- Good evening and welcome to the Marian Miner Cook Athenaeum. My name is Henrietta Toivanen and I'm one of the Ath fellows this year. The question of mental health is extremely relevant in the context of college life. Given the prevalence of different psychological conditions among us, the lack of help that many of us feel, and the negative longterm consequences that untreated illnesses lead to. Given that 75% of mental health conditions emerge before the age of 24, adolescence is a critical time for finding successful interventions and effective care. Unfortunately, as we will hear tonight, there's a vital need for identifying better approaches to the treatment of mental illness and enhancing the overall psychological well-being throughout our lives. Our speaker tonight, Robert Whitaker, is an award-winning journalist who's career has focused on the burden of mental illness in society and whether the cure, psychotropic drugs, might actually contribute to their cause. He's the author of five books, and has received recognition from the Discover magazine and received the Investigative Reporter's and Editor's Book Award in 2010. He's also the founder of madinamerica.com, a website that features research, news, and blogs from an international group of writers interested in rethinking psychiatry. As always, I must remind you that audio and visual recording is strictly prohibited. Please join me in welcoming Mr. Whitaker to the Athenaeum. (audience applauds) - So first I wanna say it's a real pleasure and an honor to be here. When I got this invitation, the first thing I did is I went to the website and looked at the roster of speakers who have been here, and it's really incredible, this speaker initiative at CMC is just unique and absolutely astonishing, so it's a real honor to be here. So now my first question I have to ask, how many people came for the dinner? (audience laughs) You can raise your hand. There's a brave man. (audience laughs) I wouldn't blame you frankly, I think I'd be here every night. So here's what I wanna do in the next 45 minutes. I really want as much as anything is raise a question for you all. I think it's an important question. And that is, the problem of mental illness or discussion about mental illness has become ever more prevalent in our society. We have a narrative around what's going on and best treatments. And my real question to raise right now is is our current paradigm of care working for us as a society? Is it working for individuals, et cetera? And is it based in a narrative that if you dig into the science you find that it is a scientific paradigm of care? Or is there a counternarrative out there to be discovered that perhaps could lead us to a different form of care or a different paradigm of care that would hold open the hope of producing much better outcomes? So that's the question I want to present to you all here tonight, and really was the question that I raised and investigated in this book Anatomy of An Epidemic, which was first published in 2010. Now I was saying to myself that maybe I should title this talk, not Anatomy of An Epidemic, but How I Became a Heretic. Because in essence, you have invited someone who ended up with a view of heresy so to speak in terms of relationship to a common narrative. And here's how my own path came to this story. So I was a medical journalist for a long time. I worked as the director of publications at Harvard Medical School, in the early 90s when there was a lot of talk about evidence-based medicine. I then co-founded a publishing company that looked at the business of developing of new drugs and I had absolutely a conventional understanding of psychiatry. And then in 1998 I co-wrote a series for The Boston Globe that was really just focused on abuses of psychiatric patients in research settings. And the context for that series was, among other things, is that we're making great progress in understanding the biology of mental disorders. These drugs fix chemical imbalances in the brain and one of the abuses of patients that we focused on were studies funded by the NIMH, where they had withdrawn antipsychotics from schizophrenia patients, and we said that's abusive. These drugs are like insulin for diabetes. You would never withdraw insulin from a diabetic to see if they became sick again. So this is an example of a government-funded study that was abusive and unethical. And we had some other things we looked about sort of abuses of patients in psychiatric research settings and I was rewarded for that series. It was a finalist for the Pulitzer Prize, it won the George Polk Award. So although it was pointing out problems within psychiatry, the frame of reference was within a conventional narrative that we're making progress and we have these new drugs that are so great, et cetera. But then at the end of that series, after it got published, I came upon two studies that really made me question what I had just written about. One were studies done by The World Health Organization, which had twice compared outcomes for schizophrenia patients in three developing countries, India, Colombia, and Nigeria, with outcomes for people diagnosed with schizophrenia in the US and five other developed or rich countries. The first study was five years long and they were surprised or stunned, the investigators, to find that it seemed that outcomes were much better in the poor countries. Now why would that be? And so they said what's going on here? And they hypothesized after the first such study, maybe the reason for the better outcomes in the poor countries is that the patients were more medication compliant in India, Nigeria, and Colombia, which is a valid hypothesis. If medications are thought to be so essential to longterm outcomes, longterm care, then more compliance should lead to better outcomes. So they looked at compliance in this second study and here's what they found, is that the medications were being used differently in the poor countries, they were being used acutely, but not chronically. So in the poor countries only 16% of patients were regularly maintained on the drugs and of course that is the standard of care in the US and other developed countries. And here was the phrase that made me wanna write a book, the World Health Organization concluded that living in a developed country is quote a strong predictor that you won't have a good outcome if you're diagnosed with schizophrenia. And I wanted to know why was living in a developed country a predictor of a poor outcome. Now there was one other study that really belied what I knew to be true. This was a study done by Harvard researchers in which they looked at outcomes from schizophrenia patients longer term outcomes over the past hundred years, and what they found is, what they reported in 1994 is that schizophrenia outcomes had actually declined in the United States in the last 15 years and were now no better than they had been in the first 30 years of the 20th century, from 1900 to 1930. So all of a sudden I had one belief in a conventional narrative, and now I had research that made me question that conventional narrative. So what we're gonna do in the next 35 minutes is look at the conventional narrative, and then in a very rushed way to see if as we move through history and science if it's really supported or is there history and science actually telling us a different story, okay? So what's the conventional narrative that really governs our care? It goes like this: In 1955 a drug called chlorpromazine, which you also remember as Thorazine arrives in asylum medicine. And this drug kicks off a psychopharmacological revolution and a leap forward in care. Chlorpromazine is remembered today as the first antipsychotic. You hear that word antipsychotic? As if it's an antidote to psychosis. And then we get antidepressants and we get antianxiety agents. So instead of just having tranquilizers or sedatives to treat people with mental disorders, now we have agents that are antidotes to some sort of pathology is the idea, okay? That happens in the 50s and 60s. The benzodiazepines in particular become very popular. Then the next step is 1980, the American Psychiatric Association publishes the third edition of its Diagnostic and Statistical Manual, and with this manual it reconceptualizes mental disorders. So if you go to DSM 1 and DSM 2, there's