Scull Faults Decades of Psychiatric Drug Push as Jails Replace Asylums

斯卡尔批评数十年来精神药物推广：监狱沦为精神病院替代品 现代精神病学的生物还原论及对掩饰症状药物的依赖未能带来根治性突破，导致严重精神疾病患者从州立精神病院转移至地方监狱。 历史学家安德鲁·斯卡尔（Andrew Scull）梳理了精神病学的演变历程：从19世纪拥挤的收容性精神病院和激进的躯体实验（如局灶性感染切除手术、疟疾发热疗法和经眶脑白质切除术），到20世纪精神分析学与精神药理学的兴起。对话深入剖析了DSM系统如何用缺乏生物学有效性但具信度的症状清单取代精神分析的教条主义，最终助长了诊断泛化以及大型制药公司的营销。斯卡尔详细说明了战后“去机构化”运动如何导致严重的悲剧性二次监禁（流入地方监狱）与无家可归，而当代的抗精神病药物和SSRIs仍属于对症治疗，且常伴随严重的医源性伤害。在整个讨论中，斯卡尔呼吁采取综合且人道的方案，摒弃还原论式的生物医学炒作，在审慎的药物治疗、谈话疗法与至关重要的心理社会支持之间寻求平衡。 现代精神类药物的突破源自意外的偶然发现而非理性设计，该领域目前仍缺乏可与青霉素相媲美的根治性疗法。 (0:00) DSM-III引入的操作化症状清单为医保计费和药物试验提供了诊断信度，却未能提供生物学有效性，产生了将不同病理混为一谈的“发热谬误”。 (5:14) 尽管在“脑的十年”期间向遗传学和神经生物学投入了数十亿美元，NIMH前所长Thomas Insel仍承认，严重精神疾病患者的实际境遇丝毫没有改善。 (9:56) 精神病学从20世纪初忽视神经生物学的“无脑”精神分析，倒向了漠视切身经历与社会背景的现代“无心”生物还原论。 (15:00) 缺乏充分社区配套设施的“去机构化”导致了全国性的二次监禁危机，使Rikers Island和Cook County Jail等地方监狱沦为美国事实上的最大精神病医疗机构。 (25:00)

Historian of psychiatry Andrew Scull argues that the profession has repeatedly overstated its therapeutic triumphs, oscillating between psychoanalytic dogmas and biological reductionism while failing to uncover the biological validity of its core diagnostic labels or provide reliable cures. Diagnostic Checklists and the Elusive Biological Substrate (5:14) Modern psychiatric nosology underwent a radical shift in 1980 with the publication of the DSM-III, which abandoned Freudian psychodynamic theory in favor of atheoretical, symptom-based checklists. While spearheaded by Robert Spitzer to ensure inter-rater reliability, Scull emphasizes that reliability did not produce biological validity; psychiatric categories remain descriptive constructs analogous to 18th-century classifications of 'fever.' Former National Institute of Mental Health (NIMH) directors Steven Hyman and Thomas Insel eventually conceded that decades of neuroscience research failed to map these diagnostic silos to discrete biomarkers. Recent genetic research has further unsettled conventional nosology. Genome-wide association studies (GWAS) show that more than 300 minute genetic loci account for only about 10% of schizophrenia vulnerability, with the same markers appearing in bipolar disorder and autism. British psychiatrist Sir Robin Murray and other specialists increasingly view schizophrenia not as a discrete disease entity, but as the extreme end of a continuous spectrum. Concurrently, psychologist Nick Haslam's concept of 'diagnostic creep' explains how conditions like major depression have expanded outward—such as the DSM-5's elimination of the bereavement exclusion—medicalizing ordinary grief into treatable pathology. Desperate Remedies and Inpatient Somatic Experimentation (45:00) Throughout the early-to-mid 20th century, state asylums were overwhelmed by chronic, incurable cases, trapping superintendents in an arithmetic reality where discharge rates hovered at only 35% to 40%. Desperate to escape the role of mere custodial housekeepers and inspired by germ theory's triumphs in linking general paralysis of the insane to syphilis, alienists turned to hazardous somatic interventions on captive institutional populations. These experiments included Henry Cotton's surgical removal of teeth, tonsils, and colons to treat 'focal sepsis,' Julius Wagner-Jauregg's Nobel-winning malarial fever therapy, and Manfred Sakel's insulin coma therapy. In 1935, António Egas Moniz developed the prefrontal lobotomy, which Walter Freeman radicalized into the transorbital 'ice pick' lobotomy, severing frontal white matter in thousands of institutionalized patients and frequently leaving them functionally vegetative. While chemical convulsants like Metrazol caused severe bone fractures and terror, Ugo Cerletti and Lucio Bini introduced electroconvulsive therapy (ECT) in 1938. Though modern modified ECT using anesthesia and paralytics remains an evidence-backed intervention for treatment-resistant melancholia, early unmodified ECT was widely weaponized in state wards as an instrument of punitive behavioral control. The Psychoanalytic Ascent and Behavioral Alternatives (128:44) Outside asylum walls, psychoanalysis established early cultural and clinical influence. Sigmund Freud and Carl Jung introduced their framework to the United States during the 1909 Clark University conference. Although initially greeted with skepticism by American intellectuals like William James, psychoanalysis gained rapid medical traction when World War I 'shell shock' proved that catastrophic functional breakdowns could stem from psychological trauma without mechanical brain injuries. Jung subsequently cultivated wealthy American dynastic patrons, including the McCormicks, while European analysts fleeing Nazism entrenched the discipline in independent postwar institutes. By the late 1950s, outpatient psychiatry had expanded dramatically, but psychoanalysis faced structural challenges due to its rejection of empirical outcome metrics. Academic clinical psychologists—bolstered by post-WWII federal funding from the Veterans Administration and NIMH—designed rigorous research methodologies that outperformed psychoanalysts in grant competitions. Former psychoanalyst Aaron Beck broke from analytic orthodoxy over its diagnostic unreliability and dismissal of symptom treatment, partnering with behavioral researchers to develop Cognitive Behavioral Therapy (CBT), which targeted distorted conscious cognitions directly. Psychopharmacological Stagnation and the Transcarceration Crisis (25:00) Modern psychopharmacology began not through rational drug design, but through serendipitous industrial accidents in the 1950s, beginning with the phenothiazine antihistamine chlorpromazine (Thorazine) and the tuberculosis drug iproniazid. Initially labeled 'major tranquilizers,' first-generation drugs were rebranded as 'antipsychotics' to imply disease-modifying action, though they primarily suppressed florid positive symptoms like hallucinations while leaving negative functional deficits untouched. Early phenothiazines also induced severe neurological harm, including akathisia and irreversible tardive dyskinesia, while second-generation atypical antipsychotics introduced profound metabolic risks. Evaluating mood medications, Scull points out that clinical trials of SSRIs routinely demonstrate statistical significance over placebo by small numerical margins on rating scales without delivering clear clinical significance. Literature synthesized across psychiatric research indicates a tripartite response: a minority experience robust improvement, over 40% fail to respond entirely, and a large middle cohort achieves partial symptom reduction burdened by adverse effects. Compounding this stagnation, major pharmaceutical firms have largely exited psychiatric R&D due to scientific dead ends. Combined with mid-century deinstitutionalization lacking community support, patients with severe psychiatric illnesses now experience widespread transcarceration across jails and urban homelessness, facing lifespans shortened by 15 to 25 years. Scull concludes that reforming mental health care requires dismantling academic psychiatry's disproportionate funding focus on genetics and neuroimaging, which has starved community infrastructure and psychosocial support. Hope rests not in technocratic pharmacological panaceas, but in supporting dedicated frontline clinicians and constructing compassionate social systems that address the lived reality of psychological suffering.

精神病学历史学家安德鲁·斯卡尔（Andrew Scull）指出，现代精神病学在过去一个多世纪中屡次陷入从“无脑”的精神分析走向“无心”的生物学还原论的极端循环；该学科虽极力标榜科学权威与突破性疗法，但其诊断体系仍缺乏生物学有效性，临床实践也长期受制于偶然发现与过度商业化的药物干预。 诊断信度与效度的脱节及还原论局限 (5:14) 精神病学的分类体系在1980年《精神疾病诊断与统计手册》第三版（DSM-III）发布后经历了一场范式革命。为了摆脱主观臆断与诊断不一致的混乱，该手册抛弃了弗洛伊德式的病因假说，转向标准化的“症状清单”。然而，斯卡尔指出，这种转变虽然大幅提高了医生之间的“诊断信度”（一致性），却未能确立疾病实体的“生物学效度”。当下的核心诊断标签（如精神分裂症、重度抑郁症）更类似于18世纪医学中的“发烧”概念——它描述了一组共同聚集的临床症状，而非具有明确生物靶点的离散自然疾病。现代神经科学与基因组学亦未能证实传统疾病分类的生物学边界。全基因组关联分析（GWAS）显示，300多个细微基因突变聚集在一起仅能解释约10%的精神分裂症易感性，且相同的遗传变异广泛跨越精神分裂症、双相情感障碍和自闭症谱系。英国学者罗宾·默里（Robin Murray）等人因此认为，精神分裂症更可能是连续谱系上的极端精神病态反应。斯卡尔强调，将复杂的人类心智硬性割裂为生物大脑与社会环境是根本性的范畴错误，人类大脑具备高度可塑性，社会压力与生活经验早已在物理层面深刻嵌入神经结构中。 收容所危机与激进躯体干预的惨痛代价 (45:00) 19世纪建立的公立精神病院曾声称享有70%至80%的治愈率，但实际出院率仅在35%至40%徘徊。每年无法出院的慢性病患迅速累积，形成了收容所危机。不愿沦为看管性“高级看门人”的医生们，在缺乏有效手段的绝望中走向了激进粗暴的躯体实验。加之神经梅毒引起的“麻痹性痴呆”被证实源于感染，并促成瓦格纳-尧雷格（Julius Wagner-Jauregg）因疟疾发热疗法荣获诺贝尔奖，医学界遂深信破坏性生物手段能够逆转所有精神错乱。在这一逻辑下，20世纪上半叶充斥着骇人听闻的临床介入：亨利·科顿（Henry Cotton）坚信“局部感染病灶”理论，大规模拔除病患牙齿并切除内脏；曼弗雷德·萨克尔（Manfred Sakel）使用超量胰岛素诱发昏迷；拉迪斯拉斯·梅杜纳（Ladislas Meduna）注射美曲唑引发剧烈抽搐致使患者脊柱骨折；乌戈·切尔莱蒂（Ugo Cerletti）等人随后发明了电休克疗法（ECT）。最臭名昭著的是安东尼奥·埃加斯·莫尼斯（António Egas Moniz）开创并获诺贝尔奖的脑白质切除术，该手术被沃尔特·弗里曼（Walter Freeman）推行为流水线式的“冰锥”眼眶手术，导致数万名病患沦为丧失认知能力的“植物人”。这些极端实验反映了当机构权力、狂热假设与缺乏对照的临床环境结合时所催生的灾难。 精神分析的神话破灭与认知行为疗法 (131:58) 20世纪初，弗洛伊德开创的精神分析学说作为对收容所机械生物论的反拨而崛起。1909年弗洛伊德与荣格赴克拉克大学演讲，并在第一次世界大战后因解释“炮震”（shell shock）等非器质性创伤而风靡欧美文化界。然而，斯卡尔分析道，经典精神分析极度依赖高昂且漫长的个别谈话，内部宗派林立且抗拒实证检验，逐渐退化为封闭的教条体系；弗洛伊德严厉清洗异见者，而荣格则依靠吸引埃迪思·洛克菲勒·麦考密克（Edith Rockefeller McCormick）等超级富豪的赞助建立了独立的分析流派。二战后，美国退伍军人事务部（VA）与国家精神卫生研究所（NIMH）向临床心理学注入巨资，推动建立了结合实验研究与临床技能的培训体系。曾受正统精神分析训练的阿伦·贝克（Aaron Beck）因目睹精神分析诊断的极低信度与理论僵化，打破了“干预表层症状毫无意义”的弗洛伊德式信条，率先推动诊断标准化，并结合行为主义技术开创了认知行为疗法（CBT）。这一转向使心理干预逐步摆脱了精神分析的形而上学特质，建立在结构化、短程且可实证检验的现代临床框架之上。 药物革命的偶然性、商业化与疗效局限 (170:00) 20世纪50年代拉开序幕的精神药理学革命并非源于理性靶向研发，而是染料和抗生素工业发展中的意外产物。第一代抗精神病药氯丙嗪（Thorazine）最初作为合成抗组织胺衍生物被引入，而最早的抗抑郁药异烟酰异丙肼则是治疗晚期结核病时的副反应产物。尽管药物促成了去机构化运动并取代了外科手术，但第一代抗精神病药带来了严重的迟发性运动障碍、静坐不能等神经损伤；第二代非典型药物虽减少了运动障碍，却引发了严重的代谢紊乱与体重激增。前NIMH主任史蒂文·海曼（Steven Hyman）承认，经历数十年研发后，当代药物在疗效上相较于50年代化合物并未实现根本性跃升。跨国药企随后推动了抑郁症等范畴的“诊断泛化”（diagnostic creep），甚至在DSM-5中删除了丧亲哀恸排除标准，将正常的日常痛苦广泛医疗化。双盲试验表明，选择性5-羟色胺再摄取抑制剂（SSRI）的统计学显著性往往被营销夸大为临床显著性，绝大部分疗效被安慰剂效应所占据，且伴随强烈的情感迟钝与停药综合征。《柳叶刀》等发表的研究表明，抗抑郁药仅对少数患者有稳健疗效，超过40%的患者完全无反应，其余群体则承受严重副作用。面对靶点匮乏与巨额诉讼，主流药企已大举削减严重精神障碍研发，而缺乏社区照护支持的去机构化政策更是导致大量病患陷入在流浪与监禁之间徘徊的“转序监禁”（transcarceration）困境。 斯卡尔总结认为，现代精神病学的出路在于打破学术界对脑成像、分子遗传学和专利药物试验的垄断性资助偏见，纠正“只要给一片药就能解决一切问题”的技术官僚幻想。由于人类精神体验与社会关系密不可分，未来的希望取决于重建兼顾心理社会支持与社区照护的综合干预体系，并保持临床从业者直面人类苦难的人道同理心与科学谦逊。

[9:56] Thomas Insel: lot of the mentally ill improved not one bit [15:00] Leon Eisenberg: When I entered psychiatry, it was a brainless psychiatry. And when I'm leaving it, it's a mindless psychiatry. [30:00] Andrew Scull: a shell game without a pea [50:23] Walter Freeman: could teach any damn fool to perform a lobotomy in 20 minutes, even a psychiatrist. [75:00] Manfred Sakel: killing the schizophrenic brain cells [80:00] Not another one, it's deadly! [95:00] Andrew Scull: I see ketamine and psychedelics being propounded as a miracle cure for depression. And the evidence for that is enormously weak, is the best way to put it. And I've seen this movie before too many times. You know, I mentioned that 80% cure for Cotton's work, 80% cure for insulin coma therapy, 80% cure for the early asylums. This is overblown rhetoric, and the reality is usually progress comes in small steps. [139:48] Sigmund Freud: grotesque unhappiness into ordinary unhappiness [160:00] Andrew Scull: The psychoanalysts think to treat a symptom is to play whack-a-mole. If you don't deal with the underlying problems of the personality, the interaction between your id, ego, and superego, you suppress that symptom and another one will pop up over here. The clinical psychologists go, we're going to treat the symptoms of what are troubling people. We're going to treat the symptoms and we're going to develop techniques that allow people to cope with those symptoms and eliminate them. [195:00] Michael MacDonald: the most solitary of afflictions for the sufferer [215:00] Friedrich Nietzsche: To live is to suffer. To survive is to find meaning in the suffering.

