Bipolar disorder and its biomythology: An interview with David Healy

David Healy, a former secretary of the British Association for Psychopharmacology, is the author of over 120 articles and 14 books, including The Antidepressant Era, The Creation of Psychopharmacology, and Mania, a fascinating new book on the history of bipolar disorder. His criticism of drug-company practices has put him at odds with colleagues in psychiatry and pharmacology. At the same time, his undisputed expertise as a leading academic, researcher, and clinician gives him a unique perspective on patterns and problems in Anglo-American psychiatry. He recently agreed to answer a number of questions about the growing prevalence and expanded definition of bipolar disorder.

Part of what you describe in your new book Mania: A Short History of Bipolar Disorder is a fair amount of "biomythology" about the illness. What aspects in particular do you have in mind?

Biomythology links to biobabble, a term I coined in 1999 to correspond to the widely-used expression psychobabble. Biobabble refers to things like the supposed lowering of serotonin levels and the chemical imbalance that are said to lie at the heart of mood disorders, ADHD, and anxiety disorders. This is as mythical as the supposed alterations of libido that Freudian theory says are at the heart of psychodynamic disorders.

While libido and serotonin are real things, the way these terms were once used by psychoanalysts and by psychopharmacologists now—especially in the way they have seeped into popular culture—bears no relationship to any underlying serotonin level or measurable chemical imbalance or disorder of libido. What's astonishing is how quickly these terms were taken up by popular culture, and how widely, with so many people now routinely referring their serotonin levels being out of whack when they are feeling wrong or unwell.

In the case of bipolar disorder the biomyths center on ideas of mood stabilization. But there is no evidence that the drugs stabilize moods. In fact, it is not even clear that it makes sense to talk about a mood center in the brain. A further piece of mythology aimed at keeping people on the drugs is that these are supposedly neuroprotective—but there's no evidence that this is the case and in fact these drugs can lead to brain damage.

How does our understanding of "mania" differ today from earlier conceptions of the phenomenon?

Bipolar disorder itself is a somewhat mythical entity. As used now the term bears little relation to classic manic-depressive illness, which required people to be hospitalized with an episode of illness, either depression or mania. The problems that currently are grouped under the heading "bipolar disorder" are akin to problems that, in the 1960s and 1970s, would have been called "anxiety" and treated with tranquilizers or, during the 1990s, would have been labeled "depression" and treated with antidepressants.

How did we move so rapidly in the 1990s from a psychotherapeutic treatment model for children to a largely drug-related one?

I think a key factor in this shift has been the availability of operational criteria. These were introduced in 1980 in DSM-III, the 3rd edition of the Diagnostic and Statistical Manual of Mental Disorders. The idea was to bridge the gap between the psychotherapists, on the one hand, and the neuroscientists on the other. It was hoped that if both camps could ensure that patients met 5 of 9 criteria for depression, for instance, then at least the patient groups would be homogenous, even if the views on what had led to the problems weren’t.

It was still assumed, however, that there was a place for clinical judgment, so that a patient who met 5 of the 9 criteria for depression but had 'flu or was pregnant would be diagnosed as being pregnant rather than depressed. But in the face of company marketing, and with the advent of the Internet, clinical judgment has been eroded. Patients going on the Internet or faced with drug company materials now all too easily find that they meet criteria for a disorder and there is often nothing or no-one to tell them this is not equivalent to having the disorder.

In the extreme, I have had patients with highly social careers come to me and say they think they have Asperger’s Syndrome because they've been on the Internet and find that they meet the criteria for this when, in fact, almost by definition, such a person cannot have Asperger’s Syndrome. In the absence of clinical judgment there is a default towards a biological option and a drug solution. Criteria create a problem for which a drug is all too often the answer, in just the same way that measurements of your lipid levels create a problem that a statin is the answer to.

Operational criteria are interacting here with a certain loss of medical authority. It is not possible for a doctor today to say to a patient, "Based on my 15 to 20 years experience, you do not have PTSD," or whatever. She cannot say, "We do not need to continue this conversation; come back when you’ve had a medical training and 15 years of clinical experience."