a lot of freudian ideas in the diagnostic constructs, there's a lot of psychological problems that lead to distress, but with DSM 3, the American Psychiatric Association says we're going to conceive of disorders as brain diseases, diseases of the brain. And this was actually a big change, to see disorders as generally diseases of the brain, and we're also gonna get a lot of new constructs at this time, for example, ADHD is a diagnosis made for the first time. It's also DSM 3 now, that is going to launch an increase in diagnosis, an increase in psychiatric drugs, and diagnosis across the lifespan. We're gonna start diagnosing children all the way to elderly. I'm so old that when I was growing up in high school, I didn't know anybody diagnosed with a mental disorder. And when I was in college, we just didn't have that discussion. Going forward, this was seen by the way as an advance as well, this new conception, adopting a medical model. Jeffrey Lieberman, the former president of the American Psychiatric Association recently wrote a book about this and he says this: DSM 3 is the most important book written in the United States in the last 50 years. Not book of psychiatry, any book. And I agree, it is the most profound book, important book in terms of its effect on society, written in the last 50 years. 'Cuz it's gonna give us a new philosophy of being. It's going to dramatically expand who gets diagnosed, and it's gonna dramatically expand the use of psychiatric medications. And as an example on this, in 1980 there were 30 million prescriptions filled for antidepressants in the United States, and now we fill about 270 million prescriptions for antidepressants. Now if you go forward with this story of progress, it goes like this: Prozac arrives in 1987, this is the first of the second generation of psychiatric drugs, which are said to be safer and more effective than the first. We get the SSRIs, then we get the atypical antipsychotics, this keeps up this ladder of progress, and then we hear with great regularity that these drugs are fixing chemical imbalances in the brain. That depression is due to low serotonin, you take an SSRI, it ups serotonergic activity and there you get the like insulin for diabetes metaphor. Antipsychotics the idea was that a psychosis, schizophrenia was due to too much dopamine. These drugs by blocking dopamine are helping to bring it back into balance. Now think of that metaphor. That metaphor is telling you of an extraordinary medical advance. It's telling us that we have identified the molecule that is amiss in depression, complicated thing, or we have identified the molecule that is amiss in psychosis schizophrenia. That's a story of ... And not only have we identified the pathology, we have an antidote to that pathology, and if you look in the history of medicine, that is a model for great advances in care. You identify the pathology, and you develop an antidote to that. And in 1998, US Surgeon General David Satcher wrote like a 400, 500 page report on mental health and he says this: Prior to 1955 we lacked treatments that would prevent people from becoming chronically ill. Now we have a vast array of safe and effective treatments for treating well-defined psychiatric disorders. And that's that conventional narrative, the story of progress. So what I did in Anatomy of An Epidemic, in order to begin to put that narrative under a microscope to see if it's true, that we really have made all this progress, was just look at the number of people on government disability due to mental illness, and how has it changed as this psychopharmacological revolution unfolded? Because generally, when you get a medical advance, when you have a revolution in care, you're gonna see the burden of that illness diminish in society right? That's what you expect. Well if you look at just a number of people who can't take care of themselves, if you go back to 1955, there were about 350,000 people in state and county mental hospitals with a psychiatric diagnosis. There was another 200,000 people with basically Alzheimers, that sort of thing. 350,000 people with psychiatric diagnosis, that's a disability rate of about 1 in 500 people at the time. Now we deinstitutionalize and we set up a different system for taking care of people who are disabled by mental illness they can receive an SSI or an SSDI payment. And what other researchers have said, if you wanna track the number of disabled mentally ill in our society, you have to look now at the number of people on SSI or SSDI who were declared eligible for that program due to mental illness. And you go to 1987 and there's about 1.25 million adults on disability due to mental illness, the year that Prozac arrives. So it went from 330,000 to 1.2. There's an obvious caveat right? Maybe you had to be a lot sicker to be in the hospital in 1955, to be on disability in 1987, so maybe it's an apples to oranges comparison. 1987 forward, we have the same metric. And so where are we at today? We're closing in on five million people on disability due to mental illness. So during this time of the second generation drugs, where we've had this explosion of diagnosis and this explosion of use of drugs, rather than see the burden of mental illness decrease in our society, at least by this one measurement, we're seeing it increase. Now I should say two other things: In 1987 there were 16,200 children who were receiving an SSI payment because of a mental illness. We now have about 700,000 children receiving a payment because of mental illness. And if you look at the children who receive it, when they go to age 18 about two thirds go onto adult disability. Finally, you're seeing this rising burden of disability in country after country that has adopted this paradigm of care. You see it in the UK, you see it in the Scandinavian countries, you see it in Australia, Canada, New Zealand, et cetera. Now that data doesn't prove anything does it? It doesn't prove that there's a problem necessarily with the paradigm of care, but it at least raises a question of what's going on. And by the way, in 1987 we as a country spent about 800 million dollars on psychiatric medications. Now we're spending about 40 billion dollars a year, so it's like a fifty-fold increase in spending. So you have a question at least I think, a reason to question the conventional narrative right? So what I did in Anatomy of An Epidemic is I asked a new question. I said we have studies when we get psychiatric drugs that when they come to markets you test them against placebo and as long as they beat placebo by some amount over the short term they're declared effective and they're approved for market, right? What I asked in this book was a new question. How are these medications shaping people's lives over the longterm? One year, two years, five years, 10 years, 20 years? Which is a very different question. And I think one of the reasons I've been on the road basically since this book came out is because it is a new question that obviously has some reason to investigate. So now real quickly, lets put the conventional narrative under the microscope and dig into the scientific and literature and see what we find in two ways. Do these drugs in fact fix chemical imbalances in the brain, and how do these drugs maybe change the brain? And then we'll do a quick case study of the longterm effects of antipsychotics, and we'll see if we can do that in 30 minutes, alright? So if you look at the chemical imbalance theory of mental disorders, and the last study I saw said about 80% of Americans now know that depression is caused by low serotonin, so this is a popular understanding. You find that it came about from an understanding of how drugs act on the brain and not from an understanding of what was going on in the brains of people so diagnosed. So for example, just to simplify the story just a bit, how does an SSRI work? How does a selective serotonin reuptake inhibitor work? Well neurons communicate in the brain in this way, you have a presynaptic neuron, I'm sure you all know this, it releases that molecule into that tiny gap between neurons which we call the synaptic cleft. That molecule, whether it be serotonin, dopamine, it binds with receptors on the receiving neuron which we call the postsynaptic neuron and we say it fits like a key into a lock, right? That's how messages are