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 [1] 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 [2] 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 [3].
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 [4].
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 [5]. Christopher Lane is the author most recently of Shyness: How Normal Behavior Became a Sickness. [6]
Links:
[1] http://www.bmj.com/cgi/content/full/318/7188/949/a
[2]
http://www.furiousseasons.com/archives/2007/02/the_zyprexa_chronicles_marketing_zyprexa_as_the_new_mood_stabilizer_for_bipolar_disorder_and_downpla_1.html
[3] http://bjp.rcpsych.org/cgi/content/full/188/3/223
[4] http://www.biomedcentral.com/1471-244X/8/67
[5]
http://www.amazon.com/Mania-History-Bipolar-Disorder-Biographies/dp/0801888220/ref=sr_1_1?ie=UTF8&s=books&qid=1239908094&sr=1-1
[6] http://www.amazon.com/Shyness-Normal-Behavior-Became-Sickness/dp/0300143176/ref=ed_oe_p