The Rise and Fall of the Age of Psychopharmacology
EDWARD SHORTER, PHD
Professor of Psychiatry, Professor of the History of Medicine, Faculty of Medicine, University of Toronto
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Library of Congress Cataloging-in-Publication Data
Names: Shorter, Edward, author.
Title: The rise and fall of the age of psychopharmacology / Edward Shorter. Description: New York, NY : Oxford University Press, [2021] | Includes bibliographical references and index. | Identifiers: LCCN 2021016419 (print) | LCCN 2021016420 (ebook) | ISBN 9780197574430 (paperback) | ISBN 9780197574454 (epub) | ISBN 9780197574461 (Digital-Online)
Subjects: MESH: Psychopharmacology—history | Psychotropic Drugs—history | Drug Industry—history | Mental Disorders—drug therapy | Drug Development—history | Physician-Patient Relations | History, 20th Century | History, 21st Century | United States Classification: LCC RM315 (print) | LCC RM315 (ebook) | NLM QV 11 AA1 | DDC 615.7/8—dc23
LC record available at https://lccn.loc.gov/2021016419 LC ebook record available at https://lccn.loc.gov/2021016420
DOI: 10.1093/med/9780197574430.001.0001
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In memory of Barney Carroll
Don Klein
Mickey Nardo
PART II: WORSENING
Preface
The Lord hath created medicines out of the earth; and he that is wise will not abhor them. —Ecclesiasticus, 38:4
As I was at the Y talking to my buddy, who is 55, he reached for a pill bottle, took out a 2-mg tablet of Abilify, a psychiatric drug, and swallowed it. “This has changed my life,” he said.
By 5 pm each day he used to storm around ready to hit someone, loud, full of fury, and he experienced several arrests and an inability to keep himself from yelling at the cops. Now, he says, “This has given me my life back. I’m normal again.”
So, treating mental illness with drugs—psychopharmacology—really can work. The drugs are often highly effective.
But what did my friend have? Mania or hypomania? He wasn’t euphoric, had no flight of ideas, no hyperactivity, and certainly no psychosis. He was just chronically angry and agitated. That’s not in the DSM, the diagnostic bible of psychiatry. And chronic anger is not one of the official indications for Abilify either, which was launched as an “antipsychotic.” Abilify is now also indicated for “bipolar disorder.” My friend had neither psychosis nor bipolar disorder. Yet, his clinician had the good judgment to prescribe the drug.
So, in my friend’s case, psychopharmacology was effective, but the official side of it—diagnoses and treatments—was nonsense.1 This is not the way medicine is supposed to work. People still take drugs for the brain and mind that often work, but the science has gone out of it. Neither the diagnostics nor therapeutics of psychiatry today may be said to have a scientific basis. The idea that you are better because Prozac has somehow restored your level of serotonin is just baloney.
There have been many books on how the pharmaceutical industry has taken over academic psychiatry, but what interests me is how things have declined over the years, from the relative dignity of the arm’s length relationship between industry and the academy in the 1960s, to the invasion and capture of academic psychiatry by industry in the 1990s and after. How did this decline happen? Nobody has written about that.
I am not belittling the studies documenting the parlous state of affairs today. These are written by investigative reporters and indignant scholars who have done their homework, and what they say is sadly true. But how about the status quo ante? Was it equally bad, or was there some kind of “Golden Age”? I am
x Preface
deeply suspicious of Golden-Age rhetoric, as it usually reflects a nostalgic smear of Vaseline on the rearview mirror. But medical ethics do tend to crumble under the pressure of the profit motive.
The rise of psychopharmacology was a brilliant scientific event. Its fall has resulted from the triumph of commerce over science. These have been among the most important events in medicine—and in people’s lives—over the last half century. Millions of Americans take psychiatric drugs, and patients have been given such ersatz diagnoses as “major depressive disorder” and “adult ADHD,” which have made mental semi-invalids of them. This is not a victory of science in psychopharmacology. It is a perversion of science in the interest of commerce.
The story of the successful treatment of madness has been very positive, and we should not forget that as we navigate the tangle of scams, jury-rigging, and distortion that lurk beneath the surface of the field. Alec Coppen, a pioneer in British neuroscience who practiced at West Park Hospital for many years, told David Healy in 1996, “People today don’t realize what a tremendous impact the antidepressants, neuroleptics and lithium have had on the terrible morbidity of mood disorders and schizophrenia. . . . When I go to West Park now I find about 400 patients suffering from dementia. What a contrast to forty years ago, when there were 2,000 very disturbed young and middle-aged patients, many of whom are now leading ordinary and rewarding lives thanks to these advances.”2 This is worth something.