passed. And then the brain has to have a way to end that signal, so that serotonin or that dopamine has to be removed from that synaptic cleft. It's removed in one of two ways, it either is taken up into the presynaptic neuron via reuptake channels or an enzyme comes along, metabolizes the serotonin, carts it off as waste. So, an antidepressant blocks that reuptake process, the serotonin stays longer than normal in the synaptic cleft, it's upping serotonergic activity, so researchers hypothesize well maybe people with depression therefore have low serotonin. In other words the hypothesis was born of understanding how the drug worked. And the other part of the chemical imbalance theory came from an understanding of how antipsychotics worked. What do they do? They bind with the receptors on the postsynaptic neurons but it's like pouring glue into those locks, they don't activate the receptors, they block it, therefore they depress dopaminergic activity, they act as a brake right? So researchers hypothesize well maybe schizophrenia or psychosis therefore is due to too much dopamine activity alright? That was how the hypothesis was formed. Just because the serotonin theory is better known we'll follow that. They began looking in the late 70s, early 80s, well do people with depression, prior to going on an antidepressant, do they have low serotonin? Do they find it? And as early as 1984, the researchers from the NIMH said we're not finding it. I'll just quote: "Elevations or decrements in the functioning of serotonergic systems per se are not likely to be associated with depression." This was the first round of studies. Prozac comes onto market in 1987 and there's a new round of studies throughout the 1990s and here's the results of these studies. This is Stephen Stahl, he writes a textbook called Essential Psychopharmacology in 2000. "There is no clear and convincing evidence that monoamine deficiency," serotonin is a monoamine, "accounts for depression, that is, there is no real monoamine deficit." If you go with the dopamine theory of schizophrenia it's a bit more complicated. There's still some people looking at whether there's subsets of people with sort of abnormal dopaminergic activity. But as a general hypothesis that as a matter of course people with schizophrenia had too much dopamine activity, that fell apart in the 1990s and here's a quote from Steven Hyman, he's the former director of the NIMH, he's a neuroscientist at Harvard, he wrote a book called Molecular Psychiatry, he says this: "There is no compelling evidence that a lesion in the dopamine system is a primary cause of schizophrenia, we didn't find this." Then you have someone, Kenneth Kendler, coeditor and chief of Psychological Medicine, he was one of the researchers that really investigated this chemical imbalance theory of mental disorders and he writes in 2005, he summarized this long history, "We have hunted for big simple neurochemical explanations for psychiatric disorders and we have not found them." And here's my favorite quote. In truth the chemical imbalance theory has fallen so apart within mainstream psychiatric research that you'll see psychiatric researchers really saying that was an invention of the drug companies and here you'll see this. Ronald Pies, who's a former Editor in Chief of Psychiatric Times he says this: "In truth, the chemical imbalance notion was always a kind of urban legend, never a theory seriously propounded by well-informed psychiatrists." So what you see when you investigate the chemical imbalance theory, which is that part of that conventional narrative that science didn't find these sort of specific molecules that were the cause of mental disorders, okay? That's one part. There's a second part to the chemical imbalance story that is not often talked about. What they also found however, is that the drugs in essence induced the very problem that was hypothesized to cause the disorder in the first place, and I'll explain this. You go on an antidepressant, it acts as an accelerator serotonin right? Now your brain having all these feedback mechanisms, it now tries to compensate, to adapt to the presence of the drug, and what does it do? Because the drug is acting as an accelerator it will put the brake on serotonergic activity. It does it in two ways. The presynaptic neurons will put out less serotonin for a time and then the receiving neurons, the postsynaptic neurons will down regulate or decrease their density of serotonergic receptors. And researchers say the brain is trying to maintain a homeostatic equilibrium. But there is an irony here, and as we go through the literature longterm we're gonna see this worry crop up. Depression for example, was hypothesized to be due to too little serotonin. They found that prior to going on the drug they did not find this deficit, but that after you're on the drug physiologically it drives your brain into a subsensitive state, okay? And it's called developing oppositional tolerance. Now let me make a comment here before we go on. When I give talks or when I wrote this book, it's not medical advice for anybody. It's just information that I hope can inform a societal discussion perhaps about what we might do better. So if anybody here is taking medications, you should never think about this as medical advice for you individually okay? So this is just a part of societal discussion. So real quickly, lets now go through the longterm outcomes literature for antipsychotics going back really through what history and science can tell us. Now I told you that I'm a reporter, so the first thing I wanna do is find the evidence base for the use of antipsychotics because clearly there's going to be an evidence base. Well the short term I just told you, what is it? Going back to the 50s and 60s, people came into an emergency room, they were put on antipsychotics, they were randomized, half put on drug, half put on placebo, and after a certain period of time, four weeks, six weeks, the people put on drug were doing better. They had a greater diminishment of their psychotic symptoms. That's evidence of short term efficacy right? Now you're a doctor 1958, 60, 62, what's your next question? You're using these drugs, how long should I keep my people on these new drugs? So with that question in mind they ran studies designed like this, they took that percentage of people that were good responders to antipsychotics, 'cuz they had to be stable, and they ran studies where they withdrew the drug from half the people. They maintained the other half on the drug and with great regularity the people withdrawn from the drug abruptly usually relapsed at a higher rate. Meaning that their psychotic symptoms came back, right? So what did doctors see? Aha, you go off the drug and the disease returns. And that becomes your evidence base for longterm use of the drugs, okay? It's these relapse studies. And one other part of the evidence base, if you're a doctor what do you see? What does your clinical experience tell you? Person comes in, you give them a drug, it works, right? Then the person goes home says I hate these drugs, it makes me feel sort of sedated or whatever, I throw 'em away and I relapse, come back to your emergency room. You see that the person needs to be on the drug. That's what you see. Was there a limitation or is there something missing from the relapse studies in terms of an evidence base for longterm use? And pretty quickly you can see this, when you get that high rate of relapse following drug withdrawal, is that a withdrawal effect? 