.
Mary Baker Eddy developed Christian Science, which taught that disease doesn't exist and can be prayed away through sufficient faith. Christian Science achieved considerable followers, disproportionately women, and treated many people suffering from milder mental disorders. Mark Twain was thoroughly dismissive of Eddy and her teachings.
The Emmanuel Movement, centered around the Church of the Emmanuel in Boston, represented another religiously-based attempt to help the mentally troubled by combining medical and religious approaches. Doctors involved eventually withdrew, believing the enterprise was veering too far from medically-based therapeutics.
Neurology emerged in America after the Civil War, which provided naturalistic experiments on brain and nervous system trauma from bullet wounds. Neurologists claimed expertise in brain and nervous system disorders, including insanity, which was viewed as a brain disease. This created conflict with psychiatrists during the 1870s and 1880s.
Neurologists couldn't access asylums where the most seriously ill patients were housed. Their outpatient practices gradually included people with functional mental disorders alongside those with conditions like multiple sclerosis. Initial treatments involved drugs, electricity (not ECT, but static electricity), and tonics.
Silas Weir Mitchell developed the rest cure, which became the most notorious treatment approach. The transcript cuts off mid-sentence while discussing Mitchell as one of the leading figures in American neurology.
Silas Weir Mitchell, one of the leading lights of American neurology, develops complete bedrest, lots of calories, lots of food, complete lack of intellectual stimulation. Supposedly, this is going to cure you. Mainly aimed at women. Virginia Woolf was one of the people subjected to this. She claimed it practically drove her mad or made her worse.
Weir Mitchell wrote two popular bestsellers, self-help books. One was called Wear and Tear. The pace of modern life, the telegraph, the railway was all too much. Your nervous system was overstressed. Either your batteries ran down, that was one analogy, or you overtaxed your system and went bankrupt. Wear and tear, that was the problem. The solution was Fat and Blood. That was the title of the other book. You got scrawny, nervous, twitchy. And what you really needed was to build back up your strength, including your nervous strength.
There were also these mental healing groups that were religious, and they're all around at the beginning of the 20th century. In 1909, a Viennese gentleman and two of his close colleagues travel across the Atlantic on a German steamer and arrive in New York and then transport themselves up to Worcester, Massachusetts, where Clark University is celebrating its 20th anniversary. Clark University was then set up to copy the German research university. The only comparable example at the time was Johns Hopkins in Baltimore, and Hopkins developed the leading medical school of the time borrowing from that German concept of mixing research and teaching and patient care.
Many of the in-house histories of psychiatry portray this as the Freud conference. But it wasn't. Freud was almost an afterthought of the conference. The head of Clark was a psychologist, and he was interested in Freud, but actually there were about thirty speakers at the Clark conference, two Nobel Prize winners in physics, Franz Boas, who was the leading anthropologist of his generation, and a host of other scholars, including a couple of Freud's fierce critics, one of whom, Stern, was on the same boat as him. And they avoided one another like the plague.
Freud delivered his lectures in German, and the audience, that wasn't a problem for the audience 'cause they'd all learned German so they could read German literature on medicine.
William James attends one of Freud's lectures and has a conversation with him. William James is one of the people thinking about the psychology of the human mind in interesting ways. He's not impressed by Freud, and he also has a bad heart condition. He dies not all that long afterwards.
A handful of people are impressed, some of the neurologists. Freud's lectures explicitly attack religiously based psychotherapy, says psychotherapy is like a surgical operation on the mind. And only us doctors or only us thoroughly trained people can practice it. The lecture is on psychoanalysis. It's five lectures. They're published subsequently, and he makes a very important convert there. James Jackson Putnam is a Boston Brahmin, one of the upper-class Bostonians who's extremely well connected and is professor of neurology at Harvard, and he becomes a Freudian at that conference.
Mainstream American psychiatry pays very little attention to Freud's arrival on the scene. And when he becomes a bit more visible, they tend to be very dismissive. They regard the idea of talk therapy for something they regard as a biological condition as a ridiculous idea.