Abbreviations
ACNP American College of Neuropsychopharmacology
ADAMHA Alcohol, Drug Abuse, and Mental Health Administration
ADHD Attention-deficit/hyperactivity disorder
AIC Academic–industrial complex
AMA American Medical Association
APA American Psychiatric Association
CDER Center for Evaluation of Drug Research
CINP International College of Neuropsychopharmacology
CME Continuing Medical Education
COMT Catechol-O-methyltransferase
CROs Clinical research organizations
CSR Corporate social responsibility
DBSA Depression and Bipolar Support Alliance
DESI Drug Efficacy Study Implementation
DHEW Department of Health, Education and Welfare
DSM Diagnostic and Statistical Manual of Mental Disorders
DST Dexamethasone suppression test
EBM Evidence-based medicine
ECDEU Early Clinical Drug Evaluation Unit
ECNP European Congress of Neuropsychopharmacology
ECT Electroconvulsive therapy
EEG Electroencephalography
EKS Expert Knowledge Systems
EPS Extrapyramidal symptoms
FDA Food and Drug Administration
FGAs First-generation antipsychotics
GSK GlaxoSmithKline
HARKing Hypothesizing After the Results are Known
ICI Imperial Chemical Industries
IITs Investigator-initiated trials
IND Investigational new drug
IRB Institutional Review Board
KOLs Key Opinion Leaders
LSD Lysergic acid diethylamide
MAO Monoamine oxidase
MAOIs Monoamine oxidase inhibitors
MBM Marketing-based medicine
MECCs Medical education and communication companies
xii Abbreviations
MRC Medical Research Council
NDA New Drug Application
NIH National Institutes of Health
NIMH National Institute of Mental Health
NNH Number Needed to Harm
NNT Number Needed to Treat
OCT Office of Clinical Trials
PDAC Psychopharmacologic Drugs Advisory Committee
PDR Physicians’ Desk Reference
PhRMA Pharmaceutical Research and Manufacturers Association
PHS Public Health Service
PI New York State Psychiatric Institute
PSC Psychopharmacology Service Center
PSSD Post-SSRI sexual dysfunction
QEEG Quantitative EEG
RCTs Randomized controlled trials
RDC Research Diagnostic Criteria
RDoC Research Domain Criteria
SAMHSA Substance Abuse and Mental Health Services Administration
SDA Serotonin-dopamine antagonist
SGAs Second-generation antipsychotics
SKB SmithKline Beecham
SKF Smith, Kline & French
SNRIs Serotonin-norepinephrine reuptake inhibitors
SSRIs Selective serotonin reuptake inhibitors
STI Scientific Therapeutics Information
TCAs Tricyclic antidepressants
TD Tardive dyskinesia
TMAP Texas Medical Algorithm Project
VA Veterans Administration
VNS Vagus nerve stimulator
WBSTs Worldwide business strategy teams
WHO World Health Organization
WSJ Wall Street Journal
Y-BOCS Yale-Brown Obsessive-Compulsive Scale
Introduction
Psychopharmacology . . . is compelling chemistry, for the first time, to look behavior in the face.—Joel Elkes (1965)1
John M. (“Mickey”) Nardo, in his retirement, practiced psychiatry in a volunteer clinic in the Appalachian hills of Georgia. “I worked in the clinics today,” he wrote in 2012. “In the morning, I saw adults—a lot of them. I had three patients where the central issue was unrecognized antidepressant withdrawal syndromes. I had three patients who’d been told they were ‘bipolar’ (who weren’t).” But the high point of the day came that afternoon. His last patient was an adult woman “with persistent PTSD from a terrible event eight years ago that involved the death of her son. The tension of undoing bad diagnoses and bad treatments all day just disappeared as I talked to this woman about her illness. I felt like a doctor instead of someone putting out brush fires, a case-worker in a social agency, or a med-check doctor.”2
There are, said Nardo, plenty of psychiatrists out there, “doing what I did, trying to help people with their mental illnesses, the systems they have to negotiate, their misdirected treatments, their iatrogenic symptoms, their medications . . . and sometimes even those afflictions of the mind brought on by life experience in childhood and beyond.”3 There are many such clinicians. This book is not about them.