'Cuz your brain has changed. Or is it the return of the disease? And you may be mistaking a withdrawal effect for this high degree of relapse. That's number one. Number two, the relapse literature doesn't tell you about how people are functioning longterm. Are you working, are you socializing? That sort of thing. What it's telling you is if you're on medication, you come off abruptly, you're likely to do really poorly, but it doesn't tell you how you're changing people's lives over the longterm. So again, I'm a reporter doing that. So I can see the recognized flaws in the relapse literature which is what is cited for longterm use. So now I wanna know are there other studies that people can point to that show that antipsychotics improve the longterm course of schizophrenia. And when you do that you suddenly come upon a very surprising finding in the literature. They will say we don't have that evidence. So for example, Emmanuel Stip in 2002, he's a psychiatrist at the University of Montreal, he writes a paper, he says "After 50 years of neuroleptics," that's another name for antipsychotics, "are we able to answer the following simple question: are neuroleptics effective in treating schizophrenia? There is no compelling evidence on the matter when longterm is considered." So for me this is like a green light, right? Someone has tried to find this evidence and is saying we don't have it. And then he says this: "If we wish to base psychiatry on evidence-based medicine, we run a genuine risk in taking a close look at what has long been considered fact." And I love this line, first of all it made feel that okay, now I can go into the literature without being seen as having an ideological drive, because he's saying this is a valid inquiry to take a closer look. And in essence, by you all inviting me here tonight, you're taking this risk at taking a closer look, okay? 'Cuz it might be surprising. So what do we find out if we start to go through the literature and try to see how medications or in fact antipsychotics, the very drugs we should be sure are improving the longterm course, what do we find? Well the first thing you wanna do if trying to figure out about a longterm course, you have to figure out what's the natural recovery rate, right? What do you do in the absence of an intervention? And you know the Hippocratic Oath, don't make your patients worse? It's often interpreted meaning don't make your patients worse, don't make them worse than when they came in to you. But actually, I think what Hippocrates was getting at is a much more subtle thing. It was this: there's often a natural capacity to recover in nature, and in order for your intervention to not make patients worse on the whole, it has to beat that natural capacity to recover. So one of the first things you wanna try to flesh out is what sort of outcomes were we getting for schizophrenia patients when the drugs were introduced? Now our memory is people never got out of the hospitals right? They remained chronically ill, that's part of the narrative is we got these drugs that made it possible to deinstitutionalize. There was a meeting in 1956 by the Psychopharmacology Service Committee at the NIMH and they took up this very question: What sort of outcomes are we getting today with first episode schizophrenia patients? And here's what they found, they looked in the past 10 years, about 65%, 70% would be discharged in 12 to 18 months and in five year studies about two thirds were living outside the hospital and employment rates were above 50%. And they actually came up with this sort of spectrum of outcomes at this time: one third will recover, they'll have a time of schizophrenia and then it will dissipate. There will be another third that might have sort of ongoing symptoms of some sort, but they can function outside the hospital, and then one third remain in the hospital. But why do we remember the disorder as chronic for everyone? Well if you're a psychiatrist working in a hospital, who ends up in the hospital year after year? It's the chronic patients, right? 100 come in, 70 leave, you're left with the 30, and that's who you're gonna see year after year. Okay, but that's the baseline, it's not quite the chronic outcome we think. Real quickly, next the first longterm study is done in 1963 by the NIMH. It has four arms: three drug arms, three groups are randomized to an antipsychotic, the fourth to placebo. At the end of six weeks the drug-treated groups are doing better. In fact, this study is still cited as proving the efficacy, it's also this study that changes the names of these drugs. Before the study they were known as major tranquilizers, after this study they're called antipsychotics or antischizophrenia drugs. But if you look at the data, many of the placebo patients in fact were getting better as well, just not as much, then they're discharged and at the end of one year the researchers found something odd. Those randomized to drug had higher relapse rates at the end of one year than those randomized to placebo. So at this very early moment of the research literature you see the vaguest tint of a paradox. Could drugs that are effective over the short term, could they for some reason be increasing the chronicity over the longterm? Your next data point is what did physicians at the time say about the course of schizophrenia patients now that they had this new drug, and you'll hear this: Boy my patients are getting better faster, but boy they're coming back to the hospital in droves. And they even invent a phrase called the revolving door syndrome. The next thing you hear from clinicians, that does show up in NIMH records, they said we've got another problem, it seems that when people have relapses on drug, the relapse is more severe than we used to see on placebo. So there was clinician worry. And result of this in 1970s the NIMH conducts four studies to revisit the question of the longterm use of antipsychotics. One's a retrospective study done by Samuel Bockoven in Massachusetts, he has outcome data for a group of patients in '47 treated with psychosocial care, but no drugs, a similar group of patients in '67 treated with psychosocial care plus drug, and here's what he found: a little higher relapse rate in the modern group, but much more social dependency, less employment in the modern group and he says if we're interested in longterm functional outcomes, we may need to rethink this. Then there were three studies, two of them were done here in California, one by the head of the schizophrenia studies at the time where they took newly diagnosed patients, they were either randomized into conventional care or experimental care where they would get some sort of milieu care, and the medication use would either be no medication use or selective medication use. No immediate use but then if people weren't getting well they would put them on the medication. So it was a selective use model. In each case, and there was one done at a hospital by the NIMH, in each case the selective use model had better overall outcomes, both functionally and in terms of relapse rates. That was one finding. The second finding was there would be a certain percentage of patients treated without drugs for a first episode that could get through that episode without going on the drugs and it would be that never exposed group that would tend to have a good outcome at two years and three years. And then a man named William Carpenter, who's still a famous name in schizophrenia, raises the critical question. And it's a really profound question, he says this: We know that once you're placed on medication you're less vulnerable to relapse if you stay on the drug than if you withdraw. That's the relapse studies. But now he's got these other studies where you're seeing higher relapse rates in the drug-exposed patients. He says: But we have to raise a question, what if these patients had never been exposed to drugs in the first place? Maybe the drugs cause a biological change, a change in the brain, that makes people more biologically vulnerable to psychosis than they would be otherwise in the normal course of the illness. So this is a brilliant moment for science in my opinion. What they're saying is science perhaps has illuminated a problem that's not visible to the clinician, okay? And then we get people from McGill University who put together a biological explanation to explain this paradox. They said this: Antipsychotics block dopamine receptors, they act as a brake. What does your brain do in response? It puts down the accelerator on dopamine activity, it does this in two ways, the presynaptic neurons put out more dopamine than normal, the receptors on the postsynaptic neurons an up regulator increase their density receptors, the brain is now they said super sensitive to dopamine and that has two consequences. One, when you come off you're gonna have severe relapses, but even if you stay on you may get chronic psychosis and here's what they wrote: "Neuroleptics can produce a dopamine supersensitivity that leads to both dyskinetic and psychotic symptoms. An implication is that the tendency towards psychotic relapse in a patient who