Sigmund Freud is widely acknowledged to be the father of psychoanalysis. He has a bunch of ideas, one of which is there's this unconscious mind that is the source of many of our behaviors. And then psychoanalysis is a way to delve deep into that mind, and the tools he used to do that is talking. Freud was trained as a neurologist himself and studied under the most famous late nineteenth-century neurologist Charcot in Paris and translated Charcot into German and endeared himself to Charcot by doing that.
His Viennese colleagues didn't think much of Charcot, and they didn't think much of Freud's ideas either. So he had a bit of a hard time, but he did develop a successful practice in the sense that patients came to him.
Freud was accompanied by two of his close disciples to the Clark conference, one of them Carl Jung. Jung was then anointed the crown prince. He was supposed to inherit Freud's enterprise until the men had a very serious falling out just a little bit later in 1913, and Freud and Jung went their separate ways.
Freud, as one of his close friends and collaborators put it, was a great hater. If you fell out with Freud, it was bad news. You were excommunicated if it was Adler, but Jung especially. Jung was Swiss and he worked in the major mental hospital in Zurich, and he was attracted to psychoanalysis and to Freud. And for the first few years there, there was this obvious close alliance.
Jung was the person who actually persuaded Freud to go to America. Freud initially had a very low opinion of America. He said it should be renamed Dollaría because it was only interested in the dollar. And American women were far too pushy and powerful, and American food was dreadful and it poisoned him, and on and on.
Freud's academic career had been failing in Vienna, and he faced a prospect of either having to emigrate to America, which he regarded with horror in the 1880s, or perhaps reviving his career by going and studying under the most famous neurologist of the era, Jean-Martin Charcot, who was then delivering lectures on hysteria in Paris. And so Freud went and spent some months there and came back imbued with Charcot's ideas about hysteria and found a Viennese medical establishment.
Freud had a close friend named Josef Breuer. And Breuer was more senior, had a very large practice, and referred patients to Freud. And the two of them began to be interested in this problem of hysteria. Breuer had treated a woman who's now known as the sort of foundation patient for psychoanalysis, who was known to us as Anna O. She was actually Bertha von Pappenheim, but that was hidden for a long time. A lot of these patients had pseudonyms because obviously the cases exposed a lot about their inner psychology and quite reasonably, even without the modern concerns about privacy, there was a reluctance to identify them.
Anna O. had nursed her father. She was Breuer's patient, not Freud's. She'd nursed her father through an illness, and he'd ended up dying, and she developed various physical symptoms that troubled her a great deal and was also somewhat depressed. And Breuer and Freud dealt with that by developing a notion that what she was suffering from was repressed memories and trauma. And this would become central to psychoanalysis, the idea of half-muttered memories lurking in your subconscious that emerged in distorted forms of psychological symptoms and ways of being in the world that were disruptive.
Freud, of course, develops a much more elaborate theory of this in years to come. And Breuer collaborate on a book called Studies in Hysteria, and they're a series of case vignettes in there of patients Freud has treated. And he develops the notion that people have these past experiences. Initially, he thinks they're real, that they've, for example, been sexually assaulted as a child, and that they can't face that, and so they hide it away from themselves. But they can't completely, so it emerges in this tortured series of forms. And as things develop, the notion of resistances emerges, that you can't easily retrieve these memories, and indeed, you resist them surfacing, and you have a hard time acknowledging them. And only with long and painful work will it become possible for you to bring them from the unconscious into the conscious world, you learn to cope with them in a different way and your personality is transformed and you're made better.
The early experiences have a dramatic effect. To the extent we abolish this distinction between mind and body and acknowledge that they are closely tied together, traumatic experiences in childhood, various socialization experiences, loss and so on deeply mark the human psyche, and can have long-term effects that are very powerful.
As Freud begins to develop his theories, he more and more comes to see at first the libido, which gets sort of transformed into the sex drive, and sexual experiences and the repression of sexuality and the modification of sexuality as people grow. All of that enters the picture. It's one of the things that ends up dividing Freud and Jung, Jung somewhat because Jung downplays that sexual side of things after the break.
