'Mind Fixers' Documents The 'Troubled Search' For Mental Illness Medication

TERRY GROSS, HOST:

This is FRESH AIR. I'm Terry Gross. The search for a biological understanding of mental illness, including schizophrenia, bipolar disorder, depression and panic disorder, is the subject of the new book, "Mind Fixers," by my guest, Anne Harrington. She writes about the revolution in medications to treat mental illness and why it's left behind what she describes as an unsatisfactory legacy of overdiagnosis, overmedication and promises that were unfulfilled. Harrington is a professor of the history of science at Harvard and director of undergraduate studies in the history of science. She specializes in the history of psychiatry, neuroscience, and other mind and behavioral sciences. For six years, she directed Harvard's Mind, Brain and Behavior Initiative.

Anne Harrington, welcome to FRESH AIR. Let's talk a little bit about depression and antidepressants.

ANNE HARRINGTON: OK.

GROSS: I think the real game-changer here was probably Prozac in the 1980s; that became a hugely popular drug. And what was groundbreaking at the time, when Prozac came onto the market?

HARRINGTON: So the irony of Prozac's blockbuster success was that its manufacturer, Eli Lilly, didn't really expect much from it. So Prozac goes on the market, and because it's been framed as safer, people start prescribing it. General practitioners and psychiatrists are prescribing Prozac over other brands, and they also start prescribing it to patients to whom they might previously have hesitated to prescribe what would be perceived as a more dangerous tricyclic antidepressant.

So the market for this antidepressant grows in part because the patient pool to whom it's being prescribed grows enormously. And an important subset of that patient pool are patients who previously might have been given a prescription for Valium.

GROSS: So why does the patient pool grow?

HARRINGTON: Well, because patient - there had been an enormous market for anti-anxiety medications. And Valium, in the 1970s, became - was at that point - in, like, 1978, I think there was something like - 2.2 billion pills of Valium were sold in one year. It was the bestselling prescription drug of all time in the 1970s. And it was an anti-anxiety medication, but then it turned out it was addictive; people couldn't get off it. The market for the benzodiazepine plummets. But where are these people - what are we going to do for these kinds of patients?

Well, it had long been known that one of the symptoms of depression was often anxiety. And so it became possible to think, well, maybe these patients who were previously being diagnosed with anxiety in fact suffer from depression with acute anxiety presentation, and maybe the antidepressants will help. And they did. And so you've got, you know, the expanding pool of people suffering from depression. You've got the emergence of depression in the way we think about it now, as the common cold of psychiatry.

You've also got a development in which there's a collapse of a previous distinction that the field had made between forms of depression that should be treated medically and forms of depression that were seen to be neurotic or reactive, that were caused by bad stuff going on in your life, and that it was widely thought should therefore be treated with talk therapy. But if medication helps everybody, then maybe these distinctions, some say, aren't so important; maybe what's more important is the severity of the symptoms. And at some point, the symptoms are severe enough, medication might then be what you choose to prescribe the patient.

GROSS: So you've got a lot going on there. You've got this new drug, Prozac, that's supposed to, you know, address depression. You've got patients with anxiety who are being recategorized as having depression with anxiety as a kind of side effect of the depression. They're getting prescribed Prozac, too. And at the same time, you have new literature coming out, like, "Listening To Prozac," the bestselling book by Peter Kramer, that asks the question, you know, like, if Prozac is so effective and it's basically remaking people's mood and mental health and changing them, like, what does that mean if people can be changed by pills, even if it's change for the better? Like, existentially, what does that mean? But in the long run, how effective was Prozac, or is Prozac?

HARRINGTON: The huge developments that happen in the story of depression and the antidepressants happens in the late '90s, when a range of different studies increasingly seemed to suggest that these antidepressants, although they're helping a lot of people - they seem to be helping a lot of people - when compared to placebo versions of themselves, don't seem to do much better. And that is not because they are not helping people, but because the placebos are also helping people; that simply thinking you're taking Prozac, I guess, can have a powerful effect on your state of depression. In order, though, for a drug to get on the market, it's got to beat the placebo. If it can't beat the placebo, the drug fails.

And so I think the whole SSRI story - because of course, there wasn't then just Prozac. There was then Paxil, and there was Zoloft. There became a whole family of these drugs. They all are now off-patent. And I think that the world of antidepressants is also looking for some new novel chapter. I think it's also hit a kind of standstill.

