Cracked (8 page)

In other words, despite the damning research about antidepressant efficacy, and despite the NICE recommendations that we pull back on antidepressant use, continued regulatory approval has allowed prescriptions to just keep going up and up. Of course, this raises uncomfortable questions regarding the precise relationship between the regulatory agencies and the pharmaceutical industry. Do regulatory agencies have an incentive to set the bar so low? While I won't answer that question right now, you can be sure I'll get to it eventually.

5

I was nearing the end of my interview with Irving Kirsch when the window beside us suddenly rattled loudly from a powerful gust of Yorkshire wind. The rain had been falling for a while, forming thick, sinuous rivulets down the windowpanes. I had only just noticed. For over an hour I'd been totally engrossed in Kirsch's story, and neither of us had cared about the deluge outside.

As I turned my eyes back to Irving Kirsch, I now noticed he looked a little tired. It was time to wrap this one up; but first I had just one final question to ask: “How are things going to turn out? I mean, if serious research now shows that antidepressants work little better than sugar pills for most patients, while prescription rates still keep soaring, what's going to alter things? Where do we go from here?”

“To be frank, James, I just don't know,” said Kirsch uneasily. “Back in the old days I used to think I was good at predicting the future, but I've lost my confidence now. I would like to think change is slow, even for the scientific community. But my hope is that change eventually occurs.”

Kirsch looked a little pensive suddenly as he gazed out the window. “Perhaps in the future, twenty years from now, antidepressants will be seen as bloodletting is seen today. That would be really something,” said Kirsch, turning back to me. “But to get to that point, well, it will take time … Yes, it will take lots of time …”

I left Kirsch's house understanding why the war he had triggered in the medical community was still raging so aggressively. There were forces at play that made it impossible for his findings alone to change the current state of affairs. Perhaps science was not in control after all. Perhaps something else, more powerful and less easy to identify, was holding up serious reform. But what could this be?

On my long drive back to London, I told myself that no matter how much more digging it would take, or how many more interviews, I would not stop until I found out.

DUMMY PILLS AND
THE HEALING POWER OF BELIEF

I
n May 1993, a mental disorder that had been in
DSM-III
was repackaged, renamed, and given new life in
DSM-IV
. It was called Premenstrual Dysphoric Disorder and was listed in the
DSM
as a mental disorder.
49
Up to 8 percent of women were said to suffer from the condition. And the condition was apparently nasty. Its main symptoms occurred two weeks before menstruation and included feelings of fatigue, anxiety, emotional instability, disinterest in daily activities, and difficulty in concentrating. In short, Premenstrual Dysphoric Disorder was first presented as if it were an exaggerated form of PMT—premenstrual tension.

By the early 2000s, the number of women in the United States being diagnosed with PMDD was rising exponentially. And there are some obvious reasons for this. The first was that in 1998 the FDA in the United States recognized the condition as an official mental disorder. This freed up doctors to start diagnosing PMDD when previously they had no disorder category to which they could match premenstrual experiences. Second, the pharmaceutical industry now had the green light to market the disorder and its cure. Eli Lilly was the first to step up to the plate by spending $30 million on advertising its chemical cure.

The following advert by the company is illustrative of the type of commercial with which it flooded the airwaves once FDA approval was granted. It shows a woman who has lost her keys growing increasingly frustrated. The voiceover breaks through:

Think it's PMS? It could be PMDD—premenstrual dysphoric disorder. You know, those intense moods and physical symptoms the week before your period. Sound familiar? Call to get free information about PMDD and a treatment your doctor has to relieve its symptoms. Why put up with this another month? [Lilly 2001]
50

Alongside such direct-to-consumer pharmaceutical adverting, Eli Lilly launched a marketing campaign targeting psychiatrists, gynecologists, and mental health providers, who were soon all receiving promotional materials: flyers, free samples, invitations to Lilly talks, and unsolicited visits from pharma reps. As the word spread in the medical community, diagnoses of PMDD quickly soared, and so did the prescriptions.

In the mid-2000s when I met a psychotherapist called John, I was therefore unsurprised to hear he had just recently treated a patient diagnosed with the condition. The patient, Sarah, was an attractive 25-year-old with deep auburn hair and strong, dark brown eyes. She entered his consulting room, lowered herself gently into a chair, and began telling him her story.