[0:00] The following is a conversation with Andrew Skull, a historian of psychiatry and mental health. He has authored many books that I highly recommend, 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. Andrew Skull has spent decades studying how societies have understood madness, how psychiatry rose to authority, and how often that authority was used with false confidence and catastrophic consequences. In this conversation, we'll trace the long arc from the asylum era to eugenics, from lobotomy and insulin coma therapy to electroconvulsive therapy, psychoanalysis, antipsychotics, antidepressants, and the modern crisis of mental health. It is, in part, a story about the terrifying history of bad ideas in medicine, but it is also about the fascinating mystery of the human mind and about the difficult journey to understand it. This is a Lex Ruminant podcast. To support it, please check out our sponsors in the description, where you can also find links to contact me, ask questions, give feedback, and so on. Right now, dear friends, here's Andrew. Skal. Is it fair to characterize your view on psychiatry and mental illness is that there's a crisis in modern psychiatry? We have made some progress over the past century, but mostly we still are not good at treating mental illness either via the drugs or talk therapy, meaning psychopharmacology or psychotherapy, or as you put it, the brain or the mind route. story. Let's start at where we stand before we go into the rich history that you so eloquently write about. So psychiatry is a profession that tries to deal with an enormously complicated thing. the human mind, the human emotions, the human ability to attempt to understand the world. And in particular, obviously, it focuses on people where our common sense approach to the world seems to break down. People whose emotional life is filled with turmoil, people whose ability that the rest of us simply think are there. They're illusions, they're hallucinations, they're delusions. And this is a subject that has occupied some very clever minds over the years. And there's no question that in the course of at least the last three quarters of a century, creates. Some of that is confined to the milder forms of mental distress, the more serious forms of psychosis and breakdown of emotional control. Those are areas where I think, again, there's been some progress, but it's easy to overstate how much of that there's been. As we'll see probably later in our conversation today, the advent of modern psychopharmacology, which occurred in the early 1950s, was a serendipitous event. It wasn't planned for, it happened previously. almost by accident. And it did mark, in some ways, an advance over some of the things that psychiatry had engaged in before that. And no question for some people, that revolution and a parallel revolution in the psychotherapeutic realm have created some advance for patients and we should not minimize that. What we have available to us are symptomatic treatments, not cures. We don't have a psychiatric penicillin for any of the conditions we're going to be talking about. That doesn't mean we can't do some things that help, but the help is quite limited. And it's important to understand both the ways in which we have progressed and We create new problems, what we call iatrogenic problems, things caused by the interventions that we use. That's true of some psychotherapeutic interventions, and it's most certainly true of the drugs we use to treat mental illness these days. [5:00] or in treating PTSD, we often get patients to confront the episode, the trauma, which provoked their distress. And that is often a very, very fraught process. And for many patients, it actually makes things worse. For some patients, it makes them better. So, that's a situation where you can see problems. With both antipsychotics and antidepressants, the two main classes of psychotropic drugs that we use, There are They're at best partially effective, and they don't work for a significant fraction of patients who are given them. And one of the big problems psychiatry faces is that Psychiatrists don't know in advance who's going to respond well to the drugs, who's going to respond badly. For which group of patients in the middle, the side effects and the main effects, if that's what we want to call them, the therapeutic effects, are finally balanced and making those judgment calls about what to do. is very, very difficult. Now, in terms of the crisis psychiatry faces at the moment as I see it, There are a number of strands that point to this. Psychiatry's diagnostic system that is still used, I mean, the fundamental basis of psychiatric diagnosis today was really first formulated in 1980 with the, third edition of the Diagnostic and Statistical Manual of the Profession. DSM-3. DSM-3, and then there's been DSM-3R, DSM-4, DSM-4TR, and now DSM-5, finally not with a Roman numeral, but with an Arabic numeral. So they thought with DSM-5, when they needed to modify it, it would be like a piece of software. You have Windows 10, Windows 11, and so on, right? Now, that diagnostic system came into being because psychiatrists had a very hard time agreeing with one another about what was wrong with somebody. And that became embarrassingly clear, first in the professional literature, which outsiders didn't read, and then via a very famous study that's a scientific fraud by David Rosenhorn called On Being Sane in Insane Places, where he claimed to have sent in pseudo-patients And they all were diagnosed as schizophrenic. The other is somebody with bipolar disorder. And they were fake patients. So almost in a panic after that study appeared in science. And because there was an abundant professional literature from the 1960s showing the same thing, that diagnosis was a very erratic process. was explicitly set up to try to create a sort of tick-the-boxes approach to deciding which box a patient belonged in. Were you schizophrenic? Were you this type of schizophrenic or that type of schizophrenic? Were you manic-depressive or bipolar? Did you have various forms of depression? And to construct those boxes, what they relied upon was a list of symptoms. And if you had more than a certain number, if you had more than six or ten or more symptoms of a certain sort, You could be diagnosed with major depression, for example. So that system came into being. It was partially embedded because it appealed to drug companies who were developing drugs to treat these various disorders. It appealed to insurance companies because it gave them a stable basis to look at. It appealed. appealed, as diagnosis always does, to patients and their families who are scrambling to deal with these enormous upsets in the mental life of either themselves or a family member. So it provided some sense of certainty around diagnosis. kind of, fever for example, well fever and other diseases they talked about in the 18th century are really a constellation of very different things under one label. And I think that's what is turning out to be true of the DSM [10:00] labels. But that approach was really all that psychiatry could come up with if it wanted to make sure, whether you were in Walla Walla or New York or San Francisco or Atlanta, you reached the same conclusion faced by the same patient, that you had a reliable diagnostic system. That didn't mean necessarily it was a valid diagnostic system, if you understand the means you and I faced with the same sets of facts reach the same conclusion, but that conclusion may or may not reflect the underlying reality of things, right? So you had this diagnostic system and it went through various... iterations, each time it went through an iteration, the number of possible psychiatric disorders you could get grew and grew and grew and it became difficult to believe in some of those categories shall we say that they were really illnesses rather than and then some sort of social construct but beyond that um Psychiatrists wanted to be more like other medical doctors. Doctors, to root... their diagnoses in an understanding of the underlying pathology of the disorder? What was it that cause people to become schizophrenic. The sense was, if we could grasp that, we'd have a better handle on how to attack it, how to treat it. And when DSM-5 was mooted. the fifth edition in the early 2000s. NIMH, then under the leadership of Stephen Hyman, who's at Harvard now, and succeeded by Thomas Insel, who ruled NIMH for about 13 years, the two of them had pushed psychiatry and psychiatric research in a very particular direction. On the one hand, towards understanding the genetics of mental illness, and and on the other to looking at what the new discipline of neuroscience could contribute to understanding things. Both of them were heavily invested in the idea that mental illness was brain disease, And if it was brain disease, then the question was, what was making the mechanism here go awry? What was... causing people's emotions or their cognitive skills or their sense of the world to become so you disordered. They invested a lot of money in that approach. When Ensel stepped down, he gave an interview actually to somebody at MIT, and he's repeated it since in a book he wrote about his experiences, where he said, well, you know, as I look back on my 13 years, I funded an enormous amount of scientific, really cool scientific research. I funded geneticists, and I funded And after spending $20 billion, the lot of the mentally ill has improved not one bit. Which was a pretty devastating statement, I thought. And IMH is National Institute of Mental Health. National Institute of Mental Health. Yes, I shouldn't resort to jargon. But the National Institute of Mental Health had been founded in the late 1940s with the goal of improving, doing basic research, training people in the field, advancing the care of the mentally ill and producing, obviously, cures and advances. Its mission has varied widely over the years since, but it's... Starting in the 1990s, the period when the first George Bush declared the decade of the brain, NIMH increasingly focused on the idea that mental health was purely a brain disease. And there's something to that. And there's also a mistake in thinking about it that way. This is, by the way, as we'll talk about, this distinction between seeing mental health, the maladies of the human mind as a problem of the cognitive science, psychotherapy, these more, less amenable to scientific rigor. So I think what's appealing about the studying the brain and neurobiology and neuroscience is there's data. Yes. It's more rigorous. You could do science. It's the kind of thing that really appealed to medical school deans. Because once NIMH and the drug companies too were funding basic research on neurobiology and basic research [15:00] on genetics. The money's flooded in. And psychiatry, which had been something of an orphan, became much more popular. And we should say that this is something you write a lot about, that there's all these factors to consider. So there's the cultural elements. There's the political public policy elements. And there's, at a certain point, the drug companies and the insurance companies come in. And there's, of course, all the human beings around somebody who is suffering with a mental health issue. So the family factors, and that's connected to the cultural stuff. It's a very, very complicated area, and oversimplification is a real problem, I think. And I think even that dichotomy you just drew between... The brain... and the social or the psychological or some mix of those things. I think in some ways that's a category mistake. That's a mistaken way of looking at the world because the brain you and I have today is not the brain we were born with. Human brains are remarkably plastic things. They develop in response to the environment. So the social and the psychological end up being embedded of saying one or the other. No, there's abundant evidence from epidemiology that social factors play an important role in the development of mental illness. Nevertheless, the history of psychotherapy, for example, but all of these subfields, the human mind is incredibly complicated with all of these factors. So in order to say anything lot towards a very particular view of the human mind. And that, you know, that simplification is actually, I mean, we'll talk about it, but it's not correct to do in some deeper sense, but it also can be productive. Yes. In fact, I, Whenever you're trying to deal with a very complicated situation, set of issues. You have to simplify, you have to make heuristic decisions about what you're going to neglect and what you're going to emphasize. But what I'm trying to say, will you ask me about the crisis in psychiatry? And The simplest way for me to encapsulate the issue and the problem as I see it that's arisen, one of the problems, is a quote by Leon Eisenberg, who had a very long career at Harvard. Eisenberg, said towards the end of his career, he said, when I entered psychiatry, it was a brainless psychiatry. And when I'm leaving it, it's a mindless psychiatry. And I'm, I think that sums up the way in which it the field has to a large degree moved. And I think in the process, Important insights have been lost, even though in some ways other things are being gained. Freudians tended to neglect the biological, to suggest the brain That's it. biological organism was not something we needed to worry about. We worried at the level of a psychological model of how our minds work. And All too often, Not exclusively because some of the psychiatrists I'm friends with are very sophisticated men and women and do grasp that you can't. move in these bipolar directions. You've got to meet somewhere in the middle. But that sort of got lost, I think, in all the enthusiasm for neuroscience. I mean, when antipsychotic drugs were discovered in the And one of the things that... they helped to spawn as people began to say, well, why do these drugs work? What do they do? Was to begin to understand that the brain wasn't just a set of electrical signals, as had been thought in the first half of the 20th century and before, but rather there was this very interesting chemical soup running around in our brains with neurotransmitters that helped the it was one of the many factors that gave rise to neuroscience. The first neuroscience conventions were in the 1970s. They attracted a few hundred people. Now it's tens of thousands of neuroscientists. It's a huge enterprise. So diagnosis has come under threat. The categories that we have all [20:00] become familiar with, that we're told are real diseases like bipolar disorder, schizophrenia, major depression. Thank you. are... beginning to falter. We're beginning to worry about whether those diagnoses are real ways of thinking about the world and may in fact mislead us. Because if we think there's something called schizophrenia, or the schizophrenia, as the inventor of that term put it, if we think there's something like that, and we try to research where it comes from. But that's not really what's going on. Obviously, we're probably going to, not make the progress we could be making if we had a better diagnostic system. And that's what DSM-5 thought it was going to be able to do and discovered it couldn't. So it stayed basically with this symptomatic approach. If we can, just really brief, I would love to talk a little bit more about the DSM, but just to give history here, looking it up on perplexity, DSM-1 in 1952 was a 32-page pamphlet with 106 diagnoses heavily influenced by psychodynamic concepts and etiology in 1968 expanded to 185 diagnosis still psychodynamically flavored and reliability poor but added more attention to childhood disorders and later removed homosexuality as a disorder in 1974 printing then to the revolution as you mentioned the dsm-3 in 1980 introduced explicit symptom-based diagnostic criteria a multi-axial assessment system and an officially a theoretical stance about causes aiming to improve reliability and research utility. And then DSM-3R in 1987, revised criteria and expanded to around 297 diagnosis. DSM-4 in 94 and DSM-4TR in 2000 focused on literature-driven empirical revisions, added and deleted some Thank you. 2013, DSM-5 came out, which eliminated the multi-axial system, integrated most information into a single non-axial diagnostic list and separate notations for psychological and medical factors. It reorganized chapters, e.g. neurodevelopmental, obsessive-compulsive-related, trauma and stress-related disorders, introduced new and refined entities, and so on. Conceptually, the DSM moved from cause-focused and psychoanalytical to symptom-based, atheoretical, and reliability-driven. Over time, there has been growth in the number of granularity of categories, closer alignment with ICD, ongoing controversy over medicalization validity and the balance between categorical and dimensional approaches. Yes. It feels like that description doesn't. necessarily fully get to the core of why the gsm-5 doesn't quite get the full scope of the problem you invest a ton of money you invest yeah 20 billion more than 20 billion dollars in a particular approach and at the time you're constructing this you say finally you're because of all the work that's been done in genetics, we now have decoded the human genome. We have PCR so we can chop it up and we can look at bits of it. We have a lot more understanding of the role of neurotransmission in the brain. Surely we're going to be able to recast our diagnostic system based on underlying pathology so that we won't be worrying about symptoms anymore. We'll be looking at the actual underlying pathological changes that have taken place. But in the event, it turned out they couldn't do that. By about 2008, they'd thrown up their hands and said, no, we're going to have to continue to refine but rely upon the same basic approach that we developed in 1980. and When that document came out, and there'd been a lot of criticism, some of it from Robert Spitzer, who had been largely in control of DSM-3 and DSM-3R, and then his successor, Alan Francis, who'd run DSM-4. They both were fiercely critical about what was going on and said it was being done in the dark, and it was done in secrecy, and it wasn't scientific. And when it was about [25:00] to come out. Thomas Insull and Stephen Hyman, the two then existing and the preceding director of the National Institute of Mental Health, denounced the document as a. unscientific and useless. So if you're talking about a crisis, that's a crisis for the field. If its diagnostic system is being dissed by leading figures like that. What else was a problem? The difficulties with the drug existing therapies that particularly had become more and more manifest. And to make matters worse, Partly because... Big Pharma had sometimes behaved, shall we say, rather unethically with these drugs. It had hidden things that undercut their claims. It had manufactured studies. It had manipulated data. And it got caught out, and it paid billions of dollars in damages for some of the tricks that it got up to. Not just in psychiatry. for example, the painkiller, was another huge scandal. It was a $5 billion settlement. But the drug companies, had suffered some reputational damage. Beyond that, they didn't have any real clues. Unfortunately, neuroscience hadn't thrown up new targets for different forms of drug development. They decided they could make more money with spending their money on research. on other diseases and not mental illness. A crisis was you were stuck with a set of drugs that Steve Hyman says aren't really any advance on the ones that, by accident, we found in the 50s. And there isn't new research, unless it's small startups going on, to develop new ones. So you have an increasing sense your diagnostic process is falling apart. your Drug treatments' limitations are becoming more manifest. and as well as you for people with serious mental illness, public policy has screwed things up badly. So if you are a person with serious mental illness, you will die on average 15 to 25 years before the rest of us. And that gap has been growing rather than diminishing. So that's not a good thing. It's not something I want to lay entirely at the door of psychiatry. So don't get me wrong. I think a lot of this is public policy that has really abandoned, um, treatment for the seriously mentally ill. And you see it on the streets of our cities. You see the sidewalk psychotics. You see people who are cycling between brief periods of inpatient care, the gutter or the flop house, and the jail. So the three largest centers of inpatient psychiatric care, if you can call it that in the United States today, are the Los Angeles County Jail, and Rikers Island in New York. That's shocking. because by their very nature, of course, prisons aren't equipped to deal with serious mental illness. So some dark ways to return to the asylum era. Yeah, well, you know, the asylums had acquired a very bad reputation, and I've written about some of the reasons why that happened. But when asylums were founded, it was a period of enormous optimism that we were going to be able to cure these people, and from jail cells, and providing a therapeutic environment, coaxing them to work, creating a system where they learn to control themselves, not necessarily to drive their demons out, but to keep them under some sort of wraps. The expectation was, when the asylums came along, that they'd not only rescue people from horrendous conditions in the prisons and the jails, but they'd actively cure earliest alienists, as they called themselves then, thought that they could cure a 60, 70, 80 percent, maybe even more, of patients as long as they came in early. And really asylums were built out of that sense of optimism, that sense that so much was environmental and so much was not exacerbating the condition by