Freud develops a very complicated theory of mind initially reflecting his training as a neurologist. He tries to write an essay which survives called Project for a Scientific Psychology, and the scientific psychology is gonna tie psychology back into neurology. But he abandons that, and once he's abandoned that, he goes on to develop an increasingly elaborate theory. He writes The Interpretation of Dreams, for example, because he begins to regard dreams as an arena where these hidden memories, these suppressed things reemerge in disguised form in your dream life. And so that book marks an important step forward. He becomes interested in things like slips of the tongue, so-called Freudian mistakes, as seeing those as revealing what really is hidden from you. And so there's this very elaborate dissection of things that relies upon long extended talk therapy.
Freud builds a model of how this whole mind thing works. There are three interacting parts of the personality. First the id, which is the primitive entirely unconscious driven by pleasure principle seeking immediate gratification or basic drives such as sex and aggression. There's the ego, which is the rational mediator operating under reality principle balancing the id's demands with external reality. And finally, the superego, which is the internalized moral standards and ideals producing guilt or pride and striving for perfection. That is broadly speaking the structure that Freud ends up with, and the conflicts between these entities and the ways they interact are obviously the thing that creates your mental universe, your way of being in the world and in many cases creates pathology, which through the process of psychoanalysis you can transform grotesque unhappiness into ordinary unhappiness.
Initially, Jung gets one of the heirs to the International Harvester fortune as a patient, and the McCormick family are as rich as the Rockefellers and the Carnegies and the Vanderbilts of that world. This guy is a US senator who ends up committing suicide in 1925 after a lot of treatment from Jung when he fails to win reelection to the US Senate. He kills himself in Washington in the interregnum.
Jung also gets another one of that brood. One of the Rockefeller daughters, Edith Rockefeller marries a McCormick. And she has a lot of psychological issues, and she tries to get Jung to move to Chicago promising him she'll set him up in a mansion with lots of her friends as his patients, and Jung has no interest. So then she finally persuades him to come to New York and accompany her on the liner across to Zurich to be treated. She's agoraphobic, and so she has a hard time being out of her little cocoon. So she's treated there as an example of how peculiar she was. She occupies a huge array of suites with all her servants and so on in Zurich. And she takes a train journey, it's a stopping train, and her chauffeur follows the train in the Rolls Royce in case she has to jump out of the train at a station 'cause she can't bear it anymore. And she becomes a Jungian analyst, but she's very wealthy and she writes big checks to Jung which is the important thing.
Jung attracts Paul Mellon and his wife Mary. And so Jung's works are published by Princeton University Press with a subvention from that Mellon Foundation. So it's a long-running thing. Freud doesn't get patients quite that rich. He gets some rich Americans.
Freud's ideas became quite popular among the intellectual and artist class in the 1920s in America. World War I saw the breakdown of many soldiers from something that came to be labeled as shell shock. The label shell shock intimates the first theories about its origin, which was that shells bursting near you and bombs bursting near you shook up your body and your brain and created some physical damage that then accounted for the symptoms of shell shock: your mutism, your blindness, your constant shaking, your nightmares, all of that. But it became increasingly apparent that shell shock was actually a psychological thing. The trauma of war in significant number of cases brought about mental breakdowns. And in thinking about that, Freud's ideas about the unconscious mind and trauma and its connection to symptomatology acquired a new significance for a lot of people in that period.
And then after the war, among a certain smart section of society, those ideas developed a considerable purchase. Psychiatrists who were mostly stuck in the asylums dealing with psychotic patients wanted nothing to do with these ideas and this talk therapy. The mainstream psychotherapy which was mostly in a clinical setting—Freud's ideas were not popular.
The only partial exception to that was the mental hospital in Washington DC—the only federal mental hospital, St. Elizabeths. William Alanson White, who was then the superintendent, was somewhat sympathetic to Freud's ideas and tried a bit, but you're talking about thousands of patients and the idea of talk therapy for them is obviously out of reach, plus they are much more severely disturbed.