GROSS: Do you think those drugs are getting prescribed as frequently or perhaps more frequently than they were in the '80s, when Prozac was new and was seen as - and this, like, groundbreaking drug?

HARRINGTON: Well, there was a glamour moment. We became a Prozac nation. Peter Kramer contributed to the - I think unintentionally, because his goal was actually to be rather critical rather than celebratory of what he said were Prozac's effects. But he implied that Prozac was a drug that not only normalized but enhanced, and that therefore we would be seeing people taking these drugs not because they necessarily had a diagnosable disorder but because it would give them an edge or lift their mood or help them become the kind of person they would prefer to be.

And he said, you know, we - maybe we're worried about this, maybe we don't like it, but let's not be naive; this is what's going to happen, and we need to grapple with it - that was his argument. But it was taken to be a kind of endorsement of a kind of legal street drug culture, in which people are on Prozac for trivial reasons or for hedonistic reasons or for professional advancement reasons. I think we're past that moment. I think people still go on SSRIs. I think there's a more sober, in general, sort of set of calculations that are undertaken. I think people are more aware of side effects and the difficulties of getting off long-term use.

GROSS: In writing about the biology of mental illness and the drugs that have been created to address it, you write some about the marketing of those drugs. And let's look at one of the really successful marketing campaigns, and that would be for Xanax, which was approved by the FDA in 1981. And that coincided with the end of the diagnosis of anxiety neurosis and the addition in the DSM of the diagnosis of panic disorder.

HARRINGTON: Mmm hmm.

GROSS: So how is Xanax marketed to tie in to this new diagnosis of panic disorder?

HARRINGTON: So Xanax was originally going to be the next generation to valium. It's being tested and developed several decades before it finally gets FDA approval. In the interim, the market for drugs - benzodiazepines like Valium - largely collapses. In the interim, the disorder for which patients were being prescribed Valium - you know, neurotic anxiety - is deemed to no longer be a valid diagnostic category. The DSM comes out. And so now you've got a drug maybe as good as Valium, maybe better than Valium. But whatever it is, it's a benzodiazepine. And it doesn't have - the diagnostic category for which it was originally developed doesn't exist anymore.

But in the DSM, there are other, new forms of anxiety that are meant to be more targeted, that are meant to slice and dice more precisely the spectrum of anxiety, forms of anxious suffering that people suffer from. And one of these is a disorder that most people had never heard of called panic disorder. And there had been previous arguments and research suggesting that panic disorder has an biological substratum, that it's a genuine medical condition distinct from the forms of anxiety that the psychoanalysts used to see or that the GPs used to give patients Valium for.

Originally, it was felt, therefore, that the benzodiazepines weren't effective on panic disorder, that you should give them anti-depressants. But the makers of Xanax needed to sell Xanax. And they therefore took a second look at the possibility that their drug might be effective for panic disorder, not because they didn't think it was going to be more effective than, say, Valium might be, but they needed to sell Xanax.

And it is effective, and it gets approved by the FDA as the first targeted medication for a disorder that most people had, at that point, never heard of called panic disorder. And part of the marketing of all of these efforts to target often older drugs for new disorders is to educate or tell people about this disorder that they've not potentially ever heard of, persuade them to wonder whether or not they might suffer from them themselves and persuade them to discuss that possibility with their physician.

GROSS: So you had mentioned that the market for Valium had collapsed before the release of Xanax. Why was the market for Valium collapsing?

HARRINGTON: Because the growing recognition that benzodiazepines were highly addictive - there were a number of very high-profile kinds of cases - including Betty Ford, the wife of the president - of people who publicly confessed that they were Valium addicts and needed to go into rehab. It became perceived - whereas once, drugs like Valium were seen as kind of no more dangerous than having a pick-me-up cup of coffee in the morning - where it was seen as dangerous drugs, as addictive drugs.

GROSS: Is Xanax less addictive than Valium?

HARRINGTON: Good question. I don't know 'cause I'm not a clinician, but I can say that I - you know, you are now beginning to see some of the kinds of conversations about drugs like Xanax that you saw about drugs like Valium 40 years ago or so.