treating people like animals or treating them, you know, beating them and in other ways horrifically maltreating them, that that would create a [30:00] and secure. Really, that underlay the construction of the asylums. Now, having abandoned the asylums, which we did starting a little bit in the 1950s, but really the late 1960s onwards, that was because there was going to be something miraculous called community care. But community care is a shell game without a P. It's like one of those confidence tricks. There were no substitute community facilities for dealing with the really serious mentally ill. So now we're in this truly, in this crisis, in this essentially dark ages, and in part I think our conversation, our journey through the history of psychiatry. is an exploration of some gigantic mistakes, but also an exploration of where lay some hope for the future. So we'll talk quite a bit about this. I was wondering if you can also just lay out what are the big categories of mental illness that we're referring to. You've already hinted at them, but like levels of seriousness and the categories of illness, like with psychosis and depression and so on. So going back to the early 20th century, was when the German psychiatrist, Emil Kreplin, working with thousands of records in German asylums, inductively developed a distinction between two very broad categories of mental illness. One he called dementia praecox, or early dementia, and the other he called manic depressive illness, which was a more remitting illness Other times went back and forth, whereas dementia praecox was a one-way ticket down. Now, that label was transformed by a Swiss psychiatrist, Edith. into the term we use today, schizophrenia, although Broiler talked about the schizophrenia because he thought under that broad label, there were a diverse group of things running around. And I think that was an important insight that tends to get lost sometimes. who lost the ability to connect with other human beings. So their social skills atrophied. This is something contemporary psychiatrists would refer to as the positive and negative symptoms of schizophrenia. But underlying the definition of schizophrenia here is a detachment from reality. So you're hearing voices, you're seeing visions. You're thinking people are plotting against you. directly to you. And because of that, it has these consequences of how you're connected to the rest of the world and what your emotional life is like. Yes, your emotional life flattens out, your language capacity deteriorates, your ability to relate to other people either vanishes or becomes caught up in the web of delusions where you think people around you are plotting against you or doing terrible things to you. And is that a different world than the world of bipolar and the world of depression. Yes. The Greeks recognized, and the Romans, ancient Greece and ancient Rome, recognized different forms of insanity, as they called it. So melancholia would have been the term the Greeks and the Romans would have used. And it survived and was very much around. And I think That... is a form of depression. What's happened now is... major depression has become a catch-all category. So it embraces both what we might think of as milder forms of emotional distress, along with what melancholia referred to, which was really a kind of depression that had psychotic features, this loss of contact, as it were, with everyday reality. So something you would talk about, maybe like a clinical depression. And by the way, we century is like a minefield. Yes, very much so. So here's a very strange bit of historical record. The other distinction, and the distinction we're grappling with, so we have people whose depression is of such a scale, they're threatening to do away with themselves. They've retreated into a complete, almost immobility. They're overwhelmed. [35:00] by senses of sadness and loss, and if they're religious, that they're damned to hell, all those kinds of things. So we have this psychosis. that we've been talking about. We have something also that the ancients recognized, dementia, the loss, really the loss of, of our mind, as it were. Um, But then we also have other kinds of disturbance of our mental faculties that generally we think of as more minor, but I don't want to make light of them because often people that suffer from these things genuinely suffer pretty badly. But those things we in the 20th and 21st centuries tend to talk about as neuroses, neurotic diseases, psychotic diseases. In the 19th century, neurosis was a term that meant things rooted in the brain, as you can see from the root of the word, and psychosis was stuff that came from the mind, the psyche. And yet sometime in the late 19th century, those things crossed over. And so when we talk in the present, we do tend to distinguish between the core, really the most severe forms of mental disorder, which would include things like Alzheimer's disease and other forms of dementia, would include very serious depression, would include bipolar disorder where people oscillate, either have extreme mania, so they're not getting any sleep, they're talking at an extraordinary Their behavior is very hard to tolerate, and they're exhausting themselves, and they may even die from exhaustion if it's not controlled. very often that alternates with periods of depression. So that was a category that was captured initially as manic depressive illness, and later on evolved into bipolar disorder, and then separating out depression and major depression separately. But then there are a whole bunch of other things like, for example, phobias. People can't go outside because they find it too frightening. Milder phobias, I can't go in an airplane because it's going to crash. I can't go to school because it's overwhelming for me. So school phobia emerges as a diagnosis. A disorder that at first attracted Freud, hysteria. And I wish to say you wrote a book. on hysteria. I mean, hysteria, Every classification we're talking about has been used and abused by every layer of society, including institutions, including just culturally. The word hysteria applied to different races disproportionately, to different genders disproportionately. So we're in this crisis of trying to figure out what to do with this super complicated human mind. and in so doing can lead to some abuses. Yes, they do. As you document. If you look back at the asylum era, born in this period of intense optimism, and then the claims to be able to cure these vast numbers of patients were overblown. I do believe the early asylums actually did good work and that some patients, did very well and recovered as a result of their stays. But what happened, they weren't discharging 80% of their patients. They were discharging 35% or 40% of their patients. And what that meant is every year left behind were a batch of chronic patients. And then the next year you repeated it. And over time, what that means is the ratio of new patients to chronic patients gets worse and worse. And more and more, the image of the asylum is defined by the chronic patient who hasn't recovered and maybe spends years or decades there and only leaves in a pine box. So the image of the asylum declined drastically. As they became more and more overcrowded, conditions in them deteriorated. Patients were often abused. Psychiatrists didn't know what to do with them. And they faced a problem in the late 19th century. You'd promised 70 or 80% cures, but we're not seeing that. In fact, when we calculate cures on the numbers of people in the asylum, it's more like 10% or 12%. That's the way you can play with statistics, because that's all the old patients mixed with the new, but still, it looks very bad. How do you explain this, doctor? You promised us one thing, and you delivered something quite different. [40:00] The answer came in a way of blaming the victim, in a way of saying, well, you know, what we didn't understand was that mental illness is a fundamentally biological condition. These people are... evolutionary throwbacks. Evolution was generally thought of as a progressive onwards and upwards, but these people had fallen back into a lesser form of existence. They'd lost their essential humanity because their brains were defective. So what emerged then was the idea of degeneration, the idea that these patients were degenerates. They were people with an inferior biology. because they breed like rabbits. They didn't have any self-control because of their diminished humanity. This is the narrative. This is the narrative. And so... What it did was provide a justification for locking up people in asylums that wasn't therapeutic at all. It was just keeping them out of the way. And then it led to the justification of sterilization. Exactly. Based on the same argument. Maybe we can release them if we make sure they can't breed. This is the beginning of the darkness. It is the beginning of the darkness. My own state was one of the pioneers in this process, and it continued to sterilize mental patients up until about 1960. 1960s, over 60,000 sterilizations have been performed in the U.S., with California performing a disproportionately high number. That's correct. But even more serious consequences could flow from these set of issues. When you start talking, one British psychiatrist said that If his patience, that were coming into the asylum had been puppies. We'd have tied them up in a sack because they were some horrible mongrel, not a purebred dog. Tied them up in a sack with some lead weights and throw them in the pond and drown them. That kind of language is very, very dangerous. them, even though they were enthusiasts, the eugenicists who said, "Best get rid of these people, put them to death," that never really acquired anything. mass support. But what happened in Germany once the Nazis came to power is they seized on these notions and that the idea that the mentally ill were, as they put it, useless eaters, people consuming resources but never going to get better, just a burden on the state. Their lives weren't worth living because after all, they had this serious mental illness. So First you sterilize, and then you go, but we're still supporting all these people. And so Hitler starts something called the T4 program after the street name of the house where this was concocted, Thierensdasser IV. And the mentally ill were the first people to suffer from the final solution. It was in the mass killing of the mentally ill, which may have been as many as a quarter million people, that the technology of the gas chamber was developed and the technology of this of disguising the gas chamber as showers was developed. And so, The patients were... taken away to a number of psychiatric centers and systematically put to death. And they had the crematoriums and the black smoke, and the local people talked about the buses that were bringing them in as killing crates. So they were aware of what was going on. Were they influenced by the narratives that were born in the United States? Yes, absolutely. About that sort of thing, and lacking the checks and balances that, Mm-hmm. It was relatively easy for Hitler to... to do that and particularly with the war looming the idea that we're going to support all these useless people let's Kill them. And German psychiatry, for the most part, collaborated with that process. I wonder how many people throughout that whole journey in the psychiatry profession sort of were brave enough to speak up like, hey, maybe the sack of puppies. kind of language is a problem? That's the really nasty direction that that language could lead to. And it was symptomatic of the kind of stigma that tends to attach itself to mental [45:00] illness and this sense of hopelessness. But if you're a healing profession, If you enter psychiatry thinking, I'm going to do this to help people, to cure people, to make their lives better, to just become a glorified boarding housekeeper, keeping them under lock and key, or in the alternative to collaborate in the sorts of awfulness that the Nazis perpetrated, that's something from which decent human beings tend to recoil and decent psychiatrists tended to recoil. And so, Still thinking. as they did by the end of the 19th century. that mental illness was predominantly a biological Problem. Some of them began to say, well, maybe biology as well as being the problem could provide the solution. Maybe we should look for ways to intervene in the biological systems of these people and make them better. The same logic that applies, I would say, in the present for many working in the field. But in a cruder form. But in a very different form, exactly. If we can just speak about the Nazis a bit more, you highlight that America financially supported the German psychiatric researchers with deep Nazi ties like Ernst Rudin, who was the key architect of Hitler's mass sterilization and extermination laws. the American narratives of the psychiatrist that these are lesser biological beings, and then the financial support and the ties continued. Yeah. So one of the organizations that recognized that mental illness was an acute social problem, very costly to the state, inflicting all kinds of suffering on people was the Rockefeller Foundation. What we don't realize today is that the involvement of the federal government in medical research, and indeed scientific research, is a World War II and post-war development, partly the Cold War and Sputnik and all of that. But that's when big science and big medicine got funded in extravagant Science was an orphan, it didn't get money from the government much, and medicine even more so. So to the extent that Medical training was reformed. That was the the product of investment by the Rockefeller Foundation, enormously wealthier by the standards of the time. Come about 1930, The Rockefeller Foundation decided it... it needed to concentrate its resources and pick priorities for the money it was investing. And it may seem a rather strange thing within the whole range of medical areas that it could choose. It chose psychiatry as the one that was going to invest in. And I think it, did so in part for... precisely because scientific research in psychiatry was so backward. partly because it was such a pressing public problem. And partly, and this was less funny, public, but nonetheless, I think played an important role. Several of the trustees of the Rockefeller Foundation had direct experience of mental illness in their families, wives who'd been institutionalized as schizophrenic. In one case, a wife who murdered the children and killed herself, leaving her husband as a major actor in the Rockefeller Foundation, bereft and, of course, inclined then to support research in this area. Rockefeller... spread its money very widely, precisely because it didn't know where to spend most of its money. So it did some support of psychotherapeutics. It supported a number of the then extant therapeutic. experiments going on. And it supported work in genetics. And one of the geneticists it supported, Ernest Rudin in Germany, who was the leading German researcher in genetics and mental disorder. And Rudin, because he's absorbed the lessons from California about sterilization, became a very enthusiastic proponent of that, and then a supporter of murdering mental patients. That it sometimes can be captured by certain ideologies and in so doing do a lot of damage to humanity. But ultimately the beacon of hope for the future of humanity lays in the scientific method. [50:00] as it is. So everything we're talking about, we get to see How you. F up. in a major, dark, disturbing ways throughout the 20th century in the psychiatric profession. But that should be instructive lessons of how we proceed forward to do better and better and better. We can discuss a series of therapeutic experiments on... people who were shut up in a double sense. They were locked away, and their voices were not heeded because it was the product of their madness. And so what we see in the first five decades, really, of the 20th century is people with a variety of motivations, including the desire to improve a lot of the mental health, engaging in uncontrolled experiments that had terrible results. And the science behind it was shaky, but nonetheless, it existed. It wasn't just plucked out of the sky. And yes, it eventually, those things break down. I mean, the clearest case of that, because it's the most extreme of these, at least in the public imagination, is lobotomy. The idea that you're going to solve psychotic breakdowns in people by excising part of their brain, initially by drilling holes in the skull and injecting alcohol or using what looks like a connections between the brain. And then later, when that process seems to be too slow, the Henry Ford of lobotomy, his daughter said Walter Freeman aspired to be the Henry Ford of lobotomy, the one who could mechanize the production of it and get it done fast. He invented the ice pick lobotomy, where you used an ice pick in the orbit of the eye, banged it through the bone and wiggled it about and severed. I mean, it's just hard to even describe. So this is from the 1930s to the 1970s. Yes. Freeman starts his work in 1936, borrowing from the work of the preceding year of a Portuguese neurologist named Egos Moniz. And Moniz wins the Nobel Prize in medicine in 1949 for lobotomy. So it's important to see that. 14 years of experience, and yet that won a Nobel Prize. I'm sure that's one they'd like to retract. So he popularized Walter Freeman, the ice pick. And his particular specialty after the war became this ice pick lobotomy because there there were over half million patients in America's mental hospitals. Freeman was convinced this operation was a cure-all. And so he traveled around in a which he called the lobotomobile. And he would descend in the summer on state hospitals, and he would teach them how to do this ice pick lobotomy. This is, by the way, image of the tool. Yes, those are the tools he used. Originally, he used an actual ice pick, and then he developed this. This is what he developed? This is a state-of-the-art technology? This is a state-of-the-art with a hammer or a mallet. Oh, no. Yes, I'm sorry. It's very distressing. I don't know. You having to write about this, by the way, is a lot. It's really very, very, very, very difficult. I came across, for example... A picture of a woman naked woman being dragged away by attendants to be lobotomized, and she's resisting with all her might, and to no avail. You have a picture there of Walter Freeman lobotomizing a patient in Washington State. Freeman was ambidextrous, and when he taught neurology, he would draw simultaneously with his left and right hand, and he could do it perfectly. When he was performing got tired, he switched to his left hand, and he sometimes would do twenty or thirty lobotomies in an afternoon. And he boasted, 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. So this was a very ugly episode. How did it die away? It really took time. generational change. Some of these lobotomous continued to operate into the 60s, even to the early 70s. But the younger generation who became acquainted with the really worst failures of that regime, the people on the back wards who were incapable, [55:00] continent who were basically zombies, had lost all mental power, they rebelled against this. And by then they had a different treatment in the form of antipsychotic drugs, which looked much more like what regular medicine was doing, and didn't have these horrible overtones. And of course, In the popular mind, I think... the the, probably the most famous instance of telling the public about some of these interventions was the film of Ken Kesey's novel One Flew Over the Cuckoo's Nest, where you see Jack Nicholson giving, I think, the performance of a lifetime. who is given ECT electroconvulsive therapy in a very dramatic rendition of what that was, not really... what was going on by the 1970s with ECT, but nonetheless, certainly what had been going on back in the past. And then finally, when ECT doesn't, smash him to bits. They lobotomize him and the film ends obviously with him being smothered to death because Chief can't bear to see him in the state that he's in. So that fixed in the public mind. some of the images of these things. It was one of the things that gave electroconvulsive therapy such a bad name. So we'll actually, not to fast forward too quickly, let's talk about the full journey of everything we've been talking about. So we mentioned the asylum era that began in the mid-19th century going to the 20th, and we talked about the narratives. And we talked about shock therapy of 1933 to the 1960s, where you were putting patients in deep hypoglycemic comas using large doses of insulin. Yeah. So as I mentioned, for psychiatrists who went into the field and were ambitious, but who also wanted to think of themselves as therapeutic patients, agents, to just sit there passively and contain the patients was very unattractive. And so they looked around for ways in which perhaps biological interventions could be used to ameliorate this condition that they still soar in largely biological terms. Now, in some ways, one of the crucial early things, ways in which this thinking went and which affected a large number of patients was this. One of the few diagnostic triumphs of psychiatry in the early 19th century as the profession began to emerge was that it began to distinguish a group of patients who were deemed to be suffering from something called general paralysis of the insane. That encapsulates two things about what was going on. First of all, Paralysis. the gradual loss of motor control ability to walk ability to swallow ability to talk So those are primarily what we think of these days as neurological issues. But those were accompanied by bizarre issues. psychiatric symptomatology. These