Novelists, painters, artists, playwrights, and the audience for those elite forms of culture do tend to embrace Freudian ideas. Sex sells in the theater and on the movies. But beyond that, part of Freud's appeal to everybody, it was something he lamented at one point. He said, "You know, my case histories read like short stories. Like works of fiction. And in that sense, people think they lack the stamp of serious science. But I'm driven to that because that's how I unpack what's going on."
Psychoanalysis is telling stories. It's getting people to recover stories, recover memories, to rebuild. And its elements of psychological conflict and hidden motives and so forth naturally very appealing to people writing novels. People writing plays. People doing screenplays. And for artists of the modern sort the idea that we can extract things from the subconscious—Surrealism and the like, for example, are clearly very heavily influenced by Freudian ideas.
It's important to know circa 1930 there are probably three hundred psychoanalysts in North America. If they each do classical psychoanalysis involving five hours a week, they can't treat that many patients. A few thousand when there are hundreds of thousands in the hospitals.
What changes that is Hitler starts killing off Jews and killing off psychoanalysts. The ones who can escape, some of them go to England and some come to America. The most famous escapee is Freud himself and his daughter Anna. Princess Bonaparte who's one of Freud's great supporters bribes the Nazis to get him out. And he travels by train to London. Very sick with cancer of the jaw as he has been since the mid-'20s. So he sets up shop in London and Anna succeeds him really as one of the central figures in British psychoanalysis. But other analysts come here to America. So the numbers of analysts probably by 1940, America's not yet in the war, have a bit more than doubled. And more importantly psychoanalytic training has become much more organized here. The institutes outside the universities control psych... And universities are not yet the knowledge factories they become after the war. And that's a crucial mistake that psychoanalysis makes. It's great because it controls its training completely. The bad thing is when the center of gravity moves to the university it's not there and either resists being incorporated or the university resists incorporating it. So I think that's a structural weakness for that.
What really transforms things is World War II. Five fifty minute hours famously. They last fifty minutes 'cause then there's ten minutes for four analysts to recover before the next patient arrives. You are free associating on the couch and gradually being coaxed to see as material emerges what you're hiding from yourself. Initially they tried—this is in their early early days—that they tried hypnosis. But Freud came back from Paris bringing with him the idea that hypnosis was the way forward. But after the break with Breuer, Breuer had a general medical practice and lost interest in hysteria and didn't want anything to do with the revisions of Freud's work on hysteria. After that happened Freud, who was a very clumsy hypnotist by his own account, began to develop this alternative of free association and getting people to speak whatever came into their head without a censor. That was the important thing, that the half-murdered memories were being hidden from you and your—the constellation of psychological forces in your unconscious was squashing them down but they were reemerging as other kinds of symptoms.
One of the things after World War II when psychoanalysis was making great strides in America and the Rockefeller Foundation was still heavily involved in promoting psychiatry and developing what it hoped would be new tools in it—the then heads of the institute—of the funding program, Alan Gregg and Robert Morison, especially Morison, kept pressing the analysts: "Provide us proof that what you do works." And the analysts kept resisting and resisting and resisting, saying "It's much more complicated than that. There's no easy measure because what we're doing is reconstructing entire personalities, entire ways of being."
Another kind of psychotherapeutics is emerging in the aftermath, during and in the aftermath of the war as a rival for both psychiatry and for psychoanalysis. Initially not terribly successful, but as time goes on, a more and more important part of the story.
America's psychiatrists went to the military brass and to the politicians before America entered the war, and it had some advance warning because America didn't enter till Pearl Harbor, but the European war had been going on. And they said, "Look, if we have to fight, we're gonna have the same problem we had in the First World War. We're gonna train these soldiers, gonna equip them, we're gonna put them in the battlefield and the psychologically vulnerable among them are gonna break down. They'll be shell shock all over again, so we should screen all recruits to make sure they're not psychologically weak and susceptible."
