Manufacturing depression (38 page)

After correcting this lack of knowledge for 114 pages, Ayd spent his last twenty pages reassuring doctors that they could treat depression.
“Not all depressed people require the services
of a specialist,” he wrote.
“Many melancholics can be cared for
by the family doctor.” Because “no advantage is gained by an intellectual understanding of the psychological aspects of the illness,” a doctor did not need to know how to conduct psychotherapy. Instead, he could just order rest and relaxation, provide support to the family, hospitalize the patient (in a general, not a psychiatric hospital, except in the most severe cases) if necessary, and, of course, prescribe the right drugs—which, according to Ayd, did not include the minor tranquilizers. And when the depression “cleared,” the patient had to be educated about the likelihood of relapse, and reassured that
“treatment can be just as effective
as it was for this attack and that the earlier the treatment is sought…the better.” That’s why he should come in for regular checkups and “at the slightest sign of relapse, treatment should be reinstituted.”

But the doctor’s first duty, Ayd emphasized, was
“to explain to the patient
the nature of his illness in understandable terms.” This was also the tricky part.
“Depressed people are very suggestible,”
he wrote, “and an inept comment can do irreparable harm.” To prevent this, Ayd provided a script for the fledgling doctor to use in breaking the news, one that uses the patient’s suggestibility for better ends:

You have an illness called a depression
. It is very common. Everyone who has it feels just as you do. What is happening is real. It does not mean that you have a serious physical disease
or that you are losing your mind. Your symptoms have a physical basis.

Doctors who give their version of this spiel today probably have never heard of Frank Ayd. Nor have the millions of patients who have listened to it. But his impact, at least to judge from the swollen ranks of the depressed, has been immeasurable.

Neither have most doctors or patients heard of Dan Fellowes, not even by his real name. But it was his idea to send
Recognizing the Depressed Patient
to fifty thousand general practitioners. And, as if playing Gideon with Ayd’s bible of depression wasn’t enough, he also got into the popular music business.
“I found a musicologist
, Leonard Feather, who compiled an album of blues songs,” he said. “It was the most beautiful expression of how life and the problems of life create depression.”

Symposium in Blues,
which was released in 1966, had all the trappings of a commercial entertainment—a major label (RCA), star performers (Louis Armstrong, Ethel Waters, Leadbelly), songs like “I Been Treated Wrong” and “I’m on My Last Go-Round,” and, in case the point wasn’t clear, Feather’s symptom-targeted liner notes (“songs that reflected anxiety and agitation, guilt, hunger or loss of appetite…”). The album wasn’t available in stores, however. Fellowes explained to Martin:

We gave this to doctors
. “Here’s a phonograph record for you.” They took it home…The music didn’t say “Elavil” at all. And there was no intent to give them a lecture. The liner notes talked about the fact that the songs came out during the Depression…It was talking about the psyche of the American public.

The package insert for Elavil was slipped into the dust jacket of
Symposium in Blues,
right next to the record sleeve, and when a doctor opened the album, he was greeted with the Elavil logo, along
with a list of the symptoms of depression. But the album was more than a way to put doctors in the right mood while they read
Recognizing the Depressed Patient.
It was also one of the earliest instances of viral marketing, the kind in which the advertiser lets loose a message in a dim corner of the culture, where it can circumvent whatever immunity we have to the pitchman’s manipulations, attach itself to reputable sources of knowledge, and replicate.

What better host for this kind of virus than the doctor? What better culture than one that has not yet begun to suspect the motives of drug companies and doctors or to worry about their power? Patients surely didn’t know about the record or the book, let alone the phalanx of detailers that eventually included
one sales rep for every eight doctors
in America. They never saw the medical journals, chock full of ads using the latest Madison Avenue techniques to urge doctors to dispense the latest drugs, or attended their industry-funded seminars. A doctor didn’t mention to a patient, as he used his Merck pen to write a prescription for a Merck drug, that he’d learned about the disease at a conference at a luxury hotel in the tropics that was sponsored by Merck, or that the free sample he was handing to you had been given to him by the detailer who took him to lunch the other day. He himself may not have known that the journal article the detailer gave him touting the drug’s virtues was written by a researcher getting paid by its manufacturer, who had been forbidden to publish his results if they didn’t meet the company’s approval.