were people who thought they were Napoleon or Jesus Christ, or the richest and sexiest man in the world, or Mary, the mother of God. They were primarily men, but they were also female victims. At the turn of the 20th century, as many as 25% of the people being admitted to asylums were suffering from general paralysis of the insane, or GPI for short. There have been a lot of suspicions about this being connected somehow to sex and to moral dissolution and so forth. But what? evolved in the early 20th century was the discovery of the actual origins of this disorder. So I've said psychiatry has been looking for the underlying pathology that lies behind mental diseases. This was one that at the Rockefeller Institute, they discovered That the organism that causes syphilis was residing in the brains of the people who were suffering from GPI. This was, in fact, tertiary stage of syphilis. Syphilis is still a real public health problem, just like AIDS in the late 19th century. It was everywhere. And, [60:00] You first contract syphilis in the primary phase, You have pain. But then it goes underground. And you think it's gone. And it looks... The way chickenpox virus looks, and can surface years later, right? It lurks, it lurks, and it's insidiously damaging. Sometimes it attacks the heart, and people drop dead of a heart attack in their 40s. Oh, he died of a natural heart attack, but in fact, it was the syphilis. Or it attacks the central nervous system, the final column of the brain, and then you get the paralysis. And then you get also the psychiatric symptomatology. So when that was discovered, That suggested that mental illness might have an infectious origin. tertiary syphilis, GPI, went on to win for somebody who developed a treatment for it, a Nobel Prize, one of only two awarded for psychiatric innovations. One was lobotomy, the other was giving people malaria to cure their syphilis. In case people didn't Hear that. giving people malaria. Yes, in order to cure syphilis. So there was an Austrian doctor, Wagner Jareg, who had long thought that fever could be used to cure mental illness. And he tried rat-back fever. He tried giving people typhoid vaccine that creates a fever to no avail. And towards the end of World War I, the Italians were fighting in World War I on the side of the British and the Americans and the who had malaria. Malaria was endemic in those years in Italy. And they brought him to him and he extracted the malarial blood and injected it into a series of patients with GPI, with general paralysis of the insane, and claimed it cured them. We know from later on when he fessed up that those claims were wildly exaggerated, but they were widely accepted. And malarial treatment spread to Britain, it spread to Germany, it spread to the United States. Sometimes it was vials of malarial blood, but very often mental hospitals had actual colonies of malarial mosquitoes. straight jacket and you're put in a room and you can't move and musculares are buzzing around and they bite you and then you develop malaria and you got a Nobel Prize for this Yes, in 1927, he got a Nobel Prize, because this was a condition that was invariably fatal. And the claim was that somehow the The malarial fever worked. Now, there are two possible ways. Um, von jarig thought it stimulated the immune system to attack whatever it was was causing the insanity but the other possibility was the following. When you, um, have the malarial parasite in a test tube and you heat the test tube to about 105, 106 degrees, it dies. So the idea potentially was you were sort of burning the parasites out of the brain with this agent. And because people were pretty unsophisticated about statistics, and because the idea of a controlled trial had not yet come to pass, this treatment was used extensively for a couple of decades. What caused it to stop, and you talk about the progress of science, was the discovery of penicillin, which was a real magic bullet. So once you had penicillin, you weren't going to continue treating people with malaria, so it died away. But it was the first such treatment. And here's the other way this desperate remedies that develop in this period between the mid-teens and, say, 1950. The discovery of the syphilitic origins is of general paralysis of the insane occurred at a time when medicine had undergone a profound transformation. In the late 19th century, the work of Louis Pasteur, who was a chemist, not an MD, and the work of Robert Koch in Germany, had uncovered the the origins of a variety of Diseases. and suggested that bacteria were the reason why people sickened. And that led, of course, to a public health triumphs, because initially it didn't lead to antibiotics. But for a lot of these diseases, even viral diseases, [65:00] diseases like rabies, you could develop a vaccine. And the vaccines were phenomenally effective. And so, Um, that was one way in which the new germ theory of disease transformed medicine and tied it into the laboratory and into science in a new way. The other was the adaptation of Pasteur's theories by a British surgeon named Lister. who Previously, when pusses develop post-surgery. People thought that was a good sign. Lister said, no, I don't think so. This is actually these nasty germs causing this. And so we're going to do antiseptic surgery. So he sprayed carbolic acid on the wounds to try to kill the microbes. Most of his colleagues thought he was nuts, thought he was just, this is ridiculous, these microorganisms. You couldn't But lists have prevailed. And eventually we move from antiseptic surgery to aseptic surgery, which is what we have now, where you try to have a sterilized disease. set of instruments in a sterilized environment so you don't infect things, right? By the way, these are definitive examples of progress in medicine. Absolutely. Penicillin, making sure there's no germs in your surgery. So these are all just refreshingly clear examples of progress. The reason I say it's refreshingly clear that there's progress, there's not a refreshingly Yes, there haven't been the dramatic breakthroughs that I think everybody in the field would hope for. There's some debate about how powerful what we have done is, and I think it's reasonable to debate that, and to also acknowledge that there is important progress, limited as it is. 25% of the admits to a mental hospital actually suffering from an infectious disease. Medicine in general has now tied its fortunes to the laboratory. The idea that disease is caused by bacteria, we can't yet see viruses. It is a very powerful one. And that notion that disease is caused by bacterial infection acquires great momentum, but it hasn't touched psychiatry. So medicine now has interventions that work. and sometimes quite dramatically, you know, the first patient given diphtheria vaccine, diphtheria causes a leather-like membrane to grow over your throat, and you die choking to death, and if you have a child and you watch that child die like that, you will never be over it. So when you had something that warded that off, That improved medicine's image dramatically and improved its financial prospects dramatically, particularly as medical training became reformed and changed. more involved with science. you So, That hasn't applied to... to psychiatry until syphilis comes along. Now we have the model that an infectious agent can cause people's minds to go, Amok. So, the very person who invents the basic distinction between kinds of psychoses we still use today, schizophrenia, schizophrenia, and bipolar disorder. Emil Kraplin begins to think, you know, there may be something infectious about the mental illnesses we're treating. And one of the people he trains is a young psychiatrist from the United States named Henry Cotton, who's also been trained by Adolf Meyer, who is the leading American psychiatrist of the first 40 years of the 20th century. And when he comes back from Germany, having spent a year there, Meyer secures him a position as head of the New Jersey State Mental Hospital at Trenton. And he's. Cotton is an ambitious, reforming man. He wants to bring psychiatry back to medicine. He also wants to chuck out all the old stuff. He doesn't want chains in his hospital. He doesn't want, if he can help it, straitjackets. So that goes away. But nothing seems to change fundamentally. He still isn't curing patients. And then he comes across this idea of focal sepsis. [70:00] idea that Low-grade infections can lurk in the body, and what they do is release toxins into the bloodstream and the lymph. And hey, imagine if those toxins get to the brain, what's it going to do? It's going to poison the brain and the brain is then going to act up. Mm-hmm. So, We don't have antibiotics, so what are we going to do about this? Well, we can perhaps locate the bacterial infection, and then we can get rid of it. We can engage in what he calls surgical bacteriology. So the first obvious target here is teeth. Your teeth lurk close to your brain. They're often infected. that infection often goes untreated for a time. So we pull a lot of teeth. Patients don't get better. Maybe the theory is wrong. No. Totsils. "They're getting infected, so we'll remove them." Still don't get better. Well, they're swallowing. the bacteria. So we remove stomachs and we move spleens and we remove colons. And we claim to be curing 80% of our patients. And rich patients come from all over America to be treated with this novel treatment. It's crazy. Cotton gives a series of lectures at Princeton, the Vernetzum Lectures, which are given by Nobel Prize winners. There's a very prestigious series. It's published by Oxford University Press and Princeton University Press. The New York Times hails it as a great breakthrough. And in reality, 45% of the people who get the abdominal surgery die within a year. So they're cutting out stomachs. Yeah, they're cutting out stomachs. There's this passage in one of his papers where he says, is on a construction site and can be dispensed with resources. And you think, "Oh my god, If you... were released from Trenton and you had no teeth, People immediately knew you were an ex-patient. Because the word is spread. And this goes on for... Starting in 1916, Cotton drops dead of a heart attack in 1933, but he's succeeded by three people he's trained. They drop the abdominal surgery, they use colonic irrigation, but the teeth and the tonsils keep being pulled. I interviewed the dentist who had come to the hospital in 1916 and must have pulled several hundred thousand teeth. And he retired in 1960, which was when that finally stopped. And he was convinced Cotton should have won the Nobel Prize for this. Well, can you just give some intuition, put ourselves in that mind space? I mean, presumably these are smart human beings. Why were they fraudulent in the reporting of how effective it is? Why are all the people that are participating, both the doctors and the general culture? It's extraordinary. So obviously, many of the interventions I'm talking about are very powerful interventions conducted by people in white coats and stethoscopes and scalpels. Powerful, by the way, by the amount of impact they have on the human body, not powerful in terms of how effective they are. Yes, powerful as well in terms of placebo effect. Look at what I am going to do to you. And yes, it's going to hurt and it's very intimate, but it's going to psychiatry trying to figure out how much of the improvement we're seeing. placebo effect and how much of it is the active effect of whatever we're doing. But by the way, on that small tangent, let's return to that. Perhaps often, I, for one, can tell you that for me, for my mind, the placebo effect, even when you tell me it's placebo, will work. But not only if you have combined an actual gigantic operation that is physically, mentally, in every way life-changing, everybody around you in lab coats, all of society is telling you this is going to be life-changing. I get it. That's like the most pure kind of placebo effect. It's placebo effect that comes believe this is going to make them and from the person conducting. And it's easy to deceive yourself to see what you want to do. to see. So anyway, that was one episode. Um, We talk about triumphs of medicine. So let me talk about one of the real triumphs of medicine. [75:00] 20th century medicine. which is interesting to refer to because... It wasn't a cure. just like psychiatric drugs aren't a cure for mental illness. It was a symptomatic treatment, but it transformed lives. And that was the discovery of insulin. in the 1920s. Previously, particularly what we now call type 1 or juvenile diabetes, was a death sentence. You got it, and whatever you did, you tried various quack remedies, you tried diet, you tried all sorts of things. The inevitable thing was it killed you. And then came insulin. Now, insulin doesn't mean you're cured of your diabetes, but what it means is you can live a relatively normal life and your lifespan is greatly expanded. So by any measure, you have to say that's dramatic progress. But, Insulin is something our bodies produce, we hope, unless we're really seriously diabetic. Those of us with type 2 diabetes, our bodies resist insulin, and we have to resort to other ways of trying to cope. But if you get too much insulin... it makes you unconscious. And I, That's how another one of these desperate remedies came along. A man named Sackle working in a German clinic for drug addicts, they were putting people under mild comas to help them through the withdrawal symptoms as they got over their addiction. So he was familiar with that. And when he moved to Austria, He decided he'd try this as a treatment for schizophrenia. And so he put people into comas, sometimes comas that would last hours, days. They would be revived by giving them glucose, usually intravenously, sometimes not. During the time they were in comas, they often seized comas. had seizures. He saw that as a therapeutic sign. And he claimed that this insulin coma treatment cured 80% of his. 80% tends to come up again and again in these treatments as a sort of percentage that you cure. And he was invited to New York and demonstrated this at the Harlem The visit to America was, I believe, 1936. And Sackle ended up settling here. He had a very lucrative private practice in New York. And when he died, he left his partner, I think, in a state of about $2 million, which in the early 60s was a very substantial amount of money that he'd earned from practice, right? So insulin coma therapy was widely adopted. What kept it, from being a large-scale thing was it required an enormous amount of nursing and medical attention, because people were literally hovering on the brink of life and death. They could go into a permanent coma, they could just die. Vital signs had to be monitored, they had to be brought around very quickly if need be. And there's some evidence that the treatment killed brain cells. And when Sackle was told that, he said, yes, that's probably true. They're killing the schizophrenic brain cells. That's just nonsense. That's just nonsense, but that's rational. Insulin comas weren't subjected to a randomized controlled trial until the 1950s. And when they were subjected to a controlled trial, they failed it. and so It died out. That's, I guess, scientific progress again, in a way, but took a long time. One of the people who received insulin coma therapy, have you seen the film A Beautiful Mind? He did receive insulin coma therapy, ironically, actually, at Trenton State Hospital where Cotton had been. John Nash received. John Nash got insulin comas, and they were going to lobotomize him. And they didn't. But he was at risk of that. We should say that this treatment, patients with thrash mode and convulse before falling into a coma, the treatment required a course of up to 60 comas. It turned out to have a mortality rate of 1 to 5 percent and caused significant brain damage and obesity, yet was hailed as a miracle cure for schizophrenia. Yes, that's right. John Nash, one of the great minds of the 20th century. [80:00] It's one of the treatments he was subjected to and well represented actually in the film of A Beautiful Mind. So I mentioned seizures also in the Austro-Hungary in this period. Another... psychiatrist, decided that you couldn't be both schizophrenic and epileptic, that there was somehow an antagonism between the two. So if you had epilepsy, you didn't have schizophrenia. If you had schizophrenia, you couldn't have epilepsy. I should say at the outset, that's not true. But that's what he believed. So then the logical next step was, well, if we could create an artificial epileptic seizure, maybe we would drive out the schizophrenia. So, What to do? He first tries injecting camphor. natural substance. Natural substances aren't necessarily benign substances. That caused abscesses, and it wasn't very effective. He sought an alternative, and he settled on something that was... called Cardiosoft. or Metrothal, depending which side of the Atlantic you were on. And injecting that into a patient usually caused a seizure, a big seizure like a grand mal seizure where your body arcs back, your legs contract dramatically. You can fracture spines and hips and bones. at such a rate that it fractures. These were among the complications that Metrosol produced. More than that, he himself conceded that between the injection and the seizure, the patient felt as though he were on or she was on the brink of death. Now imagine, Pretend you're a mental patient. You're brought in in a straitjacket. A man in a white coat with a big hypodermic injects something into you. you feel as though you're going to die. And maybe that lingers for two, three, ten minutes, and then you cease. with those possible fractures following violent seizures it's violent and hard to witness and is very unpredictable so it's used but people are not very happy and that's how we get electroconvulsive therapy, electroshock, as it's first called. Two Italian psychiatrists, Saletti and Binni, experiment with electricity, and they first experiment on dogs. And they make a mistake initially. They have an electrode on the head, an electrode on the anus, The electric current passes through the body. It stops the heart. The dogs die. So that seems a dead end. And then somebody says to them, you know, you should go to the Rome slaughterhouse and see the pigs being slaughtered because you learn something very interesting. So they go and the pigs are dangling by their hand legs. And as they come by, two electrodes across their head. Electroshock, They convulse. They're unconscious. Their throats are slit. and pork arrives. And, So, they try that on dogs, and current passing through the brain, it turns out, doesn't kill them. So they decide to try it out. They pick up a transient homeless person at the Roan, Train station and they bring him in and And they... They try it, and at first they don't use enough current, and nothing very much happens. And they're very white-faced. They're quite worried. They're off in the corner. We have descriptions of this, and they're talking. What should we do? Well, we'll up the current. And the patient hears that and says, it's not another one. That's deadly. They do it anyway. And he convulses another grand mal seizure with the same problems of spinal fractures and hip fractures and so on. Not universally, obviously, but often enough. And he stops breathing. You can imagine the scene. And then he spontaneously starts breathing again. And when he comes around, he's in contact with reality. Oh, we've got this miracle cure. And it's very easy to administer. Cheap. Doesn't involve injecting things into people's bodies. And So, that quickly spreads. across the Atlantic and to other parts of Europe. Um, And ECT becomes a very widely used system. intervention. couple of things to [85:00] say about this. Um, It turns out it's not very useful for schizophrenia. Remember the connection between seizures and seizure and schizophrenia that was originally posited. But it seems to work in cases of depression, suicidal depression particularly. Fast forwarding to the modern day, And this is something I... learned by reading a bunch recently. It seems to be one of the few evidence-based scientifically backed method that actually work for clinical depression, for serious depression? Yes. If we fast forward, we're looking at, in some respects, a different animal, for reasons I'll explain. This is unmodified ECT. Yeah. So we're talking about unmodified ECT, which rules the roost, really well into the 1950s in some places, even into the 1960s. And so it is associated with all the problems of fractures that we've talked about. It's also associated with memory problems. People often lose memory. There's some dispute about how serious that is, but it's pretty widely recognized. That's one of the prices you're going to pay for that treatment. Um, The thing is, for mental hospitals in the '40s and '50s, ECT was much more used as a device to control people's behavior than as a therapeutic intervention. It was quite punitive, seen as such. Patients didn't want to repeat, and so they sort of controlled themselves a bit. But yes, we don't know why it, quote, "works." But more recent work, starting in probably the 1990s, and I'm going to get in trouble with some people for saying this, because you mentioned patients and psychiatrists who swear by ECT. There are others who swear at it, partly because of the memory problems I alluded to, and partly because of claims that it may cause problems. Brain damage passing electric currents through the brain. possible. What changed ECT a bit Quite a bit, actually. was giving muscle relaxance. so that people didn't thrash about, and the fractures were largely a thing of the past. When you introduce these muscle relaxers, originally they used curare, but then they used other