The doctor has to engage with the patient on the level of the material that's out there in popular culture, and when she tries to do this she will find that she's up against an extraordinarily skilful deployment of those materials by pharmaceutical company marketing departments who are masters at populating the wider culture to suit their interests.

In the mid-1990s, you note, roughly half of all mood disorders were redefined as bipolar disorder rather than depression. What do you think accounts for that dramatic shift in perspective?

The key event in the mid-1990s that led to the change in perspective was the marketing of Depakote by Abbott as a mood stabilizer. Before that, the concept of mood stabilization didn't exist. And while in a popular TV series we can accept that Buffy the Vampire Slayer gets a new sister in Season Five that she had all the time but we didn’t know about, we don’t expect this to happen in academia.

The introduction of mood stabilization by Abbott and other companies who jumped on the bandwagon to market anticonvulsants and antipsychotics was in fact quite comparable to Buffy getting a new sister. Mood stabilization didn’t exist before the mid-1990s. It can’t be found in any of the earlier reference books and journals. Since then, however, we now have sections for mood stabilizers in all the books on psychotropic drugs, and over a hundred articles per year featuring mood stabilization in their titles.

In the same way, Abbott and other companies such as Lilly marketing Zyprexa for bipolar disorder have re-engineered manic-depressive illness. While the term bipolar disorder was there since 1980, manic-depression was the term that was still more commonly used until the mid-1990s when it vanishes and is replaced by bipolar disorder. Nowadays, over 500 articles per year feature bipolar disorder in their titles.

You just have to look at Lilly’s marketing of Donna from the Zyprexa documents on the Internet to see what is going on here: "Donna is a single mom, in her mid-30s, appearing in your office in drab clothing and seeming somewhat ill at ease. Her chief complaint is 'I feel so anxious and irritable lately.' Today she says she has been sleeping more than usual and has trouble concentrating at work and at home. However, several appointments earlier she was talkative, elated, and reported little need for sleep. You have treated her with various medications including antidepressants with little success. . . You will be able to assure Donna that Zyprexa is safe and that it will help relieve the symptoms she is struggling with."

Donna could have featured in ads for tranquilizers from the 1960s to the 80s, or for antidepressants in the 1990s, and would have probably been more likely to respond to either of these treatment groups than to an antipsychotic, and less likely to be harmed by them than by an antipsychotic. What company marketers are so good at doing is framing the common symptoms people have—we almost all have—in a manner most likely to lead to a prescription for the remedy of the day. It flies in the face of a century of psychiatric thinking to see conditions that patients like Donna have as bipolar disorder. But while a century of psychiatric thinking used to count for something, it doesn't any longer.

Between 1996-2001, you explain, there was a fivefold increase in the use of antipsychotics (Zyprexa, Risperdal, Abilify, Seroquel, and others) in preschoolers and preteens. What role did DSM-IV play in that, with its introduction of the still-controversial category Bipolar II disorder?

The concept of juvenile bipolar disorder flies even more in the face of traditional wisdom in psychiatry than does calling Donna bipolar. As of 2008, upwards of a million children in the United States—in many cases preschoolers—are on "mood-stabilizers" for bipolar disorder, even though the condition remains unrecognized in the rest of the world.

I am not sure how much DSM-IV played a role in this switch. I think the companies would have found a way to engineer the switch even without the introduction of Bipolar II disorder in DSM-IV.

So then how much of that shift is attributable to SSRI antidepressants coming off patent while the antipsychotics were still major revenue earners?

I think this was in fact central to what happened. The antidepressants were due to come off patent whereas the anticonvulsants were older drugs that could be repatented for this purpose, and the antipsychotics—which also could be (and were) marketed as mood stabilizers—were early in their patent life.

A related point that’s worth bringing out is that the switch happened because companies weren't able to make new and more effective antidepressants. Had they been able to do so, I think they would have probably stuck with the depression model rather than made the switch to bipolar disorder.

In terms of what is happening in the US, I think we have to look at how skillfully the drug companies have exploited doctors. Doctors have wanted to help. While the drugs are available on prescription only, doctors tend to see giving a medicine as the way to go, where previously they had been much more skeptical about the benefits of drug treatments.