This book is about the physicians who created the mass use of antidepressants and antipsychotics and the industry that whispered in their ears. In the United States in 2015 to 2016, almost seven adults in ten (69.0%) had used a prescription drug within the past 30 days. In adults 40 to 59 years old, the most frequently used drugs were antidepressants (prescribed to 15.4% of the entire population in that age group).4 This means that if you go to the supermarket, one in seven of the middle-aged shoppers you encounter will have taken an antidepressant within the past month. In other words, a seventh of your fellow shoppers are “depressed.” Moreover, almost all of them (84.3%) have been taking their antidepressants long term.5 Nardo was amazed to find that his poor workingclass patients were all on prescription drugs. He was familiar with the statistics I’ve just cited. “All of this has happened in a period where psychiatry has been
telling itself that it’s medicalizing, but there’s nothing about those figures that’s medical.”6
An Age of Psychopharmacology? Yes, indeed, because psychopharmacology turns out to be as much a cultural concept as a medical concept. Treating patients with psychoactive drugs has always been with us. There is nothing wrong with this. Psychopharmacology means investigating systematically the different effects of drugs on different mind and brain diseases. This, too, in unproblematic. But the “Age of Psychopharmacology” implies that an entire medical culture, indeed a whole popular culture, has been wrapped around a concept so that it has become an “age.”
Psychopharmacology was a kind of cultural style within neuroscience. Soon abducted and corrupted by industry, it ceased to be a rigorously scientific discipline of its own, becoming instead a commercial trope for selling drugs. Wideeyed speculations about neurotransmitters and receptors and jury-rigged drug trails replaced scientific evidence.
Yet, psychopharmacology was not entirely unscientific: Important questions about the impact of pharmaceuticals on the brain were investigated and in some cases resolved. But in retrospect there was an Age of Psychopharmacology, comparable to the Age of Anxiety or the Age of the Railroad. A culture of psychopharmacology arose in the 1950s and 1960s, and today it is dissolving.
In making this case, I often quote Mickey Nardo (and, yes, I refer to him by his universal nickname, Mickey). He was a psychiatrist with earlier training as an endocrinologist, who was on the faculty at Emory University for years, then in private practice in Atlanta. After Atlanta, he retreated to the hills of Appalachia in Georgia, where he volunteered his time in a local charity clinic and wrote a blog, “One Boring Old Man,” which is among the most productive sources for this period—from roughly 2011 to his death in 2017. He was a kind of James Boswell acting as a chronicler to the latter-day Samuel Johnson, who in this case was Bernard (“Barney”) Carroll, one of the great scientific figures of late twentiethcentury psychiatry. Carroll led the Mood Disorders Unit at the University of Michigan for years, then was chair of psychiatry at Duke University, then moved to California to compose his own blasts against the “Key Opinion Leaders” (KOLs), a synonym for what he and others perceived as the sell-outs of today’s psychiatry.
A theme: The last 30 years have witnessed the degradation of psychiatry as a clinical discipline. The two great arms of medicine are diagnosis and treatment, and the psychiatric diagnoses in the DSM (Diagnostic and Statistical Manual of Mental Disorders) turn out not to correspond to real diseases at all. The treatments are mainly ineffective (the SSRIs), or effective but toxic (many of the antipsychotics) and inappropriate in patients.
One problem is that psychiatry has been devoured by “depression.” The only two adult diagnoses left standing are depression and schizophrenia. You don’t need an MD degree plus 4 years of postgraduate training to say, “You’re depressed” and prescribe Prozac. A garage mechanic could do it. A comparable degradation has happened to no other medical specialty. Psychiatry is unique.
Mark Kramer, head of clinical psychopharmacology at Merck for 13 years (between 1989 and 2002) put this failure of science in slightly different terms: The real problem, he said, is “that in one half century the best minds have not provided a compelling pathophysiological basis for most people with stereotypic syndromal phenotypes who are flagrantly disabled.”7 In other words, in the “show-stopping” illnesses of psychiatry, such as chronic social withdrawal (“schizophrenia”), psychotic depression, melancholia, and catatonia, we still have no idea what is going on. These are all disabling illnesses. It is said that in medicine that only illness worse than psychotic depression is rabies. But what happens in the brain to produce this degree of disablement is still entirely unclear.
