Manufacturing depression (39 page)

None of this—the lousy sexual performance, the lousy clinical performance, the lousy side-effect profile—is a secret anymore, if it ever was. A search of PubMed, the NIH database of published research, turns up 744 papers on the subject of sexual side effects of antidepressants alone. The data used by the FDA to approve the drugs, including the ones in which the drugs didn’t work, are in the public domain. Even the head of the agency’s division of neuro-pharmacological drugs wondered, when it came time to approve Celexa in 1998, if its clinical trial results showed any “clinical value,” only to be told by a colleague that because
“similar findings
for…other recently approved antidepressants have been considered sufficient,” they had no choice but to go ahead. The agency also knew that reports linking SSRIs to the increased risk of suicide and violent behavior had begun to surface within a year of Prozac’s emergence on the market. Still, by 2006,
antidepressants had become
the most commonly prescribed class of drugs in the United States, at an annual cost of $13.5 billion.

This dramatic success depends on the old tricks—downplaying side effects and overstating efficacy in marketing campaigns directed at prescribers. But it also hinges, at least sometimes, on outright lies. Psychologist Glen Spielmans and his team analyzed a group of ads from leading psychiatric and general medical journals. They discovered that in more than one third of the cases,
the sources cited in the ads failed to verify the claim they were supposed to support. And that’s when the companies bothered to mention a source. Fully half the time, they didn’t even do that—or they cited a source that couldn’t be obtained. When Spielmans asked Wyeth for the data cited in an Effexor ad, the company responded,
“Unfortunately, our internal policies
do not allow for distribution of unpublished data.” As Spielmans pointed out, this is ironic given the tag line of the ad: “See depression, see the data, see a difference.”

Doctors haven’t been keen on investigating how gullible their colleagues are, so it is hard to know just exactly how much of a role these lies play in doctors’ prescribing habits. We do know that
80 percent of “high prescribers”
rated journals as “an important source of information” and that two-thirds of doctors overall are exposed to drug ads on a weekly basis. And we know that an investment of one dollar in professional advertising yields a five-dollar return in sales. Doctors, in other words, seem to respond to ads directed at them by writing more prescriptions.

But even the shrewdest ad will not work if the market doesn’t exist. Before a doctor writes a prescription, especially for a psychotropic drug, he has to believe that the patient is suffering from an illness that can be treated. Which is where the ad men, with a little bit of inadvertent help from the APA and the FDA and the drug czar, found their sweet spot. Because after the long haul through medical school, where doctors learned to think of diseases as targets and drugs as magic bullets, after practicing in a society that expects and even demands results in return for its deference to doctors,
after reading in the
Journal of the American Medical Association
that depression is the second leading cause of disability in the world, but that only 10 percent of the 15 or 20 million citizens who will be depressed in any one year are getting treatment, and that this undertreatment is costing society about $43 billion per year (and that was in 1996, when a billion dollars was real money), after learning, in short, that depression is a public health emergency and
that “safe, effective, and economical treatments are available,” treatments that work as precisely as antibiotics or insulin, that are being talked about by all their colleagues, and taken by their friends and their patients and maybe even themselves—after all that, it’s hard to understand why doctors
wouldn’t
render the diagnosis and reach for the prescription pad. And it’s easy to see why they were
four times more likely
in 2005 to prescribe drugs for the treatment of depression as they had been in 1987. Not because they were in cahoots with the drug companies, not for any other reason than that they wanted their patients to feel better and they really believed they finally had something to offer.

Even without blocking the uptake of a single molecule of serotonin, the drugs begin to work their magic. Doctors—primed by the ads, the detailers, the enthusiastic (if industry-manipulated) articles by their peers—were ready to give their patients Frank Ayd’s pitch: that they had a disease, that it was no different from any other disease (except perhaps for how widespread it is), and that the cure was waiting for them at the pharmacy. They were ready, in other words, to change the setting in which antidepressant use takes place, to name their patients’ pain and create expectation for its cure, to mobilize, whether or not they meant to, the placebo effect.