has developed such a supersensitivity is determined by more than just the normal course of the illness." And here's why this is so profound, you're not talking about an adverse effect, you're talking about a worry that on the benefit side of the equation, on the whole, antipsychotics actually increase the chronicity and the biological susceptibility to psychosis. That's the worry, it arises in 1980, they do a test of their patients and they said 30% of their patients that had been on drugs longterm now had chronic psychosis okay? It rises. Now imagine I'm Guy Chouinard, he's one of the two investigators, you're a bunch of psychiatrists, it's 1982, and I'm Guy Chouinard and I say: Listen, we've got a problem, we have these drugs that work over short term, they're the centerpiece of our care, but I think they're making people more psychotic over the longterm because of this biological change. What do you do in the audience? You can't believe it. Cognitive dissonance takes hold and there are stories about people standing up and going are you telling me the very drugs I use to treat psychosis could be making people worse, more psychotic? And this gets pushed aside. So that's the early 1980s. So now the question is, was it a false worry or is this worry still present? Is it coming back? Well I mentioned the WHO studies, remember, that you saw better outcomes in the poor countries. We have a new study in which in the new study for three years, everybody in the study is maintained on medications for three years, including in the poor countries. And now the outcomes in the poor countries are in fact worse than in the rich countries. But it's not that our outcomes have improved, their outcomes have deteriorated. That's one data point. Second, this is really I think a little upsetting, but now we get MRI technology. There's been a lot of studies showing brain volume changes related to the drugs over time. Some of this research came from Nancy Andreasen, who's the Editor in Chief of The American Journal of Psychiatry. This is mainstream. And she found that over time you see a brain shrinkage, a decrease in brain volume, it's basically dosage-related. And then she also found as this happens over a course of five years, you get an increase in negative symptoms, an increase in functional impairment, and an increase in cognitive decline. So you have a model you say you have an agent that comes into the brain, shrinks brain volumes, and as that happens you get this deterioration in symptoms. And then we have a study, the best long running study of outcomes of psychotic patients, it's done by Martin Harrow at the University of Illinois. Beginning in the early 1970s, early 1980s, he began following 200 psychotic patients, 64 with schizophrenia and the others with milder psychotic disorders, and it's a naturalistic study. People come into the hospital, they're treated with medication, they're discharged, and now he's just gonna follow them at two, four and a half, seven and a half, 10, 15, and 20 years. His hypothesis is that those who take themselves off medication will have horrible outcomes. We're gonna see them in jail, we're gonna see them homeless, we're gonna see them chronically psychotic. That is the expectation. Now, one of the things that is really good about this study, at the end of 15 years of the 200 that he recruited in the study, 145 were still in the study. And anybody who's done research on schizophrenia patients, that is a really low loss to study, that's 77% retention rate. At the end of two years, if you look at his data, say the number of people in recovery, and he defined recovery as asymptomatic and you had to be working or in school halftime, there's very little difference between the people off medication and those ... Of the 64 schizophrenia patients, 25 stopped taking their antipsychotics by year two. There's basically no difference in outcomes at year two. But between year two and four and a half, their outcomes diverged notably, such that by the end of four and a half years 40% of those off medication or in recovery versus 5% of those on medication. And you can look now at any domain: cognitive function, anxiety levels, psychosis levels, working levels over long periods of time the unmedicated group does better in the study. Much higher recovery rates, eightfold higher recovery rates, much less likely to be psychotic. The employment rates were dramatically different. 87% of those off medication had extended periods of employment, only something like 17% of the medication compliant. And one of the beauties of this study is this: The people who got off medication and did well, what do you think happened to them? Did they go back to their psychiatrists? They disappeared. Those who did well disappeared back into society. He found someone who became a professor, someone who became a lawyer, someone who became a high school teacher, and when they reentered society and became successful, none of them publicly identified as having had a diagnosis of schizophrenia. So he says we lose sight of these good outcome patients. In 2008 he presented his data to the American Psychiatric Association, here's what he said, summarized: "I conclude that patients with schizophrenia not on antipsychotic medication for a long period of time have significantly better global functioning than those on antipsychotics." That's the best long running study we have and how many of you have heard of that study? It doesn't get promoted. It doesn't get into your newspapers. Why not? Because it really does go against the counternarrative that we're organized around that counternarrative. There's now been a randomized study in the Netherlands, they found that the group that was tapered off had twice the higher recovery rate. And by the way I wanna emphasize here, these are outcomes of the aggregate, that doesn't mean that nobody's doing well on antipsychotics, that sort of thing. It's outcomes in the aggregate, it's a big picture thing. Now when this book came out, and we're gonna finish here in a few minutes with an example of how I think science can lead us to a better way of care. When this book came out in 2010 I was treated as a heretic. It was a little rough. In my hometown newspaper the Boston Globe, the day the book came out there was a review from a Harvard doctor who compared me to an AIDS denier and also compared me to a South African dictator who by virtue of having denied AIDS had caused hundreds of thousands of people to die and that if you read this book, that's the sort of danger you will incur. But that was five years ago. We now have a randomized study, Harrows published his data, and I'm gonna read you something from the British Journal of Psychiatry, 2012. "It is time to reappraise the assumption that antipsychotics must always be the first line of treatment for people with psychosis. This is not a wild cry from the distant outback, but a considered opinion by influential researchers. There is an increasing body of evidence that the adverse effects of antipsychotic treatments are, to put it simply, not worth the candle." So that's a story, now we're gonna go on to a new paradigm and then I'll be quiet here. But what do you see in this counternarrative? You see a story told through history and science, this is not science gathered by the critics, this is the science that was done by the NIMH, mainstream science, and basically what it did was illuminate a paradox that was not visible. And the challenge is, when do you start seeing real improvement in the unmedicated cohort? Two years, three years, four years. So in other words, how do you get people to that two year mark where you can really start seeing some actual healing? I believe ... In this book I also looked at what's the effect of antidepressants on the longterm course of depression, the effect of benzodiazepines on the longterm course of anxiety disorders, I look at where all the bipolar patients are coming from because the prevalence of bipolar has jumped dramatically, and also looking at what are we finding about longterm outcomes for children diagnosed with ADHD and treated with stimulants. I believe there is an increasing body of evidence that unfortunately, because of this oppositional tolerance program, and you can read a paper by Reef al-Malik, a formed mood disorders person at the University of Illinois, is