And they screen out 1 3/4 million people and say, "These men are not fit. So now we won't have the problems we had in World War I." Except it quickly turns out that those problems reemerge. Industrial warfare exposes people to seeing things and doing things that all of us in normal life would recoil from. And when we're forced to do them as soldiers, many of them find the experiences and the memories those create intolerable. And they emerge in symptoms and they break down. So it became a huge problem for the American Army, as it did for all the armies. Actually, the Nazis just shot people. Broke down, bang, you're dead. We're not dealing with you. But obviously the Allies, that was not the response.
They quickly had to try to treat these troops, maybe get them back into the fighting lines, maybe get them into support positions. Something to cope with the problem, which was both created extraordinary morale problems among the troops and it invited malingering, claiming you had these conditions when you didn't. It obviously cost a lot of the fighting force. In combat conditions, as much as 25% of the soldiers broke down. So it was a big, big problem.
Before the war, there were about 2,000 psychiatrists in North America, in the US. At the end of the war, there were more than 2,000 psychiatrists in the US military. So you had to train people in a hurry, and even still, it was hard to get enough people trained.
After World War II, American psychiatry split into two distinct groups. William Menninger from the Menninger Clinic in Kansas became head of Army psychiatry. He concluded that the best treatment for soldiers breaking down was psychotherapeutic, with the origin of their condition being trauma. In a watered-down way, Freud's ideas were absorbed by people who were quickly recruited and retrained as psychiatrists. These formed a coherent group separate from the psychiatrists in state hospitals who remained biologically oriented.
Another group emerged during the war because there weren't enough MD psychotherapists being produced quickly enough. Psychologists were drafted in and asked to treat patients. They discovered they could do this work and found it interesting and challenging. After the war, psychiatrists moved to outpatient treatment rather than working in mental hospitals. By 1958, about 80% of psychiatrists were working in outpatient settings rather than hospitals.
The psychologists organized themselves and received federal funding from the Veterans Administration and later the National Institute of Mental Health for training. They developed a clinical training program where would-be clinical psychologists spent two years learning basic scientific psychology and research methods, followed by two or three years of clinical work. This gave them an advantage in applying for federal grants, while psychoanalysts had little experience with grant applications and received almost none.
Clinical psychologists focused on treating symptoms directly, while psychoanalysts viewed treating symptoms as playing Whac-A-Mole - if underlying personality problems weren't addressed, suppressed symptoms would reappear elsewhere. Clinical psychologists developed techniques like cognitive behavioral therapy and later interpersonal therapy that worked relatively quickly on specific problems. CBT helped patients identify patterns they'd fallen into and provided exercises for better coping mechanisms.
Unlike psychoanalysis, which required years of treatment and was difficult to measure, CBT could be packaged, reproduced, and tested for effectiveness. It had an evidentiary foundation that psychoanalysis lacked. CBT was shorter and reproducible, while psychoanalytic treatment was highly individualized with each patient presenting new complicated dynamics.
The key figures in developing cognitive behavioral therapy were Albert Bandura, Albert Ellis, and Aaron Beck. Aaron Beck, who went by Tim Beck and lived to at least 99 or 100, was particularly remarkable. He remained intellectually sharp into his later years, with videos showing him still speaking wisely at advanced age.
Aaron Beck made two important contributions. First, in the 1960s, he was one of the first to examine psychiatric diagnosis and demonstrate its unreliability - how difficult it was for psychiatrists to agree on diagnoses. This was crucial for the movement toward DSM-III. Second, he broke with the psychoanalytic view that treating symptoms was a waste of time and joined the psychologists developing symptom-focused techniques.
Interpersonal therapy, which emerged from this movement, focused on how relationship breakdowns damage emotional stability and how repairing relationships helps restore emotional stability. Americans were more willing to pay for clinical psychologists since the U.S. lacked socialized medicine. Clinical psychologists successfully treated problems of everyday living that were often quite distressing.
The evidence for CBT's effectiveness is mixed. Cochrane Reviews assessing evidence strength indicate that at best, the evidence for CBT is of low and medium confidence. The evidence is particularly poor for schizophrenia cases. For milder forms of depression, CBT appears to work better than drugs without the side effects associated with medication. NICE, the British organization evaluating treatments for the National Health Service, reached the same conclusion.