“I really am not myself at the moment. I feel so anxious and confused all the time. I just feel, well,
different
. It started about six months ago. I began to get these god-awful cramps before my period. It was like my guts were digesting acid. I also got these piercing headaches and I'd feel emotionally all over the place. I went to my local doctor and he sent me to a gynecologist. The gynecologist said he couldn't find anything physically wrong with me and said I was probably suffering from a psychological disorder I'd never heard of before—Premenstrual Dysphoric Disorder—and he said he could help.”

Sarah then said she had been prescribed a new drug called Sarafem. John asked her what she knew about the drug. “Not much, really.” She shrugged nonchalantly. “Apparently it helps with mood swings and other stuff. I take it every day, and I think it helps with the headaches. I don't know much more than that.”

Let me fill the gaps in Sarah's knowledge.

The pharmaceutical giant Eli Lilly makes Sarafem. Its name is a rework of “seraphim,” a Hebrew word meaning “angel,” a word with obvious
fem
ale overtones.
51
Its packaging also conjures up stereotypical female associations. The pill is encased in a pretty pink-and-lavender shell, and is heralded by Lilly as a wonder cure for this distinctly female premenstrual disorder. So far so good.

Now here comes the interesting bit. What Eli Lilly initially concealed from the millions of women taking the pill is that the pill is actually Prozac. Chemically, Sarafem and Prozac are exactly the same. The only difference between them is that their names and packaging are different. Sarah, like thousands of other women up and down the country, was taking Prozac and didn't know it.
52

2

There are a lot of possible interpretations for why Eli Lilly engaged in what you or I may be tempted to see as corporate deception. The first is that it obviously saved the company a great deal of money. It is cheaper to repackage existing pills than it is to develop new ones. In addition, Eli Lilly's patent protections on Prozac were running out a year after Sarafem would be released, so marketing Prozac under the new trade name would effectively extend patent protections for many more years.
53
Money matters.

But surface appearances also matter. Women, like Sarah, are more likely to feel comfortable consuming pink pills than they are blue pills, because of the associations attached to the different colors. As an article on drug marketing in the
Boston Globe
said at the time, “Drug designers propose colors for a particular medicine and help make sure there are no symbolic mistakes.”
54
An example of a symbolic mistake would be making a pink Viagra, or a menstruation pill that is dark red. Symbolic mistakes occur when the color, shape, or name of a pill does not resonate with its particular consumer. There has to be a positive correspondence between consumer and product to maximize the sales effect—or so the rationale goes.

A final interpretation for Prozac's rebranding was because Prozac is associated primarily with depression, and women labeled with PMDD are not depressed, just as the patient Sarah wasn't. So a new name was required to effectively strip from Prozac associations that were potentially undesirable to this new consumer group. Laura Miller, a marketing associate for Eli Lilly, put it this way:

[Women] wanted a treatment with its own identity. Women do not look at their symptoms as a depression, and PMDD is not depression but a separate clinical entity. Prozac is one of the more famous pharmaceutical trademarks and is closely associated with depression.
55

By rebranding Prozac as Sarafem, Eli Lilly divided the one chemical into two separate pills for two different disorders. One pill continued to be marketed as an antidepressant. The other they marketed as a so-called premenstrual corrective. A new pill was born not because a new chemical had been found, but because a popular brand had been changed.

“Eli Lilly is not alone in rebranding pills,” Nathan Greenslit, a young and dynamic professor at MIT's prestigious Science, Technology, and Society Program, told me. As we exchanged messages about Sarafem online from our respective offices in London and Boston, Greenslit, who has spent years studying the pharmaceutical industry, revealed that in 1997 the FDA approved GlaxoSmithKline's antidepressant Wellbutrin as a smoking cessation pill. But, again, because Wellbutrin was too well known as an antidepressant to be publically accepted as an antismoking pill, Wellbutrin was rebranded as Zyban. GlaxoSmithKline marketed them as separate drugs that targeted separate and discrete disorders: Wellbutrin targeted depression, and Zyban nicotine addiction.

The website for Zyban puts it this way: “Zyban is a nicotine-free pill. Not a patch. Not a gum.” Under the heading “Zyban: Helping Smokers Quit Neurochemically,” the site claims that “while it is unclear exactly how Zyban works, it is thought to act on the part of your brain that is addicted to the ingredients in cigarettes.”
56

“As was the case with Sarafem and Prozac,” Greenslit wrote in an article, “the patient-directed information does not admit that Wellbutrin and Zyban are the same drug.” By giving the old drugs a makeover, they could treat complaints other than those they were designed to treat originally.