more modern drugs to paralyze the muscles temporarily. Problem is that would also paralyze your breathing muscles, so that's not too good. So it became a more complicated procedure because you needed an anesthesiologist, breathing support, and so forth during the procedure. But you did eliminate the fractures. It still was a very... widely disdained practice, I think, particularly when they had drugs available, The thinking was that, well, we'd sooner use those, but the drugs turn out to be only partially effective and pretty ineffective very often for suicidal cases and cases of extreme melancholia. Now, A couple of things to say. Very often, ECT has to be repeated at intervals. It's a kind of maintenance therapy. So it hasn't cured things, but it temporarily alleviates the symptoms, and the temporary may be fairly lengthy, but nonetheless, very often things will recur. The memory problems can be quite severe. The worries about brain damage are i think certainly things we have to be very cautious about and when we talk about treatment resistant depression that's an interesting concept to me what it means is those are the patients who don't respond to drugs they may not have a different disease but the drugs don't work for them hence treatment resistant and The numbers of psychiatrists who are willing to give ECT are rather small. And in many states, it's hedged around with lots of legal restrictions. In California, for example, um, ECT now is almost can't be given to involuntarily confined patients, because you have to volunteer for it. So it's unusual. Most medical procedures aren't hedged about by legal constraints like that. And there clearly is a very powerful group of people, some of them psychiatrists, many of them ex-patients, many of them other people who just are suspicious of modern medicine and science. [90:00] who form a group who are very powerfully opposed to ECT. So although it's fair to say there are trials now that seemed to provide decent evidence that for some patients this works and that those patients are deeply distressed before the treatment. It's also still a controversial treatment, I think it's fair to say. Like basically every single... topic, Treatment. problem. subfield of psychiatry today. - Yes, yes. - So everything we say today, there will be at least one person upset and writing a letter. - I think lots of people upset. So if we talk about drugs, There'll be two kinds of people who will be upset. Those who think the drugs are more powerful than they are, or who have been successfully treated by the drugs and go, well, it worked for me, so, you know, stop criticizing it because it really is an effective treatment. And then on the other side of the coin, there are those who... either the drug treatment has been used and it's failed, or they've been left with terrible side effects that don't go away, or they're part of a general group of people that unfortunately is of growing number these days who are so suspicious of medical science and of the drug companies that no amount of evidence will sway them. They are convinced that, you know, they're the drug treatments are poisonous. The Scientologists being a very extreme example of that, who they have a whole museum in Los Angeles, and the title is Psychiatry Industry of Death. And then if you think about all the resistance, for example, that has surfaced to vaccination, in contemporary U.S., and how the trust in vaccination has been destroyed for a substantial number of people, it's very difficult to convince them that they're mistaken. And not just the trust in vaccination. Consequence of that is a general distrust in science. General distrust, exactly. And distrust in medicine and so on. in. After four years of this, first of all, the degree of mistrust will have grown exponentially. And once trust is lost, it's very hard to recover. Secondly, the science itself is being destroyed. Clinical trials that were midway through were aborted. So that knowledge has been lost. You on being trained. because funding has been cut. Scientists with successful careers no longer have the funding necessary to do their work. And it takes at least Six or seven years to train. a scientist at the beginning of their career. And so if you have four years with nobody being trained, you're talking about a decade being lost. And what's lost is invisible, because it's counterfactual. We don't know what that science will lead to or what that medical treatment might medicine and medical research, that not every bright idea we have is going to eventuate in a breakthrough. It would be really simple and wonderful if that opposite were the case. But the reality is we have to go down lots of blind alleys, we have to try lots of different things, and we have to take years to move from the laboratory to practical application. And when we eliminate a whole segment of that. And when on top of that, we diminish people's trust in science. That's a really, I think, a profoundly devastating thing that probably, given my advanced age, I won't live to see the consequences of, but my children and grandchildren will. It really is something cultural that you've got to build up trust in, Mm-hmm. [95:00] and it can be destroyed very easily. So one of the things, go back to the very first question you asked me about, is psychiatry in crisis? Well, genetics was supposed to provide a clear picture of the origins of various mental diseases because they do seem to run in families. So the expectation was, once we decoded the human genome and we could examine bits and pieces of it, that we would very quickly find a Mendelian gene Let us say. hasn't happened. We now use gene-wide association studies, that is throwing everything in the kitchen soup into the picture and then without any preconditions and seeing what relates to what. And if we use 300 small variations in the genome, we can account for about 10% of schizophrenia. That's not very powerful. I'm going to go to the next episode. Beyond that, what psychiatric genetics has... tended to throw up. is something that undermines the distinctions that we've made based on symptomatology. So, if you look, there is a great deal of overlap in the kinds of genetic abnormalities that heighten the susceptibility to bipolar disorder or schizophrenia or autism. There's a lot of overlap there. What that suggests is these aren't distinctive entities in the way that, you know, schizophrenia is, It's my friend Robin Murray, the British psychiatrist, has to say. It really seems to be the extreme end of psychosis, the most serious. But it's sort of on a continuum, you know. And so if psychiatry has to say in 10 years, as some leading psychiatrists are speculating, that. There's no such thing as schizophrenia. There's no such thing as bipolar disorder. That will tend, I suspect, to have pretty bad effects on people's trust in psychiatry. And yet, that's where the science may lead them. we're talking about today, but across a whole spectrum of things, even outside the medical realm altogether. If you lose trust in institutions, trust in science, trust in history, So I think more humility and less arrogance, more willingness to confess the limits of what we can do, more awareness of the dangers of being. Enthusiasm. more skepticism when we're told something is wrong. breakthrough. One of the things I worry about is the tendency of science journalism and medical journalism to hype things up. And then... when the hike turns out to be just that, that undermines trust. You know, so be cautious when things come along. Don't be cautious. so sure that it represents a breakthrough. I'm very worried at the moment. I see ketamine and psychedelics being propounded as a miracle cure for depression. And the evidence for that is enormously weak, is the best way to put it. And I've seen this movie before too many times. You know, I mentioned that 80% cure for Cotton's work, 80% cure for insulin coma therapy, 80% cure for the early asylums. This is overblown rhetoric, and the reality is usually progress comes in small steps. Sometimes it comes in big steps. Penicillin, I think, was a huge step. I was lucky enough to grow up in the era when penicillin and other antibiotics became widely available. They had been overused by then. And so if I had a strep throat, I had something that got rid of it right away. I didn't run the risk of heart valve damage, which in previous times would have been the case. Once in a while, you do have these dramatic shifts, and maybe AI will help us in that regard, but maybe it won't. It's another potential double-edged sword. I should mention that psychedelics, psilocybin in particular, has been demonized for a long time. And so there are studies now out of John Hopkins. They're doing serious studies on cases where it is a [100:00] I think it's nice to give a chance to the different treatments with the rigor of science, but... with caution and basically ignoring, like you're saying, science journalists who are basically hyping every new thing because they have to get clicks and all this kind of stuff. Look at the actual science in the modern day. So in the past, the rigor was not there. In the modern day, there's more. Yes. We can add beyond the realm of science journalists, I think science have this tendency to look for things that make a big splash. Oh, you mean the editors of the major journals? Yes, I think the editors, the major journals, that's what they're looking for. As you know, I mean... Negative findings are very important in science. They're the things that help us avoid mistakes, but they're not the things that are going to get you published in the journal. Right. So it's not just the surface level science journalism. It is also the actual journals and the conferences and the publication process. Having lots of scientists working on these problems in different sites and different places. turns out to be very important, I think, as a check on enthusiasm, as a check on premature claims that turn out to be unfounded. And also because you often partially write, but you're not fully right. And someone else following the same idea is important. it. is perhaps going to be a little closer to the truth than you were. And so it's very helpful to have multi-centered things and not everything under one all-knowing thing. And that's a problem with funding agencies. The maverick scientist has a hard time very often getting a hearing. And we know of lots of examples of that in history where After the fact, we go, oh, well, yes, we should have supported that line of research, but we didn't. Very well put. Let us return to the origins of ACT and how it was applied. But first, if it's okay, a quick bathroom break. Quick 10-second thank you to our sponsors. Check them out in the description. It really is the best way to support this podcast. Go to lexfriedman.com slash sponsors. And now, dear friends, back to my conversation with Andrew Skull. Now we're back just to talk a little bit more about ECT and one flew over the cuckoo's nest. So what can we say about that, that little cultural moment, one of the most famous moments about psychiatry. First of all, Ken Kesey wrote this book about his own experience in a mental institution. Yeah, Menlo Park, yes. How representative is it of the system at the time? Mental hospitals have... had a very patchy and complicated history. He was working actually in a hospital for veterans. Those were largely created after the Second World War, when there were very many more psychiatric casualties among American troops than even the First World War. The interesting thing is we all, by osmosis, know that in the First World War, there was something called shell shock troops and that the military initially resisted recognizing and ultimately were forced to grasp. But in World War II, American psychiatric casualties among the troops were two to three times as high as in World War I. And that's an important part of the history of psychiatry. But the upshot of that was that Post-war, the VA was heavily involved in, first of all, paying to train psychiatrists and even psychologists, and then had in its mental hospital system a considerable involvement with psychiatric patients. disorders. Kesey, well, The book is different than the film. is the first thing to say. Obviously, the film is heavily indebted to the book, but it changes various things. If I may, just going to perplexity, the book and the 1975 film tell the same basic story of McMurphy challenging an oppressive psychiatric ward, but they differ sharply in point of view, tone, and what the story is about. The novel is weirder, more political, and more the film is more naturalistic, character-driven, and turns McMurphy into the central hero. [105:00] Yes, and you have a nurse figure in Nurse Ratched, Louise Fletcher, I think is an equally powerful performance. It's just one of the greatest films of all time, who happens to be, which is unfortunate for, you know, psychiatry. Yes. It's very interesting. I used to teach a class called Madness in the movies. And I didn't just use, in fact, I used relatively few contemporary films. And among all the films from... back then the one Almost everybody in the class that's seen was one flew over the cooker's nest. So, eight 19 and 20 year olds uh in 2015 if i showed them alfred hitchcock's bellbound no chance they'd ever seen that maybe one uh because there were a class of people interested in film but everybody had seen one flew over the cooker's nest on that tangent really quick what is the greatest film a madness in your view. Oh, well. Would that be the One Flew Over the Cuckoo's Nest? I think One Flew Over the Cuckoo's Nest, I think. Oddly, a very different film that appeared at about the same time was I Never Promised You a Rose Garden, which is a much more sympathetic portrait of a different kind of psychiatry, a very Freudian psychiatry. It's really about Frieda Fromm Reichman, who worked at Chestnut Lodge in Maryland and treated schizophrenia with psychotherapy rather than with drugs or other forms of physical intervention. And that was a best-selling novel delusions and a very complicated family background um And again, the film... changed. a lot of things in the novel. That's what films do. My book Madhouse at one point interested Hollywood. And one of the two principals said to me, I really like this story. It's got a great first act and a great second act, but where's the third act? Meaning, where's the happy ending? And I had to say, there wasn't any happy ending to that story. It was just rather grim. Madhouse, a tragic tale of megalomania and modern medicine is the book you're referring to. reminds me of Flowers of Argonne. That doesn't have a happy ending, and that's not about mental health necessarily, but it's about the journey of the institution in relation to the health of a patient. Yes. Pat Barker's trilogy of novels about World War I was turned into a film. I That was quite powerful. It was about World War I and the treatment of shell shock. And I thought it was quite well done. And my friend Patrick McGrath, who's a novelist, wrote a book called Asylum. Patrick grew up in the grounds of Broadmoor. Broadmoor is England's premier hospital for the criminally insane. And he was babysat by some of the patients. And when that upbringing affected his rather macabre imagination. But anyway, so One Flew Over the Cuckoo's Nest, the poverty of the environment, the room that the patients were in, I think fairly successfully recreates that. The way in which staff very often put patients down, didn't listen to them or poke fun at them or even were physically abusive, although you don't see that. Those were all features of mental hospitals. The general boredom of life. sort of there but Yeah, it's hard to represent. You don't... Putting... boredom on the screen will turn an audience off rather fast. What about nurse and this kind of abusive element, you know? Yeah, I think that there was an abusive element in a lot of mental hospitals and it, it was almost inevitable. if you look at who had the most contact with the patients, it was the lowest paid, least respected ward attendants, very few even RNs. And, you know, the ratio of doctored a patient in the large state mental hospitals meant that Patients hardly ever saw a physician, you know. What's remarkable about the film, there are many remarkable things about the film, as well as its [110:00] polemical edge, I think is that the chief psychiatrist that you see in the film is the real head of Oregon State Mental Hospital. He really was. That was his... introduction to acting and i thought he was pretty remarkable actually but obviously there's a lot of exaggeration there but ect was used in the 50s and 60s as a tool of discipline in the hospitals it was also used therapeutically but overwhelmingly it was used as a Tool of discipline and control and that's true to life Lobotomy One of the interesting things we haven't talked about with all these treatments we've been discussing is that almost invariably, Except for the case of the syphilitic patients, for obvious reasons, men were more troubled by that condition than women. It was women that got the brunt of these experiments. So Henry Carton, about 70% of his patients who were treated were female. Lobotomy patients, it's hard to get overall numbers. But those of us who've looked at the records of a number of different hospitals, again and again discover again, 60 or 70% of the patients are female. ECT tends to be heavily female. That's complicated by the fact that it's used primarily, as we were discussing, in serious cases of depression and so-called treatment-resistant depression. And depression is a diagnosis that is more to be found among women than men. Not that there aren't very many men with depression, but again, the ratio is such. Men tend to get different diagnoses. Personality disorders, for example, are very common and more male. Um, ADHD. is more male than female and so on. So, it's good to point that out. I think it It helped end interest in ECT, except for a small handful of enthusiasts, for decades, that film. and probably even now it creates hesitation in people about the treatment um so it It's one that has had a very... powerful and long-lasting effect, I think. I think the surprising thing is I recently learned a friend of mine, tried everything. about 20 years ago, tried everything with depression, and the ECT is the last thing he tried, and it changed his life for the better. That's not an uncommon story. And then I looked online, and there's a lot of stories like this, and before learning of that, my I'm embarrassed to say knowledge of ECT was just one flu over the cuckoo's nest. You know, it has a terrible history in the 40s, 50s, and 60s. There are lots of... The CIA funded Ewan Cameron up in Canada, and... He was giving multiple ECTs a day and reducing people to, well, they couldn't walk, they couldn't talk, they couldn't feed themselves, they were incontinent. And then he built them back up, or so he claimed, but in many cases, they were left permanently damaged. So I could recite lots of real horror stories about ECT, but it's also interesting. If you're honest about the thing, what you just described, that is patients who were on the brink of suicide, who had long-running depressions, some of them. had ECT. and they describe it as life-saving. And, as I say, when more controlled trials have been done recently, there's enough evidence now that it's hard to say this never works. This is just one of these desperate remedies we should consign to the Dark Ages. The complicating thing is... we'd have no clue why it works. It's a purely empirical treatment. And that, itself, I think, tends to put people off. If you have a curable form of cancer, And the surgeon says, well, I'm going to remove it. And she does. That's that. But. Because we understand that. even a little bit even if our knowledge of human biology is pretty primitive we do understand a little bit that cancer is sells dividing uncontrollably and taking up and doing damage to the body and eventually killing you [115:00] And the fact that we can surgically remove it is a big deal. There are lots of disorders. I have high blood pressure. If untreated, my blood pressure is like a 20-year-old's thanks to treatment. It's an ongoing thing. I take the damn pill every day, and it has a few minor side effects, but for me, very minor ones. And it turns what could have killed me via a stroke or a heart attack into a condition that's very well controlled. So, you know, all of these things, they're complicated. It's easy with some of these things with lobotomy. with insulin comas, deep sleep treatments, Henry Cotton's endeavors. those you can just say, well, we'll throw them away. And for a long time, I think ECT would have formed part of that cast of characters. So when I first... conceived the idea of writing Desperate Remedies, the book. It was back in 1981, and I was in London, on a Guggenheim Fellowship at the Wellcome Institute. I hadn't done research in detail, but I was aware there were all these things lurking about that had happened in the 1920s and 30s, and I thought that would be a very interesting thing to study. Luckily, I didn't do it right away, or I did it piecemeal over the years. And I ended up writing a much more comprehensive look at psychiatry really from its origins to now. And I couldn't have written that book back then, and I would have missed all the developments from 1980 onwards, which are very, very important to the overall picture. So 40 years later, 2022. Yes, yes, exactly. Desperate Remedy, Psychiatry, Stroubling Quest to Cure a Mental Illness. I've written a lot of books, and along the way… Part of the way I think I've... being productive and kept interested. I always had at least two projects on the go at once. You can't simultaneously write two