And it wasn’t only the doctors. The drug industry also had help from writers like Peter Kramer, from a news media more than willing to report breathlessly on the new wonder drug (within a couple of years of its introduction, Prozac was featured on the covers of both
Newsweek
and
Time
), from an FDA hamstrung by its own lax standards, and, perhaps above all else, from millions of satisfied customers.

For four glorious years, Lilly had a monopoly on this emerging market, and the company made the most of it—
the drug’s $1.5 billion in sales
in 1992 accounted for one-quarter of Lilly’s revenue that year. SSRI competition finally emerged, first with Pfizer’s
Zoloft, introduced in 1992, and then, the next year, with Paxil. Some of the competition was fierce. Pfizer, for instance, undercut Prozac’s price by 20 percent and deployed its detailers on 660,000 annual Zoloft visits, with marching orders to harp on Prozac’s side effects—especially anxiety, which Pfizer claimed was less pronounced in Zoloft patients. Ads for Zoloft in professional journals turned
anxiety
into a code word for suicide, reminding doctors of the lawsuits that Lilly had been fending off for years. The success of the whispering campaign quickly showed up on the bottom line: by 1995, Pfizer had captured nearly one-third of the overall antidepressant market, ringing up $900 million in sales. That same year, SmithKline raked in nearly a half-billion dollars from Paxil. Lilly was still on top of the heap at $1.47 billion (capturing nearly 41 percent of the 1995 market), but, as the
Wall Street Journal
reported in mid-1996,
“the king of antidepressants
[was] under attack.”

The news wasn’t really that bad, however. Even if Lilly was losing market share,
its sales were still up by 18 percent
—less than Zoloft’s 38 percent increase and Paxil’s 45, but still enough to account for nearly 30 percent of Lilly’s revenues. Success was breeding success, the market expanding by 33 percent every year. And when the
Journal of the American Medical Association
reported in early 1997 that
still only 10 percent
of the depressed were getting treatment, it seemed that the rising tide was capable of floating as many boats as the drug companies could launch.

Supply was creating demand. It was enough to inspire exuberance in even the most rational executive. But a company selling a product whose patent expires in a few years doesn’t settle for divvying up the market, at least not if it can avoid it—and especially not if the National Depressive and Manic-Depressive Association declares a treatment gap that will only be closed when
“patients [become] informed consumers
and advocates.” Who better than the drug companies to inform them, and what better medium than advertising? Which is why in mid-1997,
Eli Lilly hired the Leo Burnett
Company, one of America’s leading advertising agencies, to launch an ad campaign for Prozac that would skip right over
JAMA
and the
New England Journal of Medicine
and head for
Cosmopolitan
and
Reader’s Digest.
After all, as Willie Sutton might have said, that’s where the consumers were.

According to a Burnett vice president, “This is
one of the most serious assignments
we’ve ever had,” and its mission was clear: to inform readers that, as Mike Grossman, Burnett’s director of public relations, put it,
depression “isn’t just feeling down
. It’s a real illness with real causes.” Lilly spent $22 million in the last six months of 1997—nearly two-thirds of its entire advertising budget for the year—
“assisting people
in their depressed stupor,” as Grossman put it, “to raise their hand for help.”

The first ad
was a three-page spread: a drawing of a rain cloud over the caption “Depression Hurts,” a sun shining on the slogan “Prozac Can Help” (both images were crude, as if drawn by a third-grader), and, on the last page, the fine print about side effects. It turned out that you didn’t need to be in a depressed stupor at all, but merely under the weather, to have the “real illness,” that “doctors believe” may be caused by “an imbalance of serotonin in your body.” The copy under the cloud suggested, “You may have trouble sleeping. Feel unusually sad or irritable. Find it hard to concentrate. Lose your appetite. Lack energy. Or have trouble feeling pleasure.” And when people feel this way, the reader discovered, just before moving to the sunny side, “the medicine doctors now prescribe most often is Prozac.”