that drugs that are effective over the short term because A, we don't know the pathology, and because of this oppositional tolerance that develops, you have two problems related the oppositional tolerance. Once on for a long time, it becomes hard to come off, but even if you stay on a longterm, you're gonna see a lot of increased risk of chronicity. So for example, treatment resistant depression, the percentage of patients now suffering from treatment resistant depression has risen from about 10% to 40% in the SSRI era. And by the way, the disability numbers, they're actually not being driven by psychotic disorders, it's affective disorders. It's a rise in depression and a bipolar disorder that is really driving that numbers in country after country. What I believe you need a lot more research into this, a lot more investigation of this, but what I'm trying to tell you here tonight, it's not just me who's saying this. You can see in the literature itself people worrying about this. Are we increasing the chronicity of these disorders. And at the very least, if there's a worry out there and you have 20% of your population on these medications and you're medicating kids, you wished society would at least investigate it in a full open manner, which we're not doing so much. But where might this lead? Could we do a better job? And the beauty of the antipsychotic story is there's a community in northern Finland, in Tornio, that in 1992 reconceptualized how it was gonna deal with psychotic patients. I don't have time, but it came out of a national experiment and basically in northern Finland they developed something called open dialogue therapy. Now the first thing they did do, whether right or wrong, is reconceptualize what the problem is. They say the problem does not reside in the brain of the person who's psychotic, but the in between spaces of people, like there's a social disruption, people get isolated and afraid to be with others. So our job, among other things, is to repair that in between spaces. So they believe they have to treat social systems and not just the individual. And in terms of how they use antipsychotics it goes like this: When people come in they try to avoid using antipsychotics with first episode patients. They do use benzodiazepines however to restore sleep, they think that's important. And then they have something, a measure called Grip on Life, and as long as a person's grip on life is improving a little bit, that means maybe they're showering, they're more willing to come and engage in discussion and all, they'll avoid using neuroleptics. But if someone's not getting better, they will use neuroleptics, antipsychotics, they try with low doses, and then after a period of time, after about six months of a person on an antipsychotic, they have another moment in their protocol where they see who can taper off. So it's a best use model, it's not an anti-use model. It's trying to figure out for whom and for how long. And here they've done this now three times, five year results. At the end of five years, 67% of their first episode patients had never been exposed to antipsychotics. 13% have been exposed temporarily, and 20% are on them longterm. What are their outcomes? At the end of five years, 80% of their first episode psychotic patients are asymptomatic and working or back in school. Only about 20% have really become chronically ill. And the other amazing thing that has happened in this corner of Finland is this: This is a population of about 70,000 in western Lapland and before they embrace this form of care, they had about 27 new cases of schizophrenia per year. If you do the numbers that's a lot of new cases of schizophrenia per year. It was one of the highest sort of prevalence rates in all of Europe. They're now down to about three new cases of schizophrenia per year. So why the drop? Well in fact, the eruption of psychotic episodes hasn't diminished much in that society, but what happens now with this new form of care, to get a diagnosis of schizophrenia you're supposed to be psychotic for six months or longer. People aren't staying psychotic long enough to move on to this schizophrenia diagnosis. And so what they're saying is we're seeing a new possibility where psychosis, which we used to see as schizophrenia, is turned back into an episodic disorder for so many people. Now after I featured this open dialogue in Anatomy of An Epidemic, a foundation formed here in the United States called the Foundation for Excellence in Mental Health Care to sort of investigate and also fund pilot projects to see if we could replicate open dialogue here in the United States. There's now a couple open dialogue projects happening in Massachusetts. Open dialogue is now really being talked about. The National Health Service in Britain is funding an open dialogue replication initiative in the UK, Germany is now a government funded some open dialogue replication projects and Italy has a couple projects as well. So the beauty of this story to me is that if you really took a look at the evidence, you could think of a different way of using the medications and instead of one size fits all, try to figure out for whom and for how long the selective use model and that is now gaining some traction. So it's a story I think of a counternarrative actually having some effect. So we'll open to questions, I just want to emphasize one thing here. I've given this talk like 500 times in some version. I know it can be really upsetting. It does challenge a lot of things that people are taught. It challenges decisions that people have made, how to organize their lives, how to treat their children, all of that's really threatening. It challenges what many professions do as well. And I know that's hard to sort of adjust your thinking, and my only plea here is maybe if we can make this research better known, at least we can have a discussion and we can see what is possible. And I honestly do not think this is an anti-med talk at all, I think it's a pro-science talk and I think it's a how can we make best use of meds to really facilitate longterm recovery. And again, final thing is, I think medications have a place. There's evidence of short term efficacy, there's evidence of some people doing well on them longterm, but I do believe our current paradigm of care, this where you get onto drugs quite easily, is really causing us harm as a society. And I also think the DSM 3 model, which expands the boundaries and narrows the limits of normalcy and expands the boundaries of pathology to kids too, I think that diagnostic construct is doing us a lot of harm as well, so thank you. (audience applauds) - We now have time for questions. If you have a question please raise your hand and we'll come to you with a microphone. As always, priority for questions will go to students. - [Male Audience Member] Hi, thank you so much for coming and talking to us tonight. So you mentioned some of the criticism that you received sort of in book reviews and that kind of literature when you first published your book, as well as some of the evidence for these medications sort of earlier on. But I'm assuming that you've also received some pushback in sort of the scientific community and the scientific literature for these claims and again studies that have made similar claims that you're basing your arguments on. And I'm wondering in recent years what has been the strongest sort of literature evidence pushback against the kind of argument you're making and how do you respond to that? - Yeah, great question. So when you publish a book like this, I try to find those studies so that I wouldn't miss them, and I had mentioned Emmanuel Stip where I said I was looking for others, could they point me to such studies, and they could not. And so that's just what I was expecting. One reviewer, one person who blurbed the book, a psychiatrist named David Healy in Wales said okay now it's up to psychiatry to make its response, where's he wrong? And then point to the studies, don't just say I'm a jerk. Well the amazing thing, it's been six years and it really hasn't happened. And a couple things, there's one study, you can read a thing by Allen Frances that's just out where he is now newly saying here's where we know antipsychotics work okay? And so there is this coming out. And what he'll point to again is the relapse