things, but I'd have one and I'd work on it. And if I got tired of it, I'd pick up the other one for a bit and then go back. And it also meant when I was working on one main project, I had other things percolating in my head. And I'd I would come across things that were relevant to them, and I'd make a note, and then I'd go back. So when I finally did... Desperate Remedies, I've been thinking about those issues for 40 years. And that made a big difference, I think, to the way I approached things and to what I thought. Because you just... Either like Thomas says, you say the same thing over and over and over again for 40 years, or you learn new things and you broaden what you know and you think about things in a different way because you realize you haven't grasped the full complexity of what you're looking at. What I found with... psychiatry is, there are really a couple of fundamental things that have kept me engaged with the field. One. It's an arena where there's tremendous human suffering and it spreads out and it's As far as I know, and I wrote a big book called Madness in Civilization about from the ancient Greeks and ancient China to now, in every society I've studied, they have to cope with this. It takes different forms. It's regarded in different ways. It's treated differently. But that there are people that deviate so far from the norm of what we regard as culturally appropriate, they exist everywhere. the difficulty of studying it, and then the fact that it is such a complex and difficult subject to understand. The very fact that, we have such limits to our knowledge. means there's space there to examine things in what needs to be a very complicated way. And so it's a intellectual puzzles attracted some very, very smart people, but there's a long way to go. Yeah, we have glimmers of insights about how the mind works, but if you look at the span of human history, we're probably in the very early days of understanding this particular one. I have to, if it's okay, so that we've been carrying multiple threads together. One of the threads that I think - Yes. [120:00] psychotherapy side. We have mentioned the psychopharmacology that will also, it would be nice to discuss when the two clash and there's a revolution where psychopharmacology kind of wins over psychoanalysis for a time. But let us start at the somewhat beginning, the 19th century, Science and then psychoanalysis context. Yes. So, I'd mentioned late 19th century psychiatry, confined as it was to the mental hospital and to people incarcerated in those places, had become very biological. didn't involve time in a mental hospital, but nonetheless, it involved a good deal of distress, as they continue to do. And one of the things that was interesting about 19th century America is it spawned a number of new religions, sort of variants of Christianity. So you had a Seventh-day Adventists. group that still exists, who actually spawned a sanitarium for their depressed congregants that was later taken over by two prominent members of the Adventist church, the Kellogg family. Everybody knows them through cereal, but they ran a huge sanitarium to which Abraham Lincoln's and politicians. It was kind of a farm to go and recover your mental stability and health, and it was all bound up also with beliefs about diet and defecation and all sorts of things. So there were the Mormons or Church of Jesus Christ of the Latter-day Saints. Many Christians don't believe they're really Christian, but they think they are and call themselves such. And one of them was Christian science, which was the invention of a woman named Mary Baker Eddy. And it wasn't just about mental troubles. Mary Baker Eddy developed the idea, and there are still Christian science churches and Christian science reading rooms all across America, that there wasn't such a thing as disease, that it could be prayed away, that it was just a lack of sufficient faith. Thank you. It tended to work, I think, better if it worked at all for psychiatric problems than it did if you had, say, cancer. But Christian Science achieved a considerable number of followers, disproportionately women, but not only women. It began to treat many of the people suffering from what we would think of as the milder mental disorders. And it attracted Both. adherents and severe critics. Mark Twain, for example, was thoroughly dismissive of Mary Baker Eddy. But it was very successful for a time. There were other religiously-based attempts to join in, the most important of which in New England was something called the Emmanuel Movement, centered around the Church of the Emmanuel in Boston, which was an attempt actually initially to bring medical and religious approaches to helping the mentally troubled. But rather quickly, the doctors involved decided this was veering too much in the direction of medically-based therapeutics, and they kind of withdrew from from that enterprise. And it dispensed, I mean, there were, there were talk therapies, obviously with a strong religious component around them. And this was also at a time when, Some... I guess we can call them psychiatrists. They were often neurologists. we're beginning to get lots of patients with these kinds of difficult to treat disorders. Neurology had emerged in America after the Civil War. [125:00] Civil War, provided a lot of naturalistic experiments on what happens to the human brain and the human nervous system when trauma happens. I don't mean psychological trauma. I mean bullets blowing holes in your brain. And so a group of new specialists emerged after the Civil War who claims expertise in the brain and the nervous system. Well, one of the other side parts of that is insanity because insanity is also seen as a. a brain disease. So there is a conflict that erupts in the 1870s and 80s between neurologists and psychiatrists. But the neurologists can't, for the most part, get into the asylum where the most seriously ill patients are. And so gradually, what comes to their waiting room, along with people suffering from things like multiple sclerosis, are people with functional mental And so there's the beginning of an outpatient practice, which is, initially involves some drugs, the use of electricity, not ECT, but the use, for example, of static electricity, because it produces obvious physiological responses, and electricity is seen as dominating the workings of the body, and sometimes tonics of one sort and another, and most notoriously of all, something called the rest cure, which Silas Weir Mitchell, one of the leading lights of American neurology, develops, which is complete bed rest, lots of calories, lots of food, complete lack of intellectual stimulation. Supposedly, this is going to cure you, mainly aimed at women. That's another Evans-backed technique that works well. I've partaken in this, and I know it has helped me. Laying in bed, doing nothing, eating snacks. Virginia Woolf was one of the people subjected to this, and she claimed it practically drove her mad and made her worse. Just to clarify, we're talking about laying in bed, eating snacks. Eating lots of snacks, a very high calorie. bestsellers, self-help books, I suppose you'd call them in the modern genre. One was called Wear and Tear. So the pace of modern life, the telegraph, the railway was all too much, and your nervous system was overstressed. Either your batteries ran down, that was one analogy, or you overtaxed your system and went bankrupt. So wear and tear, that was the problem. Blood. That was the title of the other book. So you got scrawny and all nervous and twitchy. And what you really needed was to build back up your strength, including your nervous strength. Isn't it fascinating to look at that 120 years plus ago? They're talking about how anxiety inducing society is, how much is going on. And we in the modern day talk in the exact same way about social media, the internet, all that kind of stuff. century and think of it in idyllic terms of as much slower pace of life and people, they thought it was stressful in exactly the ways we do. So there was a class of potential patients. Some of them were seeking help in the neurologists and a few psychiatrists who moved out of the asylum. But 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, it still exists, but it was set up to copy the German Research University. 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. I like how you're telling this in a cinematic way, the story of Sigmund Freud and Carl Jung coming to America to give a lecture. I like how the movie - Yeah. [130:00] - You don't know who he is. He's fairly obscure. - We should say the reason you're actually telling it that way is America has... a really defining place for psychiatry. Yes. And then Freud had his own views on America and so on. But this was, in terms of the history of psychiatric medicine, America is central. Right. Many of the in-house histories of psychiatry portray this as Freud's conference in, Mm-hmm. 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 30 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 on the same boat as him and they avoided one another like the plague. But anyway, it's important to see that. And Freud, It's a mark of how important German science and German medical science was in the late 19th, early 20th century, where it was the most advanced in the world, that Freud delivered his lectures in German. And the audience, that wasn't a problem for the audience because they'd all learn German so they could read German literature on medicine. So quite an extraordinary thing. 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. But he's not impressed by Freud. A handful of people are, some of the neurologists. And Freud's lectures explicitly attack Freud's. religiously-based psychotherapy. He says psychotherapy is like a surgical operation on the mind, and only us doctors, or only us thoroughly trained people, because actually he doesn't believe that psychoanalysis is only something that can be practiced by the medically qualified. But the lecture is on psychoanalysis. Yes, it's five lectures. They're published Putnam is a Boston Brahmin, one of the upper-class Brostonians who's extremely well-connected and is professor of neurology at Harvard, and he becomes a Freudian at that conference. So 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. Maybe just to mention a few things, Sigmund Freud, of course, is widely acknowledged to be the father of psychoanalysis. that is the source of many of our behaviors. And then psychoanalysis is a way to delve deep into that mind. And the tools you use to do that is talking. Yes. Freud was trained as a neurologist himself and studied under the most famous late 19th century neurologist Chocot in Paris and translated Chocot into German and endeared himself to Chocot by doing that. That's a clever way to help your career along. But 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. He was accompanied by two of his close disciples to the Clark Conference. One of them, Carl 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. and clever. It is put it was a great hater. If you fell out with Freud, it was bad news. Oh, yeah, yeah. You were excommunicated. If it was Adler, but Jung especially. Jung was, was Swiss and he'd, [135:00] worked in the major mental hospital in Zurich. And he was attracted to psychoanalysis and to Freud. And for the first few years, there was this obvious close alliance. Anyway, so Jung was the person who actually persuaded Freud to go to America. Freud initially, Freud had very low opinion of America. He said it should be renamed Dolaria because it was only interest in the dollar. and it poisoned him and on and on. So as you said, Freud was a master hater. Yeah, he was. And one of the things he hated was America, even though America brought him some fairly rich patients. But the richest patients of all went to Jung. not to Freud. And I think that probably exacerbated this split. Let's actually focus first before the conference on the actual ideas of psychoanalysis. So, Freud was the originator of psychoanalysis in the 19th century. So, tell me about the original case of Anna O. And what is psychoanalysis? Yeah. So, 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 possibly. 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 career, and that involved, he had a close friend named Joseph 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 people, a woman who's now known as the sort of foundation patient for the overpatient for psychoanalysis, who was known to us as Anna O. We actually know she was Berta 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 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. Thank you. dealt with that by developing a notion that what she was suffering from was repressed memories and trauma. This would become central to psychoanalysis, the idea of half-murdered 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. Frey and Breuer collaborate on a book called Studies in Hysteria. There are a series of case vignettes in there of patients Freud is treated. He develops the notion that people have these past experiences. Initially, For example, they have 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. 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. But as you 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. But crucially, you know, the stuff that happens in childhood is important. Yes. The early experiences have a dramatic effect. And I think even some [140:00] biological psychiatrist would agree with that notion these days that, you know, to the extent we've abolish this distinction between mind and body and, and, acknowledge that they are closely tied together. traumatic experiences in childhood, various socialization experiences, loss, and so on, deeply mark the human psyche, I think, and can have... long-term effects that are very powerful. Of course, Freud added a bunch of stuff in the realm of psychosexual stages of childhood. Yes. As he 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 repression of sexuality and the modification of sexuality All of that enters the picture. It's one of the things that ends up dividing Freud and Jung somewhat, because Jung downplays that sexual side of things after the break. So 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 going to tie psychology back into neurology. But he abandons that. And once he's abandoned that, he goes on to develop increased and increasingly elaborate. 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, and so that book, Mark's 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 beliefs. talk therapy. Of course, underlying it, he is building a model of how this whole mind thing works. There's three interacting parts of the personality. First, the id, which is the primitive, entirely unconscious driven by pleasure principle, seeking immediate gratification of basic drives, such as sex and aggression. There's the ego, which is the rational mediator operating on the the superego, which is the internalized moral standards and ideals producing guilt or pride and striving for perfection. So that's the structure. Yeah, 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 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 or something like that. Yeah, sure. Yes, you get that. And 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 Carnegie's and the Vanderbilts of that world. This guy is a U.S. senator who ends up committing suicide in 1925 after a lot of treatment from Young when he fails to win re-election to the U.S. Senate. He kills himself in Washington in the interregnum. But he also gets another one of that brood. Edith Rockefeller marries a McCormick. And she has a lot of psychological issues, and she tries to get young to move to Chicago, promising him she'll set him up in a mansion with lots of her friends, 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 be treated. She's agoraphobic. And so she has a hard time being out, out of her little cocoon. So she's, [145:00] treated there as an example of how peculiar she was, I mentioned the agoraphobia. So she occupies a huge array of suites with all her servants and so on in Zurich. And she takes a train journey, 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 because she can't bear it anymore. And she becomes a Jungian analyst, which is the important thing. And then Jung attracts... Paul Mellon and his wife Mary. Jung's works are published by Princeton University Press with a subvention from that Mellon Foundation. It's a long-running thing. Freud doesn't get patients quite that rich. He gets some rich Americans. We should say that Freud, for his ideas, became quite popular among the intellectual and artist class in the 1920s in America. Thank you. the breakdown of many soldiers from something that came to be labeled as shell shock. The label shell shock intimates, it's 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 blindism, 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 a 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, you're absolutely right, um, 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 the clinical setting, Freud's ideas were not popular. No. The only... Partial exception to that was the mental hospital in Washington, D.C., the only federal mental hospital, St. Elizabeth's. 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, is obviously out of reach. Plus they are much more severely disturbed. So, um, It does happen. novelists, painters, artists, playwrights, and the audience for those elite artists. forms of culture do tend to embrace Freudian's ideas. sex sells in the theater and on the movies, obviously. 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. 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. Well, psychoanalysis is telling stories. It's getting people to recover stories, recover memories, to rebuild. Its elements of psychological conflict and hidden motives and so forth are 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. But it's important to know, circa 1930, there are probably 300 psychoanalysts in North America. If they each, if classical psychoanalysis involving five hours a week, um, It's... they can't treat that many patients, a few thousand. [150:00] when there are hundreds of thousands in the hospitals, right? So what changes that? The war, Second World War. 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 is one of Freud's great supporters, bribes the Nazis to get him out. He travels by train to London, very sick with cancer of the jaw, as he has been since the mid-20s. He sets up shop in 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 the... 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 it either resists being incorporated or the university resists incorporating it. So I think that's a structural weakness for that. transforms things is World War II. To backtrack, what's officially the process for psychoanalysis as Freud and Carl Jung saw it? He said five hours a week. So it's this long, deep dive. Five 50-minute hours, famously. They last 50 minutes because then there's 10 minutes for four analysts to recover before the next patient arrives. And literally, I mean, you think it's not important, but I guess they were pretty strict about this. You're lying on the couch. Yes, you are free associating on the couch. and gradually being coaxed to see as the material emerges what you're hiding from yourself. I mean, initially they tried, this is in the early, early days, they tried hypnosis. Yes. But this is where Freud took the big leap and expanded to free association. Right. So I mentioned Freud training under Charcot. Charcot hypnotized his hysterical patients. We now know a lot of that was fakery. I don't think he was conscious of the fakery, but the patients were on display over and over again, and they worked their routines up very well. deceived him and they deceived the audience. 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 history and didn't want anything to do with the revisions of Freud's work on history. After that happened, Freud, who was a began to develop this alternative of free association and getting people to speak whatever came into their head without a sensor. That was the important thing, that the half-murdered memories were being hidden from you, and the constellation of psychological forces in your unconscious was squashing them down, but they were re-emerging as other kinds of symptoms. We understand. We've talked about all these approaches that didn't work. How well did it work at that time? 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 I hoped would be new tools in it, the then- Heads of the funding program, Alan Gregg and Robert Morrison, especially Morrison, 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. ways of being in the world and we don't have easy ways to measure that to contrast that with the 80 percent promises yes over and over and over and over and it's a long and complicated that [155:00] was very important because Thank you. Another kind of... psychotherapeutics is emerging. 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. So, To focus on the war for a minute, 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 until Pearl Harbor, but the European war had been going on. And they said, look, if we have to fight, we're going to have the same problem we had in the First World War. We're going to train these soldiers. We're going to equip them. We're going to put them in the battlefield, And the psychologically vulnerable among them are going to break down. Mm-hmm. 