One year and $47 million after launching the print campaign,
Lilly and Burnett took Prozac
to television with three sixty-second spots, including “Checklist.” Filmed in black and white, the ad is a montage of suffering and isolation—stills of a woman on a couch, another woman in bed, a man on a pier, another sitting in a restaurant, a woman at her desk, another showering, and finally just a sorrowful face, each person looking as empty and sad and hopeless as Lutherans in an Ingmar Bergman movie. Violins repeat a minor
chord while a woman narrator, sounding not a little depressed herself, ties each image to a target symptom:

Have you stopped doing the things you enjoy?
Are you sleeping too much? Are you sleeping too little? Have you noticed a change in your appetite [at this point the man in the restaurant inexplicably vanishes, as if transfigured]? Is it hard to concentrate? Do you feel sad almost every day? Do you sometimes feel like life [pregnant pause] is not worth living? These can be signs of clinical depression, a real illness with real causes. But there is hope. You
can
get your life back. Treatment that’s worked for millions is available from your doctor.

The commercial provides a toll-free number that you can call for a personal symptoms checklist that will make it “easier to talk with a doctor about how you’re feeling,” and ends with Lilly’s logo and the “Welcome Back” tagline.

Other companies gave Lilly’s campaign the same flattery they had given Prozac: they imitated it. Zoloft and Paxil soon had ads and websites of their own, and by 2000
companies were spending
$128.5 million to advertise their antidepressants to consumers. Laboring under FDA guidelines, which, among other restrictions, required them to disclose side effects and not make claims unsupported by research, the campaigns were barely distinguishable from one another when it came to the information presented. But advertising is much more about presentation than information, and the most creative presentation of the same old facts had to be Zoloft’s.

In 2001,
Pfizer introduced a cartoon character
, a Bizarro version of the smiley face—a round blob that bounces along, sighing and moaning and even ignoring a butterfly as a narrator (male, more chipper than Prozac’s narrator) goes through the usual pitch. The blob ads even featured an animated version of a serotonin synapse; when the Zoloft logo appears at the top of the screen, the synapse becomes a much more lively place, and the narrator says, “When
you know more about what’s wrong, you can help make it right.” He adds that only your doctor can know for sure if you have depression, but he suggests strongly that now that you’re educated, you go and ask.

You have to admire the economy of ads like these. In a one-minute cartoon, they distill a century and a half of medical history into the simple message that if you are suffering, you may very well be sick, that your sickness is internal and biological, that it can be cured with a precision-targeted medicine, and above all else, that anyone can be depressed, that indeed the whole world can be insane. “Depression strikes one in eight,” says the Prozac TV ad. The number is 17 million in the print version, 20 million in the Zoloft ad, and 20 percent of women on Paxil’s website—a whole lot of fellow citizens, in other words, whose suffering was presumably no worse than yours, but who had finally come to understand that their unhappiness, no less than their infections and their high cholesterol, was just another disease and got on the Prozac bandwagon.

Some critics worried that it just wasn’t fair to deploy the techniques of consumer advertising—which, as the
British Medical Journal
put it in an editorial decrying the practice, is
“the science of arresting the human intelligence
long enough to get money from it”—on vulnerable people. The FDA stepped in from time to time—for instance, in 2004, when Wyeth ran a radio spot for Effexor that started out:

Hey you
, listening to the radio…How’re you feeling these days? Okay? Not bad? Come on, is that where you want to be? When was the last time you did something you once looked forward to doing? You know, symptoms of depression could be holding you back.

The FDA faxed a note to Wyeth, warning the company that
“by failing to draw a clear distinction
between major depressive disorder
and normal periodic feelings of low interest or low energy, the advertisement broadens the indication for Effexor XR.” Which was no doubt what Wyeth had in mind. They just weren’t artful enough about it to avoid the FDA’s displeasure. Mostly, however, the drug companies stayed on the right side of the law—not too hard to do when all it took was the careful use of the subjunctive, as in “depression
may
be related to an imbalance of naturally occurring chemicals between nerve cells in the brain” (emphasis added). When a couple of researchers pointed out to the FDA that, according to
Essential Psychopharmacology
, a standard medical textbook,
“there is no clear
and convincing evidence that monoamine deficiency accounts for depression,” the FDA wrote back to say that this was an “interesting issue,” but that “these statements are used in an attempt to describe the putative mechanisms of neurotransmitter action(s) to the fraction of the public that functions at no higher than a 6th grade reading level.” The alleged stupidity of the citizenry, in other words, justified the drug companies’ lying to them.