GROSS: Let me reintroduce you. If you're just joining us, my guest is Anne Harrington. She's the author of the new book "Mind Fixers: Psychiatry's Troubled Search For The Biology Of Mental Illness." We'll be right back after we take a short break. This is FRESH AIR.

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GROSS: This is FRESH AIR. And if you're just joining us, my guest is Anne Harrington, author of the new book "Mind Fixers: Psychiatry's Troubled Search For The Biology Of Mental Illness." She's a professor of the history of science at Harvard.

Let's talk about bipolar syndrome, which has its roots as a diagnosis in what was called manic depression. So, like, what is the difference between manic depression and bipolar? Are they the same thing, just renamed, or are they two separate diagnoses?

HARRINGTON: Some people use the term more or less interchangeably. The term manic depression was widely used until the 1980s to describe a form of mood disorder that classically involved cycling between experiences of great agitation or elevation, moods of great depression.

In the 1980s, the term bipolar disorder was swapped out in the DSM-III for manic depression. And it was swapped out, in part, because of some genetic research that some felt at the time showed clearly that there were two kinds of mood disorder. There was depression, which some people then suggested could be renamed unipolar disorder, and there was the disorder formerly known as manic depression that could then be called as - known as bipolar disorder. Not everyone agreed then or now with this bifurcation. And there has been a push among some clinicians and experts to reintroduce the more expansive category of manic depression disorder.

But I also think there was a feeling among the public - I mean, the number of the advocacy groups changed their name, also, and they didn't do it primarily only because of the genetic work. They did it because they felt that manic depressive disorder frightened people as a term, that bipolar disorder was a more sort of friendlier and less stigmatizing way of talking about this form of suffering.

GROSS: What was it about the words manic depression that sounded more frightening than bipolar disorder?

HARRINGTON: Well, I think man - mania and the maniac and - you know, it invoked sort of wild-eye, potentially violent forms of behavior, and that was not at all the kind of message that an advocacy organization would be wanting to convey. They didn't want people who were frightened - be frightened off from seeking help.

GROSS: So I think the first drug that was used to treat manic depression was lithium, which you write was previously marketed as a health tonic. That amazed me when I read it.

HARRINGTON: Really? The first thing to know about lithium to understand its strange place in the history of psychiatry is that unlike all the other drugs, it wasn't invented in a laboratory. It's an element. It's found in the natural world. And it's found, for example, in certain kinds of spas in Europe that, in the past, you know, bragged about their high lithium content of their drinking water. And so it had a place in spa culture. It had a place as a feel good tonic. It was, for a period of time, an ingredient in a new lemon-lime soft drink that became quite popular in - up through the 1950s that gets renamed 7UP. And there's a...

GROSS: 7UP had lithium in it?

HARRINGTON: 7UP had lithium in it, and there's - no one quite knows for sure why Griggs (ph), the inventor of this soft drink - it had a very convoluted previous name. But it was renamed 7UP, and some think that this might be a reference to the atomic number of lithium. It's just under seven and the up meaning the suggestion that it lifts the mood. Lithium is no longer in 7UP. Cocaine is no longer in Coca-Cola.

GROSS: (Laughter) Right.

HARRINGTON: But there was this previous history of lithium. And then lithium sort of fortunes as a product, and it's used in all sorts of other things too that have nothing to do with, you know, the health industry. But its fortunes as a product in the health industry take a nosedive when it is used as the basis - or a compound of lithium is used as the basis for a salt substitute that ends up, people believe, causing heart problems and even several deaths. And so there's a warning sent out by the AMA and then eventually FDA that, you know, these salt substitutes - take them off the market. This is a dangerous drug. And so lithium's emergence in psychiatry emerges against the background of two relevant facts. One, it has a reputation now for being dangerous and, two, it's not going to make a pharmaceutical company very much money because they can't patent it.

GROSS: So is lithium still, like, a drug of choice for treating patients with bipolar disorder?

HARRINGTON: I think there are a lot of people who say it's a very good drug. And there are some people who still take lithium. The problem with lithium - and I use the word problem, you know, it's not a problem for patients as much as it's a problem for the industry and the way in which the industry is a player in these - how things develop - is that it wasn't profitable. Certain clinicians had to basically go and petition several pharmaceutical companies to even market it after it received FDA approval in the 1970s. No one was interested in it. So what then happened is the drug companies found ways to make treatment for bipolar disorder more profitable by developing other patentable or proprietary drugs. And the first generation of these were drugs that have formerly been anti-epileptic drugs, drugs - names like Depakote - that they then called mood stabilizers. And now a lot of people are on the second generation or atypical antipsychotics that also in the '90s and beyond got FDA approval as treatments for bipolar disorder.