I am scarcely the first to have chronicled this discouraging progression from decades of discovery and excitement to the pall of corruption and stagnation that latterly has beset us. Barry Blackwell, a pioneering psychopharmacologist (he discovered the “cheese effect” in the monoamine oxidase inhibitors), contrasted the “Pioneer Era” of the years 1940 to 1980 with the “Decades of Stagnation” of the years 1981 to the present.8
I realize that this critical approach skirts nihilism, as though psychiatry were bankrupt as a clinical discipline and ineffective in office practice. No! This is not the impression I wish to convey. Many psychiatrists are highly effective as healers, and this is for two reasons.
One is that the old hands do develop a sense of which drugs work on which patients. The official indications and diagnoses are rarely helpful, but experience speaks volumes, and the feeling that an unhappy and agitated patient might respond to a drug initially marketed as an antipsychotic is what clinical experience is all about.
Second, in psychiatry the trust built up in the doctor–patient relationship counts for a lot. Hungarian psychoanalyst Michael Balint called this the doctor using him- or herself as “a pill.”9 And there is a good deal of evidence that the personality and commitment of the physician make as much difference as the medication that he or she prescribes.10 The resources of psychopharmacology, if they work at all, may well be secondary. Mickey Nardo reminded us that, “At its core, the patient–physician relationship involves a mutual commitment between a patient and her physician to her own well-being. We psychiatrists call this the therapeutic alliance and have plenty of evidence that it is the source of healing.”11 Roger Greenberg, a psychologist at Upstate University Hospital in Syracuse, attributed the small therapeutic success of the “antidepressants” to this
doctor–patient relationship: “Creating a strong collaborative treatment alliance with a clinician who is viewed as caring, empathic, open, and sincere augurs well for a positive outcome. . . . These qualities are as important for patients receiving drugs as they are for those involved in psychotherapy.”12
It is the therapeutic alliance that is part of the secret of effective healing in psychiatry, the deep intrinsic confidence of the patient that, in these skilled hands, he or she will get better. Psychopharmacology, if anything, detracts from this intrinsic power of the doctor–patient relationship. Yet many of the drugs are effective, and in serious illnesses, life without them can be a horror story.
The Big Picture
After the Second World War, the scene shifted from the Old World to the New World. Europe, in ruins, dropped out of the forefront of research, and the Continent not only was strapped for funds, but also had lost its Jewish investigators and clinicians, who previously had often been its most brilliant scientists, to New York and Los Angeles. The New World swung into leadership because Washington had money for pricey equipment, such as PET scanners, and for large trials. Heinz Lehmann, who left Germany in 1938 as a young MD to migrate to Canada, said, “I think that’s where America has stolen the edge.” “German medicine,” he said, “was an impressive thing and there’s no doubt about it. When we all went away [meaning the Jews], I don’t think this tradition was transferred to America, but it was abolished in Germany.”13 For a few brief decades, the United States was the legitimate world leader in psychiatry. The 1950s were the golden age of drug discovery, and although the drugs were not necessarily discovered in the United States, they were developed there and were turned into successful commercial products.
By the 1970s, the old psychoanalytic psychiatry was stumbling toward the tar pits. Freud’s doctrines, the backbone of Main Street psychiatry, had started to encounter widespread disbelief. Likewise, the old custodial psychiatry was doomed. The asylum, which previously had been the epicenter of biological thinking in psychiatry, was rapidly being dismantled.
A new psychiatry lay in its hour of birth, incorporating the huge advances in drug treatment that had occurred since the 1950s, but creating as well new thinking about diagnosis. The hope, largely unfulfilled, was that the new treatments would turn out to be specific for new diagnoses, and it was around diagnosis that the new psychiatry of the 1970s and after coalesced.