Despite all these advantages, and despite the best efforts of men like Dan Fellowes, the minor tranquilizers were still beating the antidepressants by a mile. But even before Robert Spitzer and his committee reinvented depression, Elavil and Tofranil and all the rest caught a huge break. In 1968, not long after he arrived in office Richard Nixon made pharmacological Calvinism a matter of national policy. He declared war on drugs, or to be more accurate,
he declared war on the users of some drugs—largely LSD and marijuana, which evidently threatened America’s moral fiber as surely as Communism had when Nixon was a senator and vice president.

As the drug war machine cranked into action, minor tranquilizers got caught in the crossfire. Vice President Spiro Agnew warned publicly about
the dangers of “mood drugs”
in 1970, on which, he said, “over one-half million citizens are now dependent.” A prominent doctor, in a comparison that probably left drug makers reaching for the Valium, said that benzodiazepines were not much different from
“other products which also affect the mind
but which we do not label medicine…for example, alcohol, tobacco, coffee, tea, and marijuana.” The National Institute on Drug Abuse reported in 1976 that Valium was
one of “the most frequently abused drugs
in the United States.” In 1979, Edward Kennedy, chairman of the Senate Subcommittee on Health and Scientific Research, and a man who knew a bit about excess, opened a hearing on the benzodiazepines by declaring that
“these drugs have produced
a nightmare of dependence and addiction…thousands of Americans are hooked and do not know it.”

Whether people were really hooked on Valium remained a matter of debate, but that was never the real problem in the first place. Psychotropic hedonism was.
Addiction
was just a code word for “drugs that you should be afraid of because they make you feel so good.” (Indeed, given the fact that Librium and Valium alone were what
Fortune
called
“the greatest commercial success
in the history of prescription drugs,” it is a safe bet that at least some of the people excoriating them knew this firsthand.) It was not difficult for drug warriors to convince the Drug Enforcement Administration to put minor tranquilizers on its list of controlled substances. Doctors prescribing them would now be under the jurisdiction of the DEA, with all the paperwork that entailed—and all the Dr. Feelgood implications. Patients would have to worry about the stigma of taking a drug that professional scolds were lumping in with marijuana and alcohol. To judge from the falling sales figures—not as
sudden or severe as the decline of the “psychic energizers” in the early 1960s had been, but noticeable by the early 1980s—patients and doctors alike were thinking twice about the benzodiazepines, their market dominance a victim of America’s confusion about drug-induced pleasure.

The drug warriors’ revival of pharmacological Calvinism hit its stride at about the same time that the American Psychiatric Association was resurrecting Kraepelin’s categorical disease entities, which in turn coincided with the FDA’s effort to implement Kefauver-Harris by approving only drugs that were effective with specific diseases. Antidepressants—drugs that didn’t get you high like Valium did, that treated the newly fashioned major depressive disorder, and that allegedly did so by attacking depression at its biochemical source—had hit the trifecta.

Still,
their sales continued to languish
. In 1970, they had constituted only 2 percent of the prescriptions written for psychotropic drugs, and even when the new DSM came out and minor tranquilizers were falling into disfavor, they remained a minor player. One more element was needed, and, unknown to even the most savvy marketers, it was already on the way—and had been since 1968.

That was the year that Arvid Carlsson, the Swedish scientist who had discovered the role of dopamine in Parkinson’s disease and then proved the principle of chemical neurotransmission to the world, began work in earnest on an idea he’d been hatching for a few years. While he believed that Joseph Schildkraut was correct in asserting that depression was a neurotransmitter problem, he thought that Schildkraut had made a mistake by singling out dopamine and norepinephrine as the culprits. Those may have been the chemicals most affected by the tricyclic antidepressants, but, Carlsson pointed out, all the members of that family also blocked serotonin reuptake. And a close look at the statistics showed that the strongly serotonergic drugs were the ones that improved mood—as
opposed to the other items on the HAM-D—most dramatically. A drug that targeted serotonin, Carlsson thought, might be the key to a better antidepressant.