What is interesting about these interpretations as to why the rebranding of Prozac occurred is that each is so entirely plausible that it is tempting for you and me to look no further for explanations. The name was changed for reasons of marketing and money—simple as that. But what if it isn't that simple? What if something else is going on here, something far trickier to understand, but something essential to understand to complete the picture? Hold that question in mind.

3

In the last chapter, I discussed the work of Harvard professor Irving Kirsch and how it plunged psychiatry again into crisis by revealing that antidepressants do not work for the reasons people think. He showed they work largely because of their placebo effects and not for the chemical reasons most people believe. But what I did not discuss in that previous chapter was
how
placebos work. How can it be that a sugar pill with no active chemical properties can lighten your mood or decrease your anxiety? The time has come to resolve that mystery.

In the 1980s, the National Institute of Mental Health sponsored a fascinating experiment.
57
It set out to evaluate the effectiveness of antidepressants and psychotherapy in the treatment of depression. The experiment was actually very simple. It asked each patient before treatment began the following question: “What is likely to happen as a result of your treatment?” After the researchers calculated the results, a startling conclusion emerged: the answer the patient gave to this question predicted his or her therapeutic outcome.

In other words, those who expected to feel better improved the most, while those who expected little or no improvement received the least benefit from treatment. Furthermore, this result was the same regardless of whether the patient had been treated with antidepressant medication, psychotherapy, or a placebo. In short, whatever the therapy patients were given, the patients with positive expectations improved most. The conclusion: expectations matter.

But if expectations matter, is there anything that can be done to increase a patient's expectation of recovery and, in turn, his or her therapeutic outcome? The simple answer is yes. To understand what can be done, imagine yourself in the following scenario:

You are sitting in a lecture room listening to a presentation. But you are finding it difficult to concentrate because you have a throbbing headache. Now imagine that the man sitting next to you notices that you are in pain and offers you a small, white pill, quietly telling you the pill will help you feel better. After some deliberation you decide to take the pill (perhaps unwisely) and see what happens. And after a while you notice, disappointingly, that nothing happens at all. So you turn to the man at the end and ask what he gave you. He replies he gave you a sugar pill.

Surely we now have an explanation for why the pill did not work—it was made of sugar. That would be the obvious answer. But the trouble with obvious answers is that they tend to lead us astray. For example, we know from placebo studies that the probable reason the pill did not work will have less to do with its being a sugar pill than with
where
it was given to you and by
whom
. You see, the man next to you was not a medical doctor, and the lecture room is not a hospital, and these contextual factors are significant enough to affect whether the pill will work.

For example, if you were to meet the same man in a hospital and believe him to be a doctor, a curious thing will happen if he gives you the same pill: its effectiveness may increase by up to 40 percent.
58
It is the same man and the same sugar pill, but the effects are now dramatically different. And they are different because the contextual meanings have changed. You are in a hospital and you believe this person to be a doctor, and so you now expect the pill to work. And because you expect the pill to work, it is more likely to do so.

The point of the above illustration is to show that cultural meanings matter. They have the power to increase or decrease, almost subliminally, our expectations for recovery and therefore the extent to which we actually improve.

But how does this insight help us deepen our understanding of why Eli Lilly repackaged Prozac? How could this research be used to explain to Sarah why the pills she was taking were simply a glammed-up version of Prozac? Just recall for a moment that key to the repackaging process was altering the color of the pill. There's our clue. Prozac is green and white, while Sarafem is pink and lavender. So maybe there is something about the color of a pill that impinges not only upon its attractiveness but also upon its effectiveness? Could the very color of a pill help it work?

An early experiment published in the
Lancet
explored this very question.
59
What the group of researchers did was gather up fifty-six medical students and hand each of them a package containing red and blue pills. All the students were told was that one color represented a tranquilizer and the other a stimulant. After taking the pills, the students were then asked which set of pills were the stimulants and which the tranquilizers. The majority concluded that the blue pills were the tranquilizers and the red pills the stimulants. They reached this conclusion because when taking the blue pills they felt far less alert and much drowsier than when taking the red pills. The researchers then told the students that, chemically, the blue and red pills were exactly the same—both sets of pills were made entirely of sugar.

But how could dummy pills yield such different effects? The answer is once again found in recognizing the power of cultural meanings. For the medical students, the colors red and blue each held very different meanings: red means “hot,” “up,” and “danger” (meanings fitting stimulated behavior), while blue means “down,” “calm,” “cool,” and “quiet” (meanings fitting tranquilized behavior). The meanings attached to the different colored pills affected the drug's perceived action and effectiveness.