At the beginning, there were such hopes! In testimony before the Senate in May 1958, Nathan Kline, who had a private psychotherapy practice on Park Avenue and directed research in the New York State asylum at Orangeburg, said
he hoped that psychopharmacology would pass from “the correction of mental aberrations” to “improving the functioning of healthy individuals, which I think is the next great step to be taken after the present one.”14
Then the successes largely came to an end. Older psychiatrists like Nardo were often astonished at the deterioration of the field they were once so proud of. These men and women typically began as young clinicians and scientists in the 1970s, full of excitement about the ability of psychiatry to actually relieve the suffering of patients with severe illnesses and thrilled at shoving off from the psychoanalytic wharf. Then the savor of the moment turned to ashes as the useful drugs were abandoned for mediocre patent-protected ones, and the discriminating diagnoses—such as melancholia—were abandoned for such gross catch-alls as “major depression.” Yet most of all, what astonished the veterans of another era, of a golden age, was how industry invaded the field, turning many colleagues from reflective clinicians into shills. The term is not too strong. The toxic term “Key Opinion Leaders,” or KOLs, came to characterize many of the most prominent figures in the field as sell-outs.
There have been two derailments.
One is the DSM calamity, which began in 1980 with the DSM’s third edition. The sturdy classical diagnoses of yore, many of which really did “cut Nature at the joints,” as they say, were replaced by the DSM confections, a monstrous compilation of artifacts and half-diagnoses.
The second derailment was that the therapeutics of the years before 1970— which included some highly effective drugs, such as the amphetamines, the benzodiazepines, the classical “tricyclic” antidepressants, and such all-purpose agents as chlorpromazine (which was later defined as an “antipsychotic”)—have been replaced by the less effective but relentlessly marketed SSRIs and “secondgeneration” antipsychotics.
These first two derailments are perhaps remediable. But a third, which may be harder to turn around, was the destruction of the field’s intellectual autonomy after the invasion of the pharmaceutical industry.
Despite this intellectual disaster, psychiatrists remain highly effective as clinicians. So, this is where psychiatrists stand: their medications are, at best, nonspecific feel-good agents and, at worst, placebos. Their diagnoses are an inchoate hodge-podge of meaningless labels. Thus, wherein lies the secret of psychiatry’s success? It is largely in psychiatrists’ one-to-one relationship with their patients, the therapeutic alliance. And there is a good deal of evidence that this alliance is the main source of healing. Robert Cancro, a resident at Kings County Hospital in New York in the late 1950s, was treating “a severely regressed psychotic young man” who would come to their sessions, turn his chair away, “and stare into space with a silly smile on his face, and talk in a totally disorganized fashion.” It wasn’t
evident to Cancro that the patient was even aware of his presence. Cancro found the exchanges “meaningless.”
One afternoon, the patient
told me that the “medication” was helpful [he was in a trial], but that he really looked forward to “our little talks.” I was stunned. How could he look forward to “talks” that had no theme, started no place, and went nowhere? It began to dawn on me that he valued the human contact, despite my inability to comprehend the nature of the contact. I then had a further revelation that it took him over an hour and several bus transfers to get to the clinic. He paid a high price for that brief human contact, and obviously valued it more highly than I realized. The lesson of all this was that being a psychiatrist meant being a healer. Healing involved not only medication, but the relationship.15
This one-to-one relationship is precisely what makes psychiatry different from neurology, although in theory both treat brain illnesses. As Nardo put it in 2014, what separates psychiatry from neurology is the “interpretation and ‘making sense’ of the personal struggles of our patients. When we put the word ‘mental’ in front of the word ‘illness,’ we are demarcating a territory of human suffering that has issues of meaning at its core.”16 This is a noble enterprise: helping suffering humankind to come to grips with the meaning of their suffering, and to hope that restoration may eventuate through understanding the circumstances that have made them ill, rather than through Prozac. This approach will not work with the show-stopping illnesses, such as catatonia and psychotic depression. Yet most patients do not have these illnesses; they have vague and nonspecific feelings of demoralization, fatigue, anxiety, and not being at ease in their skin as a result of their life circumstances. This is called “dysphoria.” Here, meaning is everything. Will medications and DSM-style diagnoses help us here?
Two Cycles
Psychiatry has always been buffeted by “cycles.” Sometimes, the dominant paradigm changes quite dramatically, as in the shift from psychoanalysis to biological psychiatry, and sometimes the shift creeps in on little cat feet, as it did in 1850 in the world of Samuel Woodward, former superintendent of the Massachusetts State Lunatic Hospital. He noted that treatment was turning away from “depletion” (bleeding), from external irritants, drastic purges. and starvation. Instead, coming in now were “baths, narcotics, tonics, and generous diet.” “Not less to be appreciated in the improved condition of the insane,” he said, “[is] the change from manacles, chains, by-locks and confining chairs to the present system of
kindness, confidence, social intercourse, labor, religious teaching and freedom from restraint.” How salutary, he thought, that in this “age of improvement,” the lot of the insane should have been so improved.17 Thus did one cycle end and another begin.