studies, so he points to the relapse studies, and then he points to a study that has been done in China, it's a naturalistic study where they went into a community and they identified a group of people, average age 48, who had never been treated with schizophrenia. So they said here's our group of people that are actively psychotic, they've been psychotic for 13 years and they've never been in treatment, and then they followed that group of people for another 20 years and pretty much they stayed psychotic. And then they had as a comparison group a younger group that did get some medication and they were less likely to be psychotic 20 years later than this older group. And they said see that's what happens to untreated patients. And by the way when I was in ... There's a complicated answer to this. One of the real nice things, there was all this criticism initially, but then what happened was in fact I've been invited to give grand rounds at a number of psychiatry departments. Well why have I been invited to give grand rounds? Because this is not my research, I just think I'm the messenger, I'm saying look go read your own studies and go put it up. So in that way it really stood the test of time. I was asked to speak for the Group for the Advancement of Psychiatry, often very inhostile environments, but nevertheless it was happening. But it's still going on, there's this Chinese study that's now being presented as this shows you you need to treat people with antipsychotics. So what do you think about that study? Is there any flaw with that study? Okay, I come into a community of Chinese people, it doesn't matter if it's Chinese or not, and I come to you and I say can you point out your crazy people to me? I'm just using the language. And they say yeah these are our crazy people. And I find a bunch of people that have never been treated, they're 48 years old. Now imagine I had a psychotic episode when I was 22, someone did, and I recovered from that. Am I still among your crazy people? I'm not. You're self selecting for people who didn't recover. You're identifying the chronic group, that's the problem with that study. And even they admit that the group that was treated at some point is a different group, it's younger, et cetera, et cetera. Oh by the way, you wanna hear the kicker of the Chinese story? So the untreated group, yeah they stayed psychotic. What was the employment rate? 85%. So they concluded that being psychotic in this part of China did not keep you from working. And I felt like saying well maybe that's not so bad. (audience laughs) But here's the point. This book comes out, I feel vulnerable as can be, right? I'm not a doctor, I'm not a researcher, I'm not even a professor, I'm just a journalist, I'm just a messenger, and I'm holding up saying I think you need to look at this. So I'm vulnerable as can be right? And I'm waiting for the one that really makes me feel I screwed up, I missed something. But it's been six years and it hasn't been pointed out and they're going back to the relapse studies and there's this Chinese study and that's it. I'm like the energizer bunny, you ask me a question and I just keep going. But early on I was asked to give a keynote talk at something called The Alternatives Meeting, which is a meeting funded by the federal government but for user groups, okay? So they invited me to give the talk. And then there was some unhappiness apparently, and the group that invited me was told to disinvite me. You can't have this guy speak. So at this point the user group say this is our conference, invite him. And I got invited with this caveat: You'll give your talk, and then we'll have a psychiatrist say where you're wrong, sort of denounce you, and then you won't be allowed to respond. (audience laughs) So I said wow that's a great invitation. But you know I said this is really great, because now I'll see. Because this is going to be the chance for psychiatry to present its story. Anyway, they picked a person to give their talk who really wasn't much a researcher, so he went to an academic research community and they said look at Whitaker's stuff. Tell me where he's wrong and tell me where we have this evidence for longterm outcomes. And I was leaked the response to this investigation. The response was this: we've checked out all his citations and unfortunately he's very accurate. (audience laughs) And then basically, you know what the response was? And I'm not making this up. The response was yeah maybe there is a problem longterm, but that happens with all medical therapies, that the unmedicated group does better longterm. And people are going I didn't know that! And then really his complaint was, I'm not kidding this, he said: Whitaker's like a guy driving on the freeway and he just likes to point out the accidents. He needs to point all the people driving well down the road. That really was the response. So your question is so to the point. And the vulnerability I felt in 2011, the uncertainty, it's actually gone away a lot, because now you hear even Tom Insel, the head of the NIMH saying uh oh, we have a problem, maybe these drugs impair longterm functioning. You have the British Journal of Psychiatry saying uh oh, you have a randomized study. So I would like to be able to tell you that I feel now more vulnerable, because that would seem so, you know here's what I'm missing, but I really haven't seen it. And since the book came out you have people writing about target dysphoria, you've had people studying why drugs may be antidepressogenic longterm, so it's even moving more into the mainstream conversation. Not to the public, but in the research literature you see it happening. - [Male Audience Member] Hi Mr. Whitaker, thank you for coming to the Athenaeum. This question might be somewhat tangential. So I was kind of actually interested in seeing in your book, 'cuz I haven't read it yet, whether or not you had done any research into the effects of ketamine on longterm depression, because there's new research coming out saying that it works better than the standard SSRIs and things like that, and whether you had done any research regarding psilocybin mushrooms and LSD in treating depression and anxiety because we had somebody come to the Athenaeum when I was a sophomore who actually discussed the effects that it had on the medication that the government had deregulated the study of those kind of substances on depression and anxiety, so I was wondering if you had done any research into that regarding your book? - Yeah, first of all of course, I don't do research. I just read the studies basically, and that's really what I'm trying to do from a journalistic point of view, what is the research showing. I believe on the ketamine stuff, I'm not quite sure on this, but I thought they were now finding that the ketamine effects don't last beyond about 30 days. I think that's what I ... You might know this better than I do, but I thought that's what I read recently, that you're seeing this sort of immediate sort of response, but maybe not lasting in any sort of long way. And ketamine of course can have some pretty ... You know it can cause psychosis, that sort of thing. Maybe not in the doses they're using, I don't know, but ketamine of course had a use as a street drug. As far as LSD, of course there was some time in 50s and 60s they were using this as a possible therapeutic agent then with the war on drugs it gets seen as a horrible drug. I don't know where the current research is with LSD and psilocybin, I just don't know. - [Male Audience Member] Hi! First of all, thank you for coming. I was wondering, 'cuz you brought up ADHD in medicine briefly, have you actually looked into, or come across I guess, any research on ADHD medicine where early exposure led to a predisposition for addiction towards other drugs in adults? And if so, I was wondering if you had any ideas on how to remedy the situation. Perhaps like what they did for Finland in treating psychosis and such. - You all heard that question? The question does early exposure to stimulant medication predispose to later addiction to drugs? This is a really contentious area of research. There was a woman in California, who I forget her name unfortunately, who did a longterm study on this. It was a prospective study, and I forget her name on this, but she did announce that around 1999 