Before the mid-20th century, hardly anyone conceived that drugs could treat mental illness. Drugs had been used in mental hospitals in the 19th and 20th centuries, but primarily to control patients - opiates, hypnotics for agitation, and experiments with marijuana and alcohol. The idea that drugs might attack underlying problems emerged accidentally. The drug industry had emerged primarily in Germany from the chemical industry, including refining coal tar into substances like aspirin.
World War II accelerated drug development, particularly with penicillin's discovery. Alexander Fleming observed penicillin's antibacterial properties, but Howard Florey and his Oxford team developed its therapeutic potential. Florey flew penicillin across the Atlantic, and Americans solved the critical problem of mass production. After the war, drug companies grew wealthy from penicillin and began researching new therapeutic substances.
A French company, Rhône-Poulenc, discovered chlorpromazine, a chemical synthesized in Germany in the 1880s as an antihistamine. They sought various markets for it, including as an antiemetic for car sickness and for eczema. The drug investigation process was essentially unregulated - companies handed out substances and asked physicians to "try this and see if it works." One possibility explored was using it as an anesthetic potentiator since it tended to make people sleepy.
French Navy lieutenant Henri Laborit tried chlorpromazine as an anesthetic potentiator and gave it to surgical patients awaiting procedures. These patients stopped being anxious. Laborit wrote that it worked "like a chemical lobotomy" - patients didn't care about their surgery. A colleague contacted Delay and Deniker at Saint-Anne's, Paris's largest mental hospital, suggesting they try it on psychiatric patients.
When initial doses didn't work on psychiatric patients, larger doses were administered. Patients stopped acting out, stopped smashing furniture, became less mobile, and much calmer. Chlorpromazine became known as Largactil ("Mighty Drug") in Europe and Thorazine in America. Initially, it was called a "major tranquilizer" because of its tranquilizing effect, viewed primarily as a means to control patients rather than cure them.
Chlorpromazine came to North America via Quebec, where psychiatrist Heinz Lehmann worked at the Protestant Hospital. Because of the French connection, he obtained supplies of the drug. Rhône-Poulenc sold the American rights to SmithKline & French after two other drug companies declined, believing there wasn't much market potential. Within two years, two million people were taking the drug, transforming SmithKline & French from a small operator into a major company.
Drug companies realized hospital psychiatrists weren't initially interested in these drugs as treatments. Companies sold the concept to politicians and state legislatures using moving pictures showing agitated patients becoming calm. This represented the emerging mechanism of what would become "big pharma." Once chlorpromazine proved successful, it could be easily modified chemically, leading to copycat drugs.
In 1955, the so-called "minor tranquilizers" emerged with Miltown, heavily promoted by television star Milton Berle, who called himself "Uncle Miltown" and promoted the drug on his show. These were muscle relaxant types of drugs. In the 1960s, Valium and Librium were added to or replaced these first-generation drugs. Freudians wanted nothing to do with these medications, while hospital psychiatrists began using Thorazine and its analogues extensively.
In the early 1960s, major tranquilizers were renamed "antipsychotics," suggesting they attacked underlying psychosis. These drugs reduced agitation, delusions, and hallucinations - what psychiatrists called the "positive symptoms" of schizophrenia. The term "positive symptoms" refers to active phenomena like hallucinations and delusions, which are visible and activate behaviors, as opposed to "negative symptoms" like apathy, loss of social ability, poverty of language, and lack of initiative.
Antipsychotics work on positive symptoms for some patients but not others, and they don't address negative symptoms effectively. A significant number of psychotic patients are non-responders, just as many depressed patients don't respond to antidepressants. Initially, enthusiasm for these drugs led to neglect of their serious side effects, with some arguing side effects were essential to treatment.