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 One and three quarter 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, 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 us, I can't speak from experience, but from talking to people who've gone through all this, many of them find the experiences and the memories they 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. bang you're dead we're not dealing with you but um obviously the allies that was not the response um and they quickly had to try to treat these troops to Maybe get them back into the fighting... Lines, maybe get them into support positions, something to cope with the problem, which was Both are It 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. He 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 U.S. military. So you had to train people in a hurry. And even still, it was hard to get enough people trained. And it turned out that the head of the US military, not the first, the first one died. The second one was a man named William Menninger from the Menninger Clinic in Kansas. where he and his brother... ran a psychoanalytic treatment facility. So Bill Menninger became the head of army psychiatry. He concluded that the best treatment for these soldiers breaking down was psychotherapeutic in nature. The origin of their condition was trauma. And so in a watered down way, Freud's ideas, those were the ones that the people that recruited quickly and retrained as psychiatrists absorbed. So they formed after the war. fairly coherent group of people separate from the psychiatrists in the state hospitals who were still very biologically oriented. Another group emerged during the war precisely because you couldn't produce enough psychotherapists who were mds quickly enough psychologists were drafted in and asked to treat. So, What the psychologists discovered was, hey, we could do this stuff too, and we really like it. It's interesting. It's challenging. We should do that. So after the war, similar kind of [160:00] problem. Mental illness is a massive problem. The returning soldiers is a big problem, but it's also a problem in the community. These guys don't, the psychiatrists don't go and work in the mental hospital. They start outpatient. treatment. And by 1958, about 80% of psychiatrists are working in outpatient rather than in the hospitals, right? So the psychologists organize themselves and federal money, again, we need you, we need you, we need more of you. So the VA, the Veterans Administration, and then once the National Institute of Mental Health is established, they start providing a lot of money for training. And they train not just psychiatrists, they train psychologists. So the question is, how are the psychologists going to set up clinical training. So what the psychologists come up with, the clinically oriented ones, is a training program where would-be clinical psychologists spend two years learning basic scientific psychology. and research methods. And then they have two or three years of clinical research. work and experience. And that's very clever because, um, It means... when they start looking for grants, they know how to do that. And the psychoanalysts don't have a clue how to apply for federal grant money. And they don't get any almost... Beyond that, these people begin to work on treating symptoms. The psychoanalysts think to treat a symptom is to play whack-a-mole. If you don't deal with the underlying problems of the personality, They're, interaction between your id ego and superego. You suppress that symptom and another one will pop up over here. Thank you. The clinical psychologists go, we're going to treat the symptoms of what are troubling people. We're going to treat the symptoms and we're going to develop techniques that allow people to cope with those symptoms and eliminate them. And how are we going to do that? We're going to do it primarily through what initially is cognitive behavioral therapy, and later interpersonal therapy, and some other variants emerge. But basically what... they try to do with those techniques is to develop things that work relatively quickly, work specifically on one set of problems or a small subset of problems and try to get those under control. And how does How does it work? You've developed really bad habits. the way you react to being socially snubbed or being ignored, or the way you deal with your co-workers, trouble you're having with your disruptive child, We'll help you see the patterns that you've fallen into, and we'll give you exercises that will work to give you a better way of coping with those things that don't produce these symptoms. I'm oversimplifying, obviously, but basically that's the fundamental thrust of this. Exactly. So these therapies could be packaged, they could be reproduced, they could be tested to see whether they worked. So they had an evidentiary foundation. The psychoanalysts would say, "It's going to take us years and it's hard to measure." These guys were, "Well, we'll measure what happens when we treat people this way." Psychologists. Yeah. The symptoms are what matter, not the underlying more complex thing that psychoanalysts claim to be treating. And so, It's. Shorter. It's reproducible. Whereas psychoanalytic, every patient is a new patient with a new set of complicated problems. things going on. Here we are, we're going to do this. The key figures here is Albert Bandura, Albert Ellis, Aaron Beck. Yes, Bandura and some other psychologists launching this movement. Then later on, Aaron Beck who went by Tim Beck Who just recently died at I think he was 99? I think he crossed the hundred maybe [165:00] Maybe 100, yeah, maybe 100. There's videos of him talking at that age, and he's still killing it so wise. Aaron Beck is a remarkable figure because he was also one of the first in the 1960s to look at psychiatric diagnosis and show how unreliable it was, how difficult it was to get psychiatrists to agree on what was wrong. So he was a psychoanalyst, right? became disillusioned with it. And so there were two strands, two important strands that stemmed from his work. First, he was one of the ones within the community itself who said to his fellow psychiatrists, you know, we're not very good at this diagnosis business and maybe we need to work on that. And that was very important for the movement towards DSM-3. The other side of the coin was He broke with the idea that treating symptoms was a waste of time and joined with the psychologists who already embarked on that journey to say, how can we develop techniques to overcome these problems? self-destructive ways in which people are responding. How can we help with their ability to interact, so interpersonal therapy is much more concerned, with the way in which if your relations with other people break down, that damages your emotional stability. If you repair those relationships, that helps your emotional stability come back. unusual. Most of the rest of the world has what we call socialized medicine. America doesn't have that, so we're used to paying for medical care. And so... Americans were more willing, I think, to pay for clinical psychologists. And they attacked some of the problems of everyday living the more I was going to say minor, but these are often quite distressing things. But those were the things they were most successful at doing. If I look at the literature on CBT, for example, and its uses in cases of schizophrenia, the evidence is pretty poor that it works. And even the evidence for the milder conditions is a bit more ambiguous than they like to pretend. The Cochrane reviews, which are a systematic attempt to assess how strong the evidence for particular approaches to disease of all sorts are, say that at best the evidence for CBT is of low and medium confidence. Indeed, for the milder forms of depression, I think CBT works better than the drugs without some of the side effects that the drugs have. And indeed, NICE, which is the British organization that passes on what treatments the National Health Service will support and which ones are sufficiently evidence-based, has come to that same conclusion. about cognitive behavioral therapy. I mean, it has some elements of kind of surface-level intuitive consciousness Kind of things like. Being aware of and. Adjusting your thought patterns. Being aware of triggers. That get you down and they get a spiral. And then basic behavior changes. Habit changes that lead to a healthier life. So I think. I think this kind of, you know, getting your life together kind of process. Right. It's intuitive that that would have a positive effect on some percent of the population. But as you get more serious and serious into the land of mental disorders, it starts to be a little bit less conclusive. Yes, I think that's an accurate statement of what the way I read the literature. And it's Not a cure-all, but for some patients, this really does seem to improve things. quite a lot. It does make sense that you have developed poor ways of responding to signals from the outside world. they've become habitual and the habits, as we know, are very hard to break. There's a lot of homework, there's a lot of exercises you have to do to try to reconfigure [170:00] the ways you deal with the world. And it's not for everybody, and it doesn't work for everybody, but there's some subset of people for whom this seems to have been Positive effects. So this is the lay of the land. We talked about some of the darkness. Yes. Lobotomies and so on. There is some talk therapy ideas of psychoanalysis. And then there is from the clinical psychology side, cognitive behavioral therapy. Then starts to emerge the psychopharmacology that challenges this whole shebang of talk therapy, period. And can you accidental origins of psychopharmacology that challenges this whole thing. Hardly anybody had conceived of the idea that drugs could be used to treat mental illness. Drugs had been used in the mental hospitals back in the 19th and 20th centuries, but they were usually things that were used to control patients to calm them down. Opiates, for example, they're extremely agitated and so forth. Sometimes marijuana was experimented with, as was alcohol in the 19th century, interestingly enough, given the revival of psychedelics. But... The idea that A drug might be used to actually attack the underlying disease. problem. It emerged... by accident in the following kind of way the drug industry in general had emerged... mostly in Germany, where I'd mentioned the most advanced medicine was being practiced in the late 19th century, from the chemical industry, from, for example, refining coal tar into different substances. That's where we got aspirin. That's where we got a whole bunch of drugs. And gradually, the drug companies become more organized. They differentiate themselves from I think greatly accelerates again World War two greatly accelerates things not least because we discover a real magic bullet called penicillin and then the other antibiotics that we've subsequently come across. Penicillin had been observed by Alexander Fleming famously in his lab in some Petri tube, Petri dishes where bacteria had been killed. Later was one of the co-winners and O'Prize and made a lot of capital out of that discovery. It was really Harold Florey and his team at Oxford who developed the therapeutic potential of penicillin, And actually, Flory flew some of it in his jacket across the Atlantic to America. And it was Americans that solved the critical thing. It took Flory and his team weeks to develop enough penicillin to treat a single mouse. What America learned how to do was mass produce penicillin. And that was critical because it was vital to the war effort, obviously. important. breakthrough. So, um, Drugs, drug companies, grew fatter on that. They embarked on research to try to find new substances they could use to treat things. and a French company named Rompolenk. Thank you. came. across a chemical that had actually been synthesized back in the 1880s in Germany. It was an antihistamine, chlorpromosine. They didn't know what to do with it, but other kinds of antihistamines in the war had been used effectively. They thought, "Well, let's look and see if we can find a market for this drug." The interesting thing to remember in those days is that investigating no controls. You could do whatever you wanted. And you handed stuff out and said, why don't you try this and see if it works, right? So Rome Palenck did that. They thought this might work as an antiemetic. If you have a child who's prone to car sickness, you give them an antiemetic drug. So that was one possibility. Another possibility, it might work for eczema so that people didn't Maybe it'll work as an anesthetic potentiator. [175:00] Meaning, if you gave some of this, you'd need to use less anesthetic, it would act like a catalyst. Because it tended to make you sleepy. If you read the leaflets on Dramamine, one of the cautions is it'll make you sleepy, don't drive. Why don't we give it to some surgeons and see if they can find a use for it? Literally, it's like that. and One of the people who gets that drug is a lieutenant in the French Navy, Henri Laborey. He tries it as an anesthetic potentiator, and he also gives it to some of the patients who are awaiting surgery. Normally, when you're awaiting surgery, you're a little bit anxious. These patients stop being anxious. This was the era of lobotomies, and he wrote to one of his He said, this works like a chemical lobotomy. These people don't care anymore about their surgery. And that's supposed to be a good thing, right? Well, lobotomy hadn't become the nasty word it would become in a few years. So one of his colleagues contacts Dele and Danica, who work at Sedan's, which is the biggest mental hospital in Paris, and says, hey, guys, this might work on your... Psychiatric patients, you should give it a try. And they do. When it doesn't work, they give a larger dose, and when it doesn't work, they have a large dose. And sure enough, Patients stop acting out. They stop smashing furniture. They're still sort of conscious, but they're less mobile and they're much calmer. And this is why in the early stages, chlorpromazine, which becomes known as logactyl or mighty drug in Europe and thorazine here, The hospitals see it as a boon because it'll help control the patients. They're not yet thinking of it as more than that. So that's the accidental one where it's discovered. It comes to North America via Quebec, where there's a psychiatrist up there, Hans Lehmann. who actually works in the Protestant hospital. Quebec in those days is dominated by its Anglo-speaking elite, who oppressed the French Canadians pretty mightily. But because of the French connection, he gets mounts of the drug. He's the one that does the early trials here, the early, I shouldn't say they're really trials. I gave it to 15 patients and they were like that. It's completely uncontrolled. Um, Roan Palankas had to sell... the rights to an American company. In those days, American physicians don't trust European science or European medicine. especially European medicine. So Rumpleinck sells the rights. The first two drug companies it approaches say, no, thank you. This doesn't look very interesting to us. I don't think there's much of a market. And then SmithKline in French buys it up. and within two years two million people are taking this drug it's a bonanza for them right not an accident because they put their best salesman on the job of selling this and they realize the hospital psychiatrist mostly aren't interested. They haven't yet gotten to this idea of a chemical cure or a chemical treatment. So it's the companies that wake up to this. The companies wake up. They sell it to the politicians. They go to the state legislatures. They have moving pictures of an agitated patient who turns calm. So this is already the mechanism of big pharma. And then, of course, once that's successful, it turns out that chlorpromazine can be easily tweaked as a molecule. And so copycat drugs emerge on the scene. So this happens in America in 1954. The following year in 1955, we get the so-called minor tranquilizers being invented and brought to market. This is Milltown. major television star of the mid-50s, Milton Byrne, who calls himself Uncle Miltown and promotes the drug heavily on his show. So these are mostly like tranquilizer type of effects? Those work really, they're muscle relaxant types of things. And, you know, later on in the 60s, we get Valium and Librium coming on, adding to it. [180:00] and replacing those first-generation drugs. So you have major tranquilizers, minor tranquilizers, and guess what? The Freudians don't want really anything to do with these drugs. The hospital psychiatrist, once they wake up to the usefulness of Thorazine and its analogs do start using the drugs a lot. And that's really important. And In the early 60s, they change their name. Instead of being major tranquilizers, they become anti-psychotics. So that suggests they actually attack the underlying psychosis. Is there any evidence of that? for them. They do change the forms of psychosis in important ways. Some good, and some they fail to attack. So, Um, They reduce the agitation. they are reduce... the delusions and the hallucinations, the things psychiatrists call the positive symptoms of schizophrenia, those they help with for... Not every patient, but for a significant number of patients. And that's very important. Why are they called the positive? The positive symptoms activate things. They activate the hallucinations and the delusions. Those are changing and they're visible usually because if somebody's deluded or hallucinating, you know about it pretty quickly, right? The negative symptoms are things like apathy, loss of ability to interact with people, lack of initiative. All of those things are devastating. Just to state out loud and clear that both positive and negative effects, so-called by psychologists of schizophrenia, are both devastating and both negative. Yes, yes. I think that's right. In the common parlance of what negative means. It's a very strange choice of language, but it's been there for a long time. So it's embedded. Now, to the extent that, Antipsychotics work. They work on the positive symptoms. They either dull them down, so you're still hallucinating a bit and you're still delusional, but it's not. It's very much less. You are somewhat pacified. You're less overtly disturbed. But the negative side of things, not so much, or not at all. Then on top of that, Um, The drugs work for some people and they don't work for others. And a significant number of psychotic patients that are non-drug responders, Just as a significant number of people with the depression are not responsive to antidepressants. Moreover, initially the enthusiasm for these drugs, everybody neglects the fact that they have serious side effects. Or, many of them argue, the side effects are an essential part of the treatment and you just have to put up with it. So what are we talking about when I say there are nasty side effects? Well, among others, you may become incurably restless. So you're constantly in motion, you're moving around, you're never still. If you're in the presence of somebody, Like that, it becomes unbearable after a fairly short while, and it's unbearable often to the person who can't control it. Other patients develop Parkinson's disease symptoms. It's an awful affliction, which unfortunately affects a significant number of people each year. And we don't have, we have through L-DOPA a means to delay its impact, but eventually that loses its efficacy. And unfortunately, we don't have a cure. So you have those. And then perhaps the nastiest is what's called tardive dyskinesia. Tardif, because it's late developing, it doesn't happen right away. And dyskinesia, because what involves is jerky, uncontrolled movements of the body, and particularly of the facial muscles. So your tongue will protrude, you'll make strange noises, you'll twitch, you'll stagger about walking. If somebody like that is walking down the street towards you, you will think. there's a mentally ill person and you're across the other side of the street and yes they probably are a mentally ill person but what you're seeing is the iatrogenic effects of the drugs they're on okay so that problem was ignored for about 20 years paper appeared in science by george crane and psychiatrist, in which he said, [185:00] We as a profession have been ignoring... this terrible problem. Yes, the drugs do some good. but they're also creating a lot of harm. And we need to focus more on that. And it took a few years, but by the 80s, I think the American Psychiatric Association was very worried by that problem. and The drug companies were kind of worried about it, but didn't have any obvious solution. Until towards the end of the 80s, something happened. In 1957, when the people were developing copycat versions of Thorazine, Clozapine was developed by a small company, which was subsequently bought up by a bigger company and introduced in Europe. It never came to America because of two things. First, it tended not to produce tardive dyskinesia. And at that time, many in the profession thought if you didn't get those symptoms, you weren't attacking the problem. right? Secondly, um, Thank you. In a significant number of patients, it destroyed the patient's white blood cells and they died. Okay, not a good outcome. So it was quickly withdrawn from the market. And it never made it to this side of the Atlantic. However, as this taut of dyskinesia problem became more acute, There was an attempt to revive... Clozapine. and It turns out it tends to work better in treatment-resistant cases, meaning cases don't respond to the other cases. antipsychotics that we have. And it could be revived, but at the cost of weekly blood Checks. because you had to be very careful. If your white blood cells count started to drop, you had to stop, right? So... It came to market in the late 80s, and Very quickly, other drug companies tried to find other compounds... Actually, I don't know. chemically not related to it, but that's hardly the point. The whole class of drugs became known as second-generation antipsychotics. So, clozapine, risperdal, zyprexa. Zyprexa. Zyprexa. Yes. And so, there were a number of these, and they have actually, because they are chemically quite different from each other, but they're classed together in the public mind and in the professional mind. They tend to have different side effect profiles and slightly different modes of action and differing levels of efficacy, I think. Of course, there's not a real, at that time, or even now, a real science of like when you have a human come to you, what is the actual protocol once the drugs revolution came along, increasingly the studies were funded by the drug companies who owned the data and controlled the data and only released what they chose to release, what was helpful for them and not what wasn't. And there were heavily marketing stuff. Oh yeah, very heavily. And then to get FDA approval of efficacy and safety, you need to two trials. You might have conducted 15 trials and 13 of them had been failures, but if you had two that worked, that was enough. That's what you needed. That was the gold standard. So 2005, the National Institutes of Mental Health funds a drug study, not an industry study. What it wants to look at, the first generation drugs are now out of patent and they're cheap. and are quite expansive. 