GROSS: So lithium was taken off the market as a salt substitute because of its side effects. But then, you know, lithium as a drug to treat manic depression or bipolar disorder, is it still seen as having the harmful side effects, possibly cardiac side effects?

HARRINGTON: Well, I think what does happen is that people incorporate a recognition that there is this risk, and there's - then people on lithium undergo regular blood monitoring and then adjustment of their dose to reduce the risk of a cardiac incident.

GROSS: My guest is Anne Harrington, author of the new book "Mind Fixers: Psychiatry's Troubled Search For The Biology Of Mental Illness." We'll talk more after a break. We'll also hear Maureen Corrigan's review of Janny Scott's memoir about growing up in a wealthy, mainline family in Philadelphia. Her grandmother was said to be the inspiration for Katharine Hepburn's character in the film "The Philadelphia Story." And linguist Geoff Nunberg will talk about a word we're hearing a lot now - socialism. I'm Terry Gross, and this is FRESH AIR.

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GROSS: This is FRESH AIR. I'm Terry Gross. Let's get back to our interview about the search for a biological understanding of mental illness and for drugs to treat it. My guest is Harvard professor Anne Harrington, author of the book "Mind Fixers."

So your book is about, basically, like, the history of pharmaceutical treatment for mental health disorders. And at the end of the book, you say that you think a lot of pharmaceutical companies have been leaving the psychiatric field. And I was very surprised to read that because it seems like just about everybody is on something...

HARRINGTON: Yeah.

GROSS: ...Right now. And why would pharmaceutical companies be leaving when so many people are on antidepressants or treatment for bipolar disorder, you know, not to mention antipsychotics? And it's hard to get off of many of these drugs, so once you're on it, you, like, tend to stay on them. So why would pharmaceutical companies be leaving?

HARRINGTON: Because there's been no new good ideas as to where to look for new, novel biomarkers or targets since the 1960s. The only possible exception is there is now some excitement about ketamine, which targets a different set of biochemical systems. But R&D is very expensive. These drugs are now, mostly, off patent. Their efforts, even to develop - for decades, they've been tinkering around the edges of the same kinds of molecular targets. And even their efforts to bring on new drugs in that sort of tried-and-true and tested way - with a tinker here and a tinker there - has been running up against mostly unexplained but indubitable problems with the placebo effect.

GROSS: The drugs don't seem to get better results than people getting a placebo.

HARRINGTON: That's right, but it doesn't mean that the drugs don't work. It just means that the placebo effect is really strong. But the logic of clinical trials is that the placebo effect is nothing, and you have to be able to be better than nothing. But of course, if the placebo effect isn't just nothing, then maybe you need to rethink what it means to test a drug. Now, this sort of goes beyond what historians should be talking about, but it does seem that the pharmaceutical company has a big placebo problem on its hands.

GROSS: You know, in talking about a new drug has to beat the placebo in test trials in order to be approved by the FDA...

HARRINGTON: Yep.

GROSS: ...I'd love to hear more research about the placebo effect. It obviously exists. (Laughter) We should find a way of harnessing it better (laughter).

HARRINGTON: Well, I agree with that. Before I wrote "Mind Fixers," I'd spent quite a bit of time being interested in the placebo effect as a really interesting and understudied and under-theorized entity in its own right. And I followed the research of people who are trying to show this. Look; there's a biology of the placebo effect, and if you give people fake morphine, you know, you can see changes in their brain. If you give people fake antidepressants, you can see changes in their brain. So there's a real biology here. And yet I think the tempting conclusion that, well, why don't we just give people placebos if they're so good? - is a dangerous one.

GROSS: Well, you'd be lying to them. You'd be telling them it's a drug when it's not.