Carlsson’s suggestion that psychopharmacology return to its pioneering discovery—and to the theory that serotonin was the key to mental health and illness—fell on deaf ears until he finally convinced the Swedish firm Astra Pharmaceuticals to finance his research. By 1971, he and his team had come up with zimelidine (Zelmid), the first drug designed specifically to inhibit serotonin reuptake. A year later,
a team at Eli Lilly
synthesized its own serotonin-specific drug: 3-(p-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine.

When the paper announcing Lilly’s drug was published, the company was still calling it LY-110140; it hadn’t bothered to name the compound yet because no one was quite sure of its commercial value. Serotonin, after all, is distributed throughout the body and plays a role in digestion, appetite, sleep, and blood pressure, among other functions, so 110140 might have had many uses. It might even have been used only for research purposes, to assay or manipulate or otherwise investigate serotonin.

Much as Abbott had done with serotonin itself in the early 1950s, the company solicited opinions from leading researchers about the new drug’s possible uses. Arvid Carlsson, who was at one of the meetings, told me that when one scientist suggested that Lilly might try the drug out as an antidepressant, the company representative replied that
this wasn’t in the company’s game plan
.

But in the meantime, Astra, spurred on by Carlsson, was taking zimelidine through clinical trials in Sweden. In 1981, the company received approval to market Zelmid as an antidepressant throughout Europe. The drug did well enough that Merck licensed it from Astra and applied to the FDA for approval in the United States. But in 1983, just as the process was getting under way, trouble arose in Europe:
zimelidine syndrome
, a flu-like condition, and, more ominously, an outbreak of Guillain-Barré syndrome, a sometimes
fatal neurological disorder, among users. Astra withdrew the drug in September 1983, and Merck abandoned its application with the FDA soon after. According to Carlsson, neither company thought the population of depressed people would ever be big enough to justify the expensive research necessary to investigate the link between the drugs and the illnesses.

But the brief success of Zelmid had caught Lilly’s eye. By 1984,
the company was finally interested
enough in 110140’s antidepressant qualities to give it a name—
fluoxetine
—and to conduct and publish research showing that the drug relieved depression as well as the tricyclics, and with fewer side effects. By the end of 1987, the FDA approved the compound, now known as Prozac, as an antidepressant. Zoloft, Pfizer’s entry into the new market, was approved in 1992, and SmithKline Beecham (successor to Smith Kline and French) introduced Paxil a year later.

SmithKline also introduced the abbreviation
SSRI
to the marketplace, underlining the new drugs’ major claim to superiority: that they were selective, targeted precisely at serotonin. Marketers had already jumped on this distinction. The first Prozac ad in
JAMA,
in 1988, touted it as “the first highly specific, highly potent blocker of serotonin uptake,” and throughout the 1990s, the industry put selectivity at the heart of its campaign. Antidepressants, the journal ads proclaimed, were clean drugs, strong and effective drugs, high-tech, can’t-fail magic bullets that destroyed depression without making patients high, without addicting them—and indeed, without causing any collateral damage.

With a come-on like this, it hardly mattered that none of this is exactly true. Not only do the drugs perform poorly in trials, but while they do bind to serotonin receptors at higher rates than they bind to other receptors, and at higher concentrations than the tricyclics do, they by no means bind
only
to serotonin sites. They are active all over the brain, so while they may not cause as many
side effects as the tricyclics, they still cause so much discomfort that there is a cottage industry devoted to reducing nonadherence among SSRI takers. Patients, researchers have found, were reluctant to take psychiatric drugs in the first place, and when they start feeling jittery and agitated, or when they can’t sleep and have upsetting dreams when they do, or when they get constipated or nauseated, or when they hear about the reports linking antidepressants to suicide and violence, and above all else, when they find that
they suddenly can’t reach orgasm
or don’t want sex at all, they often just stop. Indeed,
nearly 70 percent
of people stop taking antidepressants within the first month.