or 2000 that it did ... The early exposure to stimulants did lead to greater substance abuse when they reached an adult age. Now there's a mechanism for this. Of course stimulants are dopamine releasing drugs, right? We like dopamine release. So often dopamine releasing drugs can be addictive, I mean cigarettes release dopamine as well. Then in response to her findings, there was some research done, I believe by Joseph Biederman at Massachusetts General Hospital and some others, who said no it's not true, we're not seeing this. And all I can say is the first was funded by the NIMH and Joseph Biederman and some of those who then said it wasn't happening did have close ties to pharmaceutical companies and the makers of stimulants. All I can say is it seems to me that it's a question that needs more investigation now, considering the prevalence with which we're diagnosing and medicating kids. I do also know that there's some worries about how early exposure to stimulants and regular exposure to stimulants effects the dopamine system longterm in youth. The worry, and some of this comes from rat studies, is if you have an agent that releases dopamine your brain in response is gonna dial down its dopamine machinery, which is the rewards system, and the worry is that in adults you might be creating youth that are less curious, that sort of thing, because they're just not as responsive because of the sort of dialed down dopaminergic machine. That's what they see in rats, but I have not seen any real research into that in humans. I think really what your question goes to though is if we're medicating say 7%, 8% of our kids with stimulants, we really wanna know what's happening to them as adults on substance abuse, other sort of questions and unfortunately we just haven't done the research we need to do on it. I will tell you, the best longterm study of stimulants was called the MTA Multimodal Study, lasted six, eight years, and they found no benefit of medication longterm on any domain of functioning from that particular study. - [Male Audience Member] Thank you for coming. I was just wondering about your comparison between developed countries and nondeveloped countries. I'm from a nondeveloped country, and I was just wondering if it seems like the difference between both countries has to do with the percentage of people who are diagnosed and put on these medicines. So I was wondering in developed countries what is influencing the prevalence of diagnosing people and giving them medicine? Is it big pharmacology? Is it the science behind it that's actually backing this up? Or what's going on? - Yeah, of course in that particular study everybody was diagnosed, so it doesn't have to do with different countrywide diagnostic rates. But why are so many people getting diagnosed in the United States for example? Why have we had this explosion of people diagnosed, an explosion of use of medications? Well you have to look at it partly really from a commercial point of view. The diagnoses in the DSM are constructs. In other words, people sat together and said here's where we'll draw a diagnostic line and one of the things that for example they did in DSM 3 is they really ... For say example with depression, historically, and this goes back to the Greeks. Depression was really understood to be of two types. There was a depression that could occur in response to life events, and that was seen as normal, not pathological. And then there was melancholy, or depression that could really set in that seemed out of proportion to life events or went on too long, et cetera. And it was only the latter which was really seen as a disease state, not the former. But what they did in DSM 3, they basically said you're gonna diagnose depression just by symptoms. Are you not sleeping, do you have some dysphoria, that sort of thing, and they have a list of nine symptoms. If you have five, you got it, and no longer were they making an inquiry into life events and what that really ultimately had the effect of is bringing all these people with more normal distress, sadness, having difficulties in life, into the diagnostic construct where now they can get diagnosed and treated with a medication. So one of the things you have is an expansion of diagnostic boundaries, beginning with DSM 3. So where we're gonna set the boundaries for normalcy, we're going to narrow those and we're gonna expand the boundaries where we can diagnose, okay? Now if you look at money going to those who do the diagnoses, there is pharmaceutical money going to many of the people on the panels, et cetera. And what do pharmaceutical companies like? They like boundaries that are big, 'cuz now they have a bigger audience, a bigger potential market. So what you really see, I believe, why we have so many people diagnosed and treated is you have a guild, a profession, that expanded its diagnostic boundaries and by doing so in fact asserted a domain or authority over a larger segment of the population, starting with kids, and then you had a pharmaceutical industry that has exploited those expanded diagnoses with great facility. And I think the result has been an extraordinary commercial success. I mean think about it, it went from 800 million to 40 billion dollars. From a commercial point of view, that is great success, and if you've converted 20% of the American population to daily use of psychiatric drugs, and often more than one psychiatric drugs, any business would love to have 20% consuming your product every day. So from a commercial point of view it's been a tremendous success. And I think that's a big part of it. - [Male Audience Member] Hi, other than the open dialogue therapy you talked about in Finland, are there any other nonpsychiatric treatments older therapies, newer therapies, even like less formal treatments like mindfulness-based therapies that you've seen as promising? - Sure, so one of the things you heard in the introduction was that I run this website called madinamerica.com and one of the things we do is we have a regular research news, summaries of news, that is constantly reporting on exactly what you're talking about. So for example, there's a recent report that if you look at psychotherapies over the longterm they tend to have better stay well rates. That's an example of that. You'll see in the UK for example now, you can go to your GP and get a prescription for exercise instead of getting a prescription for an antidepressant and that prescription you go to an exercise counselor, you get a free gym pass, they hook you up with other people to do green gyms, that's an example that is proving to be effective. You'll see some class interventions for example, there's a program called The Nurtured Heart approach that is being tried in schools in Tucson and I think San Francisco, and instead of trying to medicate the kids they try to change the environment of the classroom, especially in poorer districts. That's proving very effective. I've seen a food program in a school in Wisconsin that was very successful in reducing ADHD, the number of kids diagnosed. There's exercise, there are meditation programs, there's psychotherapy, CBT, so there's a lot of effort now in fact to find alternative modalities, whether they come from a psychotherapy background or sort of wellness programs. And I would say the research is really quite encouraging. And one of the things I wish I had said earlier is this is actually a good news story. I mean it's a bad news story in terms of the rising disability rates and all this, and the fact that so many youth frankly do see themselves in this new sort of way of seeing yourself, like 20%, 25% of kids arriving with a diagnoses. But what we're seeing in the research literature is a story of human resilience. Of a story sinking in the depression, sinking into mania, sinking into psychosis and recovering from those. Having the capacity to recover with the right types of support. So really the message here is, is there a way to build on that resilience and develop what you're talking about is modalities that really help nurture that resilience and maximize the possibility that an episode will be an episode and not turn into a chronic condition. - [Moderator] Unfortunately that's all the time we have for questions tonight. Please join me in thanking Mr. Robert Whitaker. (audience applauds)
- Thank you.