Antipsychotics cause several serious side effects. Some patients become incurably restless, constantly moving and never still. Others develop Parkinson's disease symptoms. The most severe is tardive dyskinesia - late-developing jerky, uncontrolled movements, particularly of facial muscles, causing tongue protrusion, strange noises, twitching, and staggering. People exhibiting these symptoms are often recognized as mentally ill, though these are iatrogenic effects of the drugs themselves.
The tardive dyskinesia problem was ignored for about 20 years until psychiatrist George Crane published a paper in Science stating the profession had been ignoring this terrible problem. The drugs do good but also create harm. By the 1980s, the American Psychiatric Association became very worried about this issue.
Clozapine was developed in 1957 as a copycat version of Thorazine by a small company later bought by a larger one. It was introduced in Europe but never reached America for two reasons: it tended not to produce tardive dyskinesia, which many thought meant it wasn't attacking the problem, and it destroyed white blood cells in a significant number of patients, causing deaths. It was withdrawn from the market and never made it to America.
As the tardive dyskinesia problem became acute, clozapine was revived. It works better in treatment-resistant cases that don't respond to other antipsychotics. It could be used but required weekly blood checks to monitor white blood cell counts. It came to market in the late 1980s, and other drug companies quickly developed chemically unrelated compounds. This class became known as "second generation antipsychotics," including Clozaril, Risperdal, and Zyprexa.
Second-generation antipsychotics have different side effect profiles, slightly different modes of action, and varying efficacy levels because they're chemically quite different from each other. There was no established protocol for determining which drug to prescribe to which patient based on individual characteristics.
Once the drug revolution began, studies were increasingly funded by drug companies who owned and controlled the data, releasing only favorable results. Companies conducted many trials but needed only two successful ones for FDA approval of efficacy and safety. Even if 13 of 15 trials failed, two successful trials were sufficient.
In 2005, the National Institute of Mental Health funded the CATIE Study, published in the New England Journal of Medicine, comparing first-generation antipsychotics (now off-patent and cheap) with second-generation drugs (patented and expensive, up to ten times costlier). The study found that newer drugs were not more efficacious than older ones. Between 67% and 82% of patients dropped out because drugs weren't working or side effects were intolerable. This revealed real complications with even the best available drugs.
Second-generation antipsychotics produce less tardive dyskinesia but introduce new metabolic problems. Patients typically gain 10, 20, 30, 40, or 50 pounds, leading to metabolic syndrome, diabetes, and heart trouble. There is no free lunch with medicine. An aspirin may cause stomach bleeding severe enough to create serious jeopardy, though most of the time it is fine. Every drug brought to market has the main effect sought and some side effects that may be minimal for most people but worse for some. Treatment involves cost-benefit analysis. Patients receive relief from psychiatric symptoms while courting other dangers that may or may not arise. It is impossible to know where any individual will fall on the distribution curve. There are no biological markers currently available to predict outcomes.
Researchers in psychiatric genetics hope to distinguish which patients will respond well to drugs and which should avoid them due to lack of response or severe side effects. This remains a promissory note rather than current capability. Side effects vary, though much of the described effects are common to this class of drugs. Describing side effects involving the human mind is difficult. Weight gain is describable, but effects on personality are much harder. Some patients drop out because they find the richness of their mental life completely gone, preferring to tolerate hallucinations over this loss.
SSRIs including Prozac, Zoloft, and Paxil represent the second generation of antidepressants. Their development was accidental. In the 1950s, researchers treated advanced tuberculosis patients with new drugs. These patients, who were coughing their lungs out and severely depressed, began acting happy and dancing. Their mood changed. However, drug companies around 1960 viewed depression as a small market, referring to melancholic psychotic depressions requiring hospitalization. The market expanded later. Depression is now the common cold of psychiatry, the most commonly given diagnosis among psychiatrists. This expansion reflects both deeper understanding of the human mind and drug companies convincing the world.