The long view shows that there are causation and treatment cycles. In causation, the nineteenth century once had, as Ralph Gerard put it in 1956, a fascination with “material causes of psychiatric disorders. . . . With the advent of modern ‘dynamic’ views in psychiatry, the pendulum swung in the other direction; sociological, psychological and interpersonal factors in the etiology of mental disturbance were much emphasized. Now the pendulum is swinging back a bit toward the importance of material biological factors.” Indeed, Gerard said there had been a bit of an “overshoot.” “We have all wished mental disease to be determined mostly by sociological causes, because this situation seemed more hopeful from the therapeutic standpoint. If the individual had been broken by the group he could be healed by techniques of interpersonal interaction, but if he had bad genes, effective treatment was far in the future.”18
And then there are treatment cycles. In the 1880s and 1890s, a great cycle began, as the patent-medicine industry flooded the world with drugs of dubious safety and utility. Still, people were just accustoming themselves to the idea that the highway to good health lay in pharmaceuticals, and these products were enormously profitable. But industry’s invasion of medicine, so evident around 1900, subsided. George Simmons, who was instrumental in creating the AMA Council on Pharmacy and Chemistry in 1905, wrote, “Since the Council began its work . . . there seemed to be no statement too silly, no claim too extravagant, and no falsehood too brazen for use by those who wrote the advertising literature that physicians were asked to read and to believe.” He lamented above all, industry’s corruption of the journals and textbooks: “This commercialized materia medica has blighted our literature by debauching our medical journals and even by tainting our textbooks.”19
To be sure, the age of patent pharmaceuticals did not sweep all before it. For the next 40 years, drugs that physicians prescribed (called “ethical specialties”), having at least some evidence of safety and efficacy, were the order of the day. Almost none of the drugs of that era were hugely effective, with the few exceptions being insulin, the opiates, and the barbiturates.
Nonetheless, this cycle had ushered in a time of almost frenetic treatment. In 1909, William Osler, professor of medicine at Johns Hopkins University, cautioned colleagues that, “The literature that comes to us daily indicates a thralldom not less dangerous than the polypharmacy from which we are escaping. [Osler believed the fewer drugs, the better.] I allude to the specious and seductive pamphlets and reports sent out by the pharmaceutical houses, large and small.” He absolved Parke-Davis in the United States and Burroughs Wellcome in
England as “pioneers in the science of pharmacology.” But the rest “traded on the credulity of the profession, to the great detriment of the public.”20
By 1929, the Council, as Paul Nicholas Leech of Chicago said, had “more than 100,000 index cards dealing with drugs and drug therapy” in its files.21 One observer, commenting in 1929 on this profusion, said, in a statement entirely applicable to our own times, “The almost daily announcement of new discoveries has produced a national state of mind in which we are surprised at nothing and, too frequently, are willing to accept at face value anything presented with the merest semblance of truth.”22 But pharmaceutical science was ending this credulity. In that file box with its 100,000 index cards lay the death knell of the cycle: the age of patent psychopharmaceuticals ended.
So, we should not imagine that industry’s invasion of the practice of medicine is a recent phenomenon. At an AMA symposium on drug therapy in 1929, “emphasis was given to the need to replace the detail man [drug rep] as the main source of instruction in the use of medicines.”23 This cycle ended with the AMA’s cold-eyed assessment of patent remedies, discarding most of them. As mentioned, in 1905 the AMA’s Council of Pharmacy and Chemistry was founded, and it systematically evaluated new compounds. Simultaneously, Arthur Cramp became director of the AMA’s Bureau of Investigation from 1906 to 1936 (it was originally called the Propaganda Department); his three-volume Nostrums and Quackery and Pseudo-Medicine, published between 1911 and 1936, makes riveting reading for students of the history of gullibility.24 In the section on “female weakness,” we learn that Lydia E. Pinkham’s Vegetable Compound, a marketbeater around the time of the First World War, was the remedy of choice for “tired nervous mothers.”25
Thus ended the cycle. This is not to deny that effective agents for mental disease were not introduced: they included niacin for cerebral pellagra, penicillin for neurosyphilis, chloral hydrate for sedation—but they were few and far between and in no way gave rise to a specific science of treating diseases of the brain and mind.