The drug companies have engineered a situation in which academics have become the primary spokespeople for the drugs. We see the sales rep in the corner and think we can easily resist his or her charms—but we still let them pick up the drinks tab. But it's the academics who sell the drugs. Doctors who think they are uninfluenced by company marketing listen to the voices of academic psychiatrists when these, in the case of the antidepressants or antipsychotics given to children, have talked about the data from controlled trials, and by doing so have been witting or unwitting mouthpieces for company marketing departments.

In your opinion, did the FDA's 2004 decision to add black-box warnings to SSRIs over pediatric use lead to greater off-label prescriptions and even the move toward antipsychotics, on the presumption that the latter are safer to use on children?

I think this had very little effect on the switch from depression to bipolar disorder, but what was quite striking was how quickly companies were able to use the views of the few bipolar-ologists who argued that when children become suicidal on antidepressants it's not the fault of the drug. The problem, they said, stems from a mistaken diagnosis and if we could just get the diagnosis right and put the child on mood stabilizers then there wouldn't be a problem.

There is no evidence for this viewpoint, but it was interesting to see how company support could put wind in the sails of such a perspective.

It was also interesting to see how close to delusional people could get about an idea like this. Faced with details such as even healthy volunteers becoming suicidal on an antidepressant, committed bipolar-ologists were quite ready to say that this just shows that these normal people are latently bipolar.

In this case, I think most people will see that "latent bipolarity," as a concept, is functioning a little bit like the way latent homosexuality once functioned for the Freudians. Most people will also see that the first concept is impossible. What the companies have done is hand a megaphone to the proponents of that view on bipolar disorder, which was until very recently a distinctly minority one.

And are the antipsychotics in fact safer than antidepressants?

No, they are not. The antipsychotics are as dangerous as the antidepressants. Before the introduction of the antipsychotics, the rates of suicide in schizophrenia were extremely low—they were hard to differentiate from the rest of the population. Since the introduction of the antipsychotics the rates of suicide have risen 10- or 20-fold.

Long before the antidepressants were linked with akathisia, the antipsychotics were universally recognized as causing this problem. It was also universally accepted that the akathisia they induce risked precipitating the patient into suicidality or violence.

They also cause a physical dependence. Zyprexa is among the drugs most likely to cause people to become physically dependent on it. As far as I am concerned, Zyprexa's license for supposed maintenance treatment in bipolar disorder stems from data that is in fact excellent evidence for the physical dependence it causes and the problems that can arise when the treatment is stopped.

In addition, of course, these drugs are known to cause a range of neurological syndromes, diabetes, cardiovascular problems, and other problems. It's hard to understand how blind clinicians can get to problems like these, especially in youngsters who grow obese and become diabetic right before their eyes.

But we have a field which, when faced with the obvious, instead chose to listen to Eli Lilly voices saying, "Oh no, there is no problem with Zyprexa. The psychosis is what causes diabetes—Henry Maudsley recognized that 130 years ago." Well Henry Maudsley hated patients, and saw very few of them at a time when diabetes was rare. We recently looked at admissions to the North Wales Hospital from 1875-1924, years spanning his career, and among the more than 1,200 cases admitted for serious mental illness, not one had diabetes and none went on to develop it.

We also looked at admissions to the local mental-health unit between 1994 and 2007, and in over 400 first admissions none had type 2 diabetes, but the group as a whole went on to develop diabetes at twice the national rate.

This is not surprising. What is is how the entire field swallowed the Lilly line, especially when it was so implausible to begin with. We had great difficulties getting this article published—one journal refused even to have it reviewed.

One way of raising the profile of bipolar disorder in children, you note, was to argue that they'd been misdiagnosed with ADHD. What were the implications and effects of that claim?

In the case of children with ADHD, I think what one needs to appreciate is that in most of the world until very recently (and in countries like India still), ADHD is a very rare disorder where children, usually boys, are physically very overactive. This is a condition they grow out of in their teens. Treatment with a stimulant can make a difference in cases like this. Whether treatment is always called for, however, may depend on the circumstances of the child as opposed to the nature of any supposed condition.