DSM-5 deliberations included disputes about whether grief and bereavement would count as mental disorders or forms of depression. Diagnostic creep is a term coined by Australian Nick Haslam. The phenomenon begins with a core of unambiguous deviations from the norm so serious that any competent member of the culture recognizes them. Then a penumbra develops where people are disturbed but not sufficiently to be immediately recognized. Allen Frances, chief editor of DSM-IV, believes the huge increase in autism diagnoses resulted more from loosened criteria than from actual increase in cases. Autism was formerly rare and is now a very broad diagnosis. Parents resist narrowing the criteria because the diagnosis provides access to social and educational supports. There is a real difference between severe autism involving loss of speech and ability to interact and milder but still serious cases.
Diagnostic creep is not driven solely by psychiatric imperialism. It is also driven by patients and families. Family organizations like NAMI represent family members of the mentally ill, not the patients themselves, and there are differences in perspectives and interests between these groups.
Mental illness is the most solitary of afflictions for the sufferer and the most social of maladies for those around them, a paraphrase from historian Michael MacDonald. Effects extend beyond the individual to everyone around them. First-generation antidepressants included MAOIs and tricyclics, named for their three-ring molecular structure. These had limited markets and complications including easy overdose leading to death, making prescription to depressed patients risky. Certain dietary items like cheese and cured meats combined with these drugs could be fatal.
Late 1980s brought a new class of antidepressants without those particular side effects. Prozac was the most famous. SSRIs are selective serotonin reuptake inhibitors. Serotonin is manufactured in the digestive system and functions as a neurotransmitter in the brain. These drugs slow serotonin reuptake and were marketed as solving depression caused by insufficient serotonin. Tipper Gore, Al Gore's ex-wife, became a public advocate for SSRIs, which remain the most prescribed antidepressants.
Controlled studies show antidepressants beat placebo with statistical significance but not necessarily clinical significance. Drug advertisements claiming significant improvement require careful interpretation. Improvement measured on rating scales may show statistical significance with one or two points on a 60-point scale, but this may not affect quality of life substantially. For most patients, antidepressants are marginally better than placebo, with much of the effect being placebo effect.
Side effects include flattening of experience, numbing that prevents experiencing normal highs and lows. Loss of libido is common, with inability to achieve erection or climax, sometimes persisting after stopping the drugs. Withdrawal can be severe, with worse depression than before and feelings of brain sparking. Many patients become trapped on these drugs long-term, with unknown long-term effects.
NICE in England recommends CBT as first-line treatment over drugs. Response patterns divide into three groups. One group responds well with bearable or absent side effects. A significant group, 40 percent or more of depressed patients, does not respond at all while running risks from the drugs. A middle group experiences some improvement alongside side effects, where cost-benefit analysis becomes difficult. It is impossible to predict which group any individual will fall into, and primary care physicians rather than psychiatrists now prescribe many antidepressants.
Patients suffering intensely from psychosis or depression probably need to try drugs while maintaining awareness and careful clinical monitoring. Psychiatric research needs to broaden beyond drugs, neuroscience, and genetics. Psychosocial dimensions of mental illness deserve attention, allowing psychiatrists to build careers in these fields. Academic psychiatrists depend on grant funding, which is unavailable for studying better ways to address homelessness or support families coping with hallucinations.
Psychoanalysis has become a niche product affordable only to the wealthy. AI systems capable of communicating with humans, learning about them, and discussing deepest secrets may mechanize aspects of therapy, potentially returning to realms Freud and Jung explored. COVID isolation accelerated distant therapy delivery. Psychiatrists need to broaden perspectives on these approaches. Public policy regarding serious mental illness is problematic, though fixing it would require substantial funding. Social interaction is tremendously important to mental health. Loneliness and isolation cause harm. Providing social support and sense of agency would be helpful. Major drug companies have abandoned research in this area despite some positive drug effects.
The profession contains many well-meaning people who see suffering daily. Highly motivated people have done good things to help those with these conditions. Progress requires shifting professional mentality toward more caring and less technocratic approaches, reducing reliance on pills alone. The system needs awareness of and response to patient suffering, finding ways to ameliorate it when elimination is not possible. Mental illness touches profound aspects of human existence. Cynicism should be avoided. Hope should not be abandoned. Possibility of progress should not be denied. Progress has occurred and may accelerate.
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