The second cycle, the Age of Psychopharmacology, began around 1954, with the introduction of the antipsychotic chlorpromazine (Thorazine). For the first time, truly effective drugs became available for the treatment of serious mental illness.
However, a hallmark of the second great cycle was the invasion of psychiatry by industry. Yet, as stated, it would not be correct to think of this as a new problem. Around 1900, observers called attention to physicians who endorsed products for money. In 1907, Simmons said, “An honest, conservative statement about the merits of a proprietary preparation is as rare as are sweet violets in Ireland.”26 So again, the tendency of clinicians to sign off on products for pay is not new—but in those earlier days the purveyors typically did not have academic
appointments nor were they regarded as leaders! The point is that the invasion of psychiatry by industry that bedevils us today is not recent—merely extraordinary in that it is physicians at the top of the heap, rather than those at the bottom, who are the perpetrators.
Thus, after 100 years, unscrupulous manufacturers would once again etiolate the evidence base of medicine, and as a result, our own days have seen the end of the Age of Psychopharmacology, the completion of this most recent great cycle. This time, there was no guardian at the ports; the FDA proved incapable of preventing the jury-rigging of the evidence of drug safety and efficacy, and, it would be fair to say, the pharmaceutical industry invaded and took possession of the practice of clinical psychiatry.
Thus, this book is about the rise and fall of the second great cycle, the Age of Psychopharmacology. The fall? Psychiatric drugs are still prescribed today in massive numbers. Yet the frame is shifting. Observers increasingly recognize that the intellectual paradigm of “neurotransmitters and their reuptake” has been exhausted, that there are no new drugs in the pipeline, and indeed that no new drug classes or novel mechanisms have been conceived for decades. The field’s professional literature, at least that regarding drug trials, has been hopelessly corrupted, and the prescribing of an endless chain of SSRIs (Prozac cousins) is something you don’t actually need specialty training in psychiatry to do. Nor, for that matter, as the psychologists increasingly clamor, do you need a medical degree to do it.
So, the next big thing will soon come along. We cannot yet know what it will be, but the second-generation antipsychotics that now clutter the treatment of depression are increasingly recognized as grossly inappropriate, and the prescribing of these powerful drugs for children is seen as a form of child abuse. The SSRI “antidepressants,” as they are cleverly termed, are now viewed as drugs that suppress emotion rather than relieving depression. Their metabolites currently pollute our lakes and streams—and soon the Green New Deal will cry “Enough!”
Teasing Society from Biology
We live in a society where the belief is encouraged that one of four people in your subway car has a mental illness. A government survey for 2008 to 2012 found that “Among adults aged 18 or older, an estimated 22.5% (51.2 million adults) had in the past year at least one of the diagnoses [that interviewers assessed]; that is, almost a quarter of adults in the United States had one or more mental disorders (including adjustment disorder and substance use disorders) in the past year.”27 A quarter of the population do not have diseased brains. This extraordinary figure is possible only with the aid of culture.
Mind versus brain is often presented as a dichotomy. In figuring out why people become ill, you have to choose one or the other. But the two positions can exist side by side, depending on what illnesses one is discussing.
By the 1970s, there was a consensus outside of psychoanalysis that a “medical” psychiatry existed in which the major illnesses—melancholic depression, catatonia, and schizophrenia—were brain diseases that responded to the new drugs and to ECT (electroconvulsive therapy). The psychoneurotic disorders, by contrast, were considered psychogenic illnesses that responded to antineurotic medications, or nerve pills, such as meprobamate in the 1950s or the benzodiazepines in the 1960s and 1970s. In the 1990s and the new century, the SSRIs attempted to fill this role, but with little efficacy. Psychiatry thus followed the “medical model,” in the sense that the major disease entities were considered to be brain diseases that could be individuated following the tenets of the medical model: (1) identification of a disease entity on the basis of specific signs and symptoms; (2) verification of the entity on the basis of biological tests; (3) validation of the entity on the basis of response to treatment. By the 1970s, there were two diseases that had been thus identified: melancholic depression and catatonia. Schizophrenia as a distinctive disease entity—an improbable assemblage of various disease conditions—was beginning to deconstruct itself. British psychiatrists Ida Macalpine and Richard Hunter epitomized this “brain” perspective in the Times Literary Supplement in 1974: “The abnormal mental state,” they said, “is not the disease, not its essence or determinant, but an epiphenomenon. This is why psychological theories and therapies, which held out such promise at the turn of the century . . . have added so little to understanding and treatment of mental illness. . . . Type and degree of mental disturbance are determined by type and seat of brain disturbance.”28 This is a provocative statement of a highly reductionist position: mind disease reduces to brain disease. It would have sat well at the neurological National Hospital in Queen Square in London, where Hunter was physician in psychological medicine.