10 times as expensive in some cases. So we do something called the Cady Study, and it's published in the New England Journal of Medicine. And there are two Interesting findings. So you have one first generation antipsychotic, one of those very early drugs, and you have four antipsychotic. More recent drugs. that you're looking at. And you ask a number of questions. Are the new drugs more efficacious than the old drug? No. Hmm. Were patients... willing to tolerate these drugs. And that was a finding that I thought was much underreported at the time. Between 67% and 82% of the patients, depending on which drug they were on, dropped out of the trial because it [190:00] that the drug wasn't working or they couldn't stand the side effects. So that tells you these are our best drugs. You know, they're real complications here. Then, as we delve further into it, do they have nasty side effects? Well, less tardive dyskinesia, somewhat but a whole new set of side effects if you take These pills. you will gain. In most cases, a lot of weight. 10, 20, 30, 40 pounds, 50 pounds. What does that do? That goes. Gives you metabolic syndrome, it gives you diabetes, it gives you heart trouble. So, you Important to state, when we're looking at this, because *sniff* There is no free lunch. with medicine. If you take an aspirin, it may cause your stomach to bleed. sometimes enough to really put you in serious jeopardy. Most of the time it's fine. um, Everything. every drug that's brought to market. has, the main effect we're looking for and some side effects which may be minimal for most people, but for some people maybe worse than that. So, We've got to, it's one of these cost-benefit analysis, right? You're getting some relief from your business. psychological psychiatric symptoms but you're courting these other dangers that may or may not are and going in we don't know where you're going to fall. We don't know. trial and error. You mean every individual that walks into the picture, they don't know where in the distribution they fall? Right. And we have no biological markers at the moment that would tell us. One or two of my friends in the psychiatric genetics industry, if that's the right term for it, but in that research area, are saying, well, we haven't done very well to find the genetic patients are going to respond well to drugs and which will, which shouldn't be given them because they're not going to. That's a promissory note. It's not something that they actually can do now. It's just we hope we'll be able to do this, and I hope they're able to do it too. But, you know, you can't have an enormous amount of confidence in that. Maybe it'll happen, or maybe some other mechanism will emerge that allows us to see who the responders and non-responders are, who's going to suffer the worst side effects if they're put on these medications. And the side effects do vary. Though a lot of what I've described is common to this class of drugs. And sometimes it's hard to describe the side effects. You're talking about the human mind. Yeah. So describing the side effects, it's not like bleeding or like diarrhea or weight gain. That's describable. But like the effect on your personality? Yeah, that's much harder, much harder. People, you know... Some of the patients who drop out, drop out because they find the richness of their mental life is completely gone, and they don't want to tolerate that. They'd sooner tolerate some hallucinations. That's a hard one. So there's that picture, the SSRIs that also came to be Prozac, Zoloft, Paxil, all of that. Well, again, they're the second generation of antidepressants, so... That's a complicated story. Again, it's an accident. They're treating patients with advanced tuberculosis in the 1950s. Now, that's a very unpleasant thing that's also going to kill you. So tuberculosis, very advanced cases, you're coughing your lungs up, you're depressed as all get out. And here we have two new drugs, iproniazid, that we can use that maybe will treat the tuberculosis patients, start acting happy, dancing about. Their mood changes. Bingo. We've got something that maybe we can use over here to treat depression. Yeah. However, the drug companies in circa 1960 think of depression as a small market, because what they're talking about is the kind of melancholic, psychotic depression that leads people into the mental hospital. And that's not an insignificant group, but it's not a huge group. So it's really much later on that things begin to change. Right now it's fair to say depression [195:00] is the common cold of psychiatry. It's you know, it's, It's abundant. The depressive diagnosis is probably the most commonly given one among psychiatrists. So part of that is a deeper understanding of the human mind, and a big part of that is probably the drug companies convincing the world. Well, it's transforming, yes. So there were big disputes, for example, when DSM-5 was being contemplated about whether grief happened. bereavement would count as a mental disorder, count as a form of depression. If you... lose a parent, if you lose even worse a child, um, It's a. deeply, how can I put it, deeply upsetting? Yeah, it's one of the most horrible things that can happen to you. Yes, exactly, as I unfortunately know from personal experience. So, um... If you're feeling emotionally pretty wrought in the aftermath of an event like that, does that mean you're mentally ill? Does it mean you need an antidepressant? Well? Some psychiatrists say yes and some no, but it's an example of what happens in psychiatry repeatedly, what I would call diagnostic creep, which is a term actually an Australian named Nick Haslam came up with. But it's a phenomenon I described before that. You start with a core of anxiety. unambiguous deviations from the norm that are so serious that any competent member of the culture knows that's that. But Then you begin to say, well, there's this penumbra you see, and just outside that core, there are people who are also disturbed, not perhaps as sufficiently disturbed that you actually recognize it, but it's happening. And so that has tended to happen over and over again. Parents with an autistic child won't necessarily agree with what I'm about to say, but the chief editor of DSM-IV, Alan Francis, is convinced the huge increase in the number of diagnoses of autism is more driven by the fact he loosened the criteria for the diagnosis than it is because there are more actual cases. Autism used to be a fairly rare phenomenon, and now, sadly, it's a very broad one. why parents react very negatively to that because the diagnosis is the key to all sorts of social supports and educational supports and all the rest. And they're dealing with a child who is extremely difficult. But there is a real difference between the most severe forms of autism where people lose the capacity to speak and very often any ability to interact with other people and so that are of a still serious but milder sort. Diagnostic creep is not driven just by psychiatric imperialism, the desire for more territory, more patients. It's driven as well by by patients and people and they resist it being pushed back very often. So families have formed organizations like NAMI, but those aren't the mentally ill. Those are the family members of the mentally ill. And there are differences in the perspectives and the interests of the family members and the patients. And that's easy to forget. I think one of the things you talk about is, I mean, the quote you had was used the word mental health maladies, if you're suffering from them, it's a deeply lonely experience. And then if you're around somebody suffering from it, it's a very social experience. Yeah, this is actually, that's a paraphrase of, I was quoting one of my friends and fellow historians of psychiatry, Michael McDonald, the most solitary of afflictions for the sufferer, which you can see that very powerfully. And that's why I think there are a ton of people who suffer in various ways from mental disturbances of one sort and another. But the effects aren't confined to them. they extend out to everybody else around them. And that's really powerful. So, We had this first generation, and there were actually two different kinds of antidepressants, MAOIs, as they're called in the trade, and tricyclates, which were called tricyclates because they had a third ring of a certain element in their molecule. [200:00] Those had... as I say, a limited market, but also there were complications associated with them. It was easy to overdose and die. And so giving a depressed patient a bunch of pills that if they took too many of them would kill them was tricky. They also could kill you another way because, for example, you couldn't, certain dietary exercises, Items. Cheese. cured meats in combination with them were were very very health-friendly It may be even fatal. No. In the late 80s, The drug companies came across a new class of antidepressants that didn't have those side effects. As we'll see, they had other side effects, but not those. And the most famous of those was Prozac. There were a class of drugs called SSRIs. And again, forgive the acronym, but what it means is selective serotonin reuptake inhibitors. Serotonin is something manufactured in our bodies, actually in our digestive system, and it performs a variety of functions in the body, but it's also one of the neurotransmitters in our brains. the way these drugs worked was by um slowing the reuptake of serotonin in the brain, which was... marketed by the drug companies as the solution to depression. That when you got depressed, it was because you didn't have enough serotonin in your brain. And these pills solved that problem. It was like, well, Tipper Gore, Al Gore's ex-wife, was like many politicians' wives, depressed for reasons I fully understand, or at least partially understand. And she went And that was one of the things she was given. And she became one of the big public advocates for SSRIs, which still were the most prescribed antidepressants. Do they work? And what are the side effects? Yeah. So here's where we get into slippery territory. Every time you do a controlled study, of these antidepressants. They beat placebo. in a statistically significant margin, but not necessarily in a clinically significant margin. And this is when you see drug ads. Be very careful. This one significantly improves X or Y. Does that mean clinically or does it mean statistically? Because the fact if you when we measure improvement with depression, we tend to use rating scales of various sorts. And if you improve on one of the major scales that's used by one or two points on a 60-point scale, it may be enough to show statistical significance. This drug is a little better than placebo, but it doesn't really affect your quality of life much. And for most patients, antidepressants are marginally better. the placebo, but a lot of the effect is the placebo effect. And they come with very difficult side effects. A lot of people describe them as numbing drugs. They flatten everything out. So you can't experience the highs and lows that normally we take as part of human experience. And then the numbing extends elsewhere in your body, in particular, lots of patients find a complete loss of libido. They're they can't get an erection they can't climax if they're a woman their sex life just goes away and sometimes it doesn't come back after you stop the drugs next layer of problems getting off the drugs for some people turns out to be hell on hell on wheels uh they get worse depression than they had before they get a feel terrible feelings their brain is sparking something's wrong um And so many patients find themselves trapped on those drugs for a long time, and we don't know what the effects of that are going to be. So it's a very mixed picture. You know, that's why I think, Groups like NICE in England are saying, Use CBT as the first line, not drugs. um But again, it's also fair to say, I think what we find, and there was a recent [205:00] Lancet study that I think was revealing on this point. It's like this with both antipsychotics and antidepressants. You have a group of people who respond pretty well. And the side effects for them are bearable, or even they don't experience them. That's great. You have a group of people and it's significant. With depressed patients, we're talking 40 or north of 40% who aren't responding. Okay. I'm sorry. So drugs aren't doing anything for them, and they're running a risk. And then in the middle, you have a group of people who get some positive feedback. improvement, but they also get side effects. And that's where you know, this cost-benefit analysis, if we can call it that, comes into play, and it's very difficult. And the problem is going in, you don't know which group you're going to fall in, and your doctor doesn't know which group you're going to fall in. And more importantly, one of the things that drugs revolution did. was it moved... the diagnosis and the prescribing of things away from psychiatry alone. So many of these things, particularly antidepressants, are dispensed by primary care docs, not psychiatrists. Let's zoom out. We did say that there's a real crisis. from an individual perspective, suffering from psychosis or suffering from depression. Uh, what, are you supposed to do? What works? And what is the hope for the future in the next 10, 20, So you... Probably need to try the drugs because... The suffering is very intense, but you need to be aware of things and you need a clinician who's monitoring very carefully. More generally... Psychiatric research needs to broaden. We have spent our monies On. Drugs on neuroscience. and on genetics. But there are other things we could do that would improve the lives of families and patients more immediately. So we need to spend some time on the psychosocial dimensions of mental illness and to allow psychiatrists to build careers in those fields. One of the problems, if you're an academic psychiatrist, you're Hó. future is dependent on you bringing in Grant monies. And there aren't grant monies available to study. Are there better ways we could cope with the problem of homelessness? Are there better ways we could make ease the problem for families who are having to cope with somebody in their midst who's hallucinating? That sort of thing, I think, would help. What about talk therapy on both the CBT, cognitive behavioral therapy, and psychoanalysis? We left psychoanalysis in this place where society left it behind. I think it's become a niche product now. Only the very wealthy can afford to do it, and some of them indeed do make use of it, and some of them claim that it helps them. Do you think there's future in it? I will add an extra bit to that carefully is with the advent and the rapid improvement of artificial intelligence systems that are able to... Communicate. with individual humans and learn a lot about them and have a conversation about the deepest secrets that you sometimes actually would even be uncomfortable telling even a therapist that starts to go uh into the realm of freud and young and psychoanalysis yes and we did see um actually coveted with the isolation that it produced and the fact people couldn't go to their therapist directly, we did see the rise of some of this change distant. learning of this, and some of it may indeed be mechanizable in the way you described. It's very important that psychiatrists, broaden their perspective on these things, and some already have. I think public policy is in a mess when it comes to serious mental illness. But I'm pessimistic about fixing that, because it would cost bunches of money. If we were talking about something where we could Cure people. transform them from, as they used to say, tax eaters to taxpayers, they'd be incentive. [210:00] to do it. But the honest answer is right now, that's not where we are. And so we've faced dilemmas. I think helping people as much as we can with social supports and You know, Social interaction is tremendously important to people's mental health. If they lack it, if they're lonely, if they're isolated, it does bad things to people. So, Somehow providing that kind of support, providing some sense of agency to people who often lack it, would be very helpful. I hope somebody has a breakthrough and produces a better drug because unlike some people, I would be astonished if the major forms of mental illness didn't have a biological component to them. I don't think that's ever going to be the whole story, but it's going to be an important part of the story. And therefore, the fact that major drug companies have abandoned research in this And the fact that there's no research being done by the people with the most money to develop better treatments is, well, one word for it would be depressing. That's not what we want to see. So the path forward is a mix of continued research on drugs. But from a patient perspective, extreme caution in use of those drugs. Yes. Talk therapy, whether it's CBT or psychoanalysis, further investigation research on that front. Then the psychosocial component of social family, people around you, less loneliness, investigating how from a cultural, social perspective and from a public policy perspective, have, and all of that together. Yes. And break through with people who have very hard time making those connections, or who've lost the ability to make them. If we can zoom out, looking back at this rich history of human beings, And we did look at the darkness, but I think there's a very large number of people... that want to help those who suffer. So looking at the data, At the history of people trying to figure out how to help those who suffer. What gives you hope about our future? A real hope for the future of psychiatry that we can actually help people who suffer. *sniff* Well, I think... We have... a profession with many Thank you. Very well-meaning people. who see the suffering on a day-to-day basis. face-to-face basis. And I like to think that among them will be people who move this thing forward. And the fact is, we have moved things forward. We have tended to dwell a lot on some of the very unsavory aspects of the past, and even some of the drawbacks of what we have available to us Times... highly motivated people have been able to do very good things to help people with these conditions. And there is, I think, hope in the future that we will see more of that than has been the case. technocratic kind of direction and less reliance on something as simple as giving people pills, because that can help, but it's clearly not going to be the solution to the whole thing. We need a system that is... aware of and catering to the suffering that people experience and finds ways, if they can't eliminate it entirely, to ameliorate it in ways that people will sense is actually of help to them. It's a very difficult area, this one. It's one that... touches some of the most profound aspects of our experience, selves as human beings. And I think as difficult as this problem is, it's very important not to be cynical, not to give up hope, not to deny the possibility of progress, because that's all [215:00] there and has happened and I hope will happen with increasing pace in the years ahead of us. And if you're listening to these words and you're right now in this moment of your life where you yourself are suffering, Please no. were with you. We're in this together. Stay strong. There's hope. but Jeremy as one human to another. I love you, brother, sister, if you're listening to this, stay strong. Andrew, thank you for this incredible work of history that you do, incredible work of raising awareness, stepping into a difficult topic and trying to find the wisdom, the insights in it. And thank you for this incredible conversation today. Lex, thank you for having me. I felt you were remarkably prepared to push me in various directions. So you'd obviously done a lot of preparation to get this in the right frame. And I hope that people will get something positive from this conversation, along with some of the darkness we've inevitably had to talk about. Thank you for listening to this conversation with Andrew Skull. To support this podcast, please check out our sponsors in the description, where you can also find links to contact me, ask questions, give feedback, and so on. And now, let me leave you with some words from Friedrich Nietzsche. to live, is to suffer. To survive is to find meaning in the suffering. Thank you for listening. and hope to see you next time. you