It is only in a world where schooling or adherence to a particular set of social norms is compulsory that a condition like ADHD becomes a disorder. There was greater scope over a century ago than there is now for children to do other things in childhood and wait until they settled down in adolescence without being treated for their condition.

What we have today is not ADHD as it was classically understood, but rather a state of affairs we have had for centuries, which is "the problem child." Today the problem child is labeled as having ADHD. But having just one label is very limiting. Child psychiatry needed another disorder—and for this reason bipolar disorder was welcome.

Not all children find stimulants suitable, and just as with the SSRIs and bipolar disorder it has become very convenient to say that the stimulants weren't causing the problem the child was experiencing; the child in fact had a different disorder and if we could just get the diagnosis correct, then everything else would fall into place.

One fascinating phenomena at the moment is a clear looping effect with adult ADHD. Quite recently Britain's NICE [National Institute for Health and Clinical Excellence] guidelines for ADHD came out and stated that adult ADHD is a valid clinical disorder. I am quite sure that a few years ago, 85 to 90 percent of physicians in the UK would not have thought adult ADHD was a valid clinical disorder. One might expect guidelines to be somewhat conservative, but in this case what we appear to be seeing is the guideline process getting out ahead of the field, leading clinicians in a direction that seems to be quite surprising.

Drug companies understand all too well that those constructing guidelines are supposed to be value-neutral and to follow the data. This means they can readily engineer trials that may show minimal benefit for their drug for a condition they have called "adult ADHD." The makers of the guidelines have little option but to suspend judgment and to accept that the condition named must be real. So, for instance, as Lilly grasped, they end up endorsing the use of the agent like Strattera.

What's astonishing about the current situation is that there seems to be almost no way to get the guideline makers—who are sitting in the middle of the road, immobilized by the oncoming headlights—out of the way of the pharmaceutical juggernaut. You can point out how they are being manipulated but they shrug and ask, "What can we do?"

We have recently begun a survey, here in North Wales, looking at aspects of this situation. In response to questions, clinicians here have indicated that three years ago they were quite certain they would not have used adult ADHD as a valid condition, but that three years from now they anticipate that they probably will. I think this shows a realistic appreciation of company abilities to change the climate in which clinical practice takes place, and the relative futility of attempting to stand up to such changes.

You have to treat real patients. What do you tell them about these conditions and their treatment options?

Many clinicians, scientists, and patients have heard about postmodernism. They might have heard company criticism of someone like me along such lines as "Pay no heed to him, he's just a postmodernist." The implication is that postmodernism is all-but a psychiatric disorder in its own right, in which academics like me refuse to concede that there's any reality to human behaviors—or the physical underpinnings of disorders of human behavior. By contrast, the story goes, there are the hard scientists who work in or with drug companies who deal only with facts and hard data, and the proof is that they bring new and helpful drugs to the market.

Well, I think what Donna's story above illustrates is that pharmaceutical marketing departments are actually the postmodernists par excellence. They treat the human body (including its disorders and complaints) as texts to be interpreted one way this year and in just the opposite way a year or two later.

In contrast, when it comes to the hazards of these drugs—just like the tobacco companies before them—the motto of Pharma has become "doubt is our product"—they simply refuse to concede that their drugs are linked to any hazard at all . . . until the drug goes off patent. You cannot get a better definition of postmodernism than "doubt is our product."

So, to the matter of whose treatments are better: I'm quite happy that the patients coming to see me would in general get more effective and safer treatment for their problems than they'd get from physicians adhering to the latest guidelines. Trouble is, I only have to slip up once to have a big problem, whereas atrocities can be committed on the other side without anyone likely to be affected by blowback.

David Healy is the author of 14 books, including The Antidepressant Era, The Creation of Psychopharmacology, Let Them Eat Prozac: The Unhealthy Relationship between the Pharmaceutical Industry and Depression, and, most recently, Mania: A Short History of Bipolar Disorder. Christopher Lane is the author most recently of Shyness: How Normal Behavior Became a Sickness.