By contrast we find Mickey Nardo, practicing psychiatry in a charity clinic in the backwoods of Georgia, who emphasized disorder of the mind rather than brain disease. To be sure, he said, there were show-stopping illnesses, such as melancholia and schizophrenia. “In the 1970s, there was something of a growing consensus that Melancholic Depression and the Depressions associated with Manic Depressive Illness were prime candidates for biological research. The genetics were right. The clinical syndrome was unique. There were promising biomarkers: DST [the dexamethasone suppression test] and REM latency [rapid eye movement latency].” So that was the biological side.
But then, continued Nardo, there was another side. “When I see patients in the clinic tomorrow, I’m not likely thinking that many of them have brain diseases. The colossal failure of the research enterprise to find anything may be that
there’s not anything to find.”29 On another occasion, he said, “I worked in two clinics yesterday and I saw only one patient [who] might fit such a [biological] model—a sixteen-year-old with attention deficit disorder with hyperactivity (diagnosable from 100 yards). Everyone else had the kind of confusing complex of problems that afflict real people—no [diagnostic] entities noted. Some got medicines. Some got taken off medicines. Some were helped. Some weren’t.” Nardo then turned upon psychiatrists who insisted on reducing everything to specific diseases, “determined to make psychiatry ‘evidence-based’—more like the rest of medicine with distinct disease categories, structured interviews, and treatment protocols. The focus was on treatments rather than on broad-based attempts to understand the breadth of the problems—more on neurochemistry than people.”30 Here was a seat-of-the-pants articulation of the difference between brain diseases, such as melancholia with the dexamethasone suppression test for it, and the riot of stress, distress, and unhappiness that Nardo saw on a daily basis in the charity patients. This is a differentiation that brain biologists like Richard Hunter missed.
Clearly, not all psychiatric disorders are brain diseases. Yet some are. The failure of the psychopharmacological paradigm lay in expanding the biological sort to encompass virtually the entire field. This expansion was accomplished by declaring that basically everything was treatable with drugs. It wasn’t a random observation, born of an idle Tuesday afternoon seminar. The relentless expansion of indications was essential in the cut-throat commercial competition between companies: expanding indications meant expanding sales. This was commerce, not science.
How to find a golden mean between the biological and the social? Joseph Zubin, who founded the biometrics research program at the New York State Psychiatric Institute in 1954 and ended as professor of psychiatry in Pittsburgh, said at the 1988 meeting of the American Psychopathological Association, “The biological variables we talk about have primarily been wired in through evolution. The psychosocial variables came much later, when culture took over. Cultural transmission is not as efficacious, not as direct, and not as built-in as the biological, and yet it represents a very basic underpinning of total behavior.”31 Here, biology and culture are clearly juxtaposed, although it would be difficult to sort these out in dealing with patients.
Psychopharmacology and its diagnoses swam even further out of view in the mid-1950s when Frank Berger, a Czech-born psychiatrist, introduced meprobamate (Miltown), the first blockbuster drug in psychiatry. So, you’d think Berger would have bought into the biological model of specific medications for specific diseases? Not at all. This is what he told Leo Hollister (who was the éminence grise of US psychopharmacology) in an interview in 1995 about his arrival in the United States just after the war. Berger’s first job was at a psychiatric clinic of the
University of Louisville: “My feeling was that most people we saw had really no psychiatric disorders. They were people, in my opinion, with problems of living, people who did not get along with their spouses, did not get along with their children, did not get along with their boss, and had not been taught, had not been educated, had not been prepared to handle all the crises of life. So they got stressed, broke down, and had to see a doctor, and the doctor did not know what to do. So he put one of the psychiatric names on them.”
Hollister: “That’s right. You are absolutely right!”32