HARRINGTON: Well, that's - some people say, oh, you can get around that by telling people that, you know, we found these drugs - this is a drug with no side effects because it's got no active ingredients, and we found it to be very effective. Evidence shows it's effective in people with your condition. But I think that the placebo effect is as powerful as it is because it's parasitic. Our beliefs in - it's parasitic on the pharmaceutical industry. People don't believe in the placebo effect, and I don't think any amount of reframing is going to profoundly change that. People believe in medicines, and so, you know, you just have to see why the placebo effect is likely, on its own, not going to be our solution. You just have to go back to a world before these pharmaceuticals came on the market, before we had drugs, and ask any older psychiatrist, who remembers those years, what it was like.

Now, where I do think that there's a lot of room to pay more attention to the placebo effect going forward is in the ways in which it's present even when you're taking an active drug. There's always a placebo effect. The placebo effect isn't just the effect of a fake drug. It's just that we can see it more clearly there when there aren't other confounding factors. There's always a placebo effect, and the placebo effect also points us to the ways that we're more than just biochemical systems - in the narrow, reductionist understanding of the word, that we respond to a relationship with a doctor. We respond to what we're told when we're given the medication. We respond to going to this hospital rather than some other hospital because we read in the U.S. news and whatever report that it's a great hospital. Or we read something different about it. It reminds us that biochemistry is not all there is. It does offer and open up the possibility of, I think, a more interdisciplinary and more holistic way of thinking - even about drug treatment.

GROSS: So you teach at Harvard, and you've been teaching how many years?

HARRINGTON: Oh, over 20.

GROSS: So in that time - I doubt you ask students if they're on medication, but maybe there's a way you can kind of get a sense of that - do you think that the number of students on various mental health and anti-anxiety disorder medications has increased or decreased over time? And do you think attitudes among your students, you know, have changed about those medications?

HARRINGTON: So I have both been teaching at Harvard for over 20 years with teaching large undergraduate courses, including courses on the history of psychiatry, so I get a lot of students who come with histories. It's why they're drawn to the course. I also, though, lived with undergraduates. I'm what's called a faculty dean of a residential community on the Harvard campus, and so I get to know these students personally. And I - when they have problems and struggles and anxieties, you know, I'm sort of listening and there. And so - and my impression is that, yeah, I think that they're more fragile. They feel more fragile to me.

But I also know that when - 10 years ago, I wasn't living with them. So I - may just be the fact that I now see more up close how fragile they feel, how much they struggle. And I think that a lot of them are on medication. I think that the reasons they're on medication sometimes are probably medical and sometimes are because it will help them, even though they don't necessarily, in my non-clinical view but just knowing them as people, you know, it's - that it will help them get through. And I have come to believe that, you know, there are reasons sometimes to go on medication that are not simply because you have a biochemical imbalance or you have a - some kind of biological defect.

GROSS: So are you saying that there's times in the lives of the students where they benefit from medication, even though they don't have, like, a diagnosed disorder?

HARRINGTON: But let me try to say this carefully because it's important. A person can be depressed. A person can be hugely anxious. And the reasons that a person is deeply depressed or hugely anxious sometimes is not discernable and sometimes is discernible. We don't know enough about the biology of these mental disorders to know whether or not, you know, some of the reasons are biological - in the sense that medicine likes to think of these things as diseases - and whether it's just because they're having terrible problems. You know, their family at home is just struggling. And they're having trouble concentrating on their homework, and they're not doing well in school. And they can't - you know, and they get more and more despairing.

Are they - do they have a disease? Do they - I don't know. Do they need help? Yes, I think they do. What are the options available to them? Well, I would love to see a larger, more pluralistic set of options. But I do - have come to believe that medication sometimes might want to be one of them. But again, it comes back to what we were saying before. There needs to be a honest risk/benefit assessment that includes the person who's being - going to take the medication. I'm so - it's so important that, you know, we're - involve the patients, the people who are on these drugs in the conversations and talk to them about what - why this might help, what we do or we don't know and move forward in our imperfect world to try to deal with the suffering.

GROSS: Anne Harrington, I want to thank you for talking with us.

HARRINGTON: Thank you very much for having me. I really appreciated the chance.

GROSS: Anne Harrington is the author of the new book "Mind Fixers." After we take a short break, Maureen Corrigan will review a new memoir by Janny Scott about growing up in a wealthy Philadelphia family. It's called "The Beneficiary: Fortune, Misfortune And The Story Of My Father." This is FRESH AIR.

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