Manufacturing depression (37 page)

Psychologists have had a great deal of fun investigating this phenomenon, and while they disagree about much of it, they have been able to arrive at the not-so-startling conclusion that when it comes to mind-altering drugs, expectation shapes response. People given fake alcohol already know how to be drunk, knowledge they have acquired from experience, perhaps, or from observing others, or from their doctors or teachers or after-school specials—in short, from what Norman Zinberg, a drug researcher of the 1960s and 1970s, called the “setting” of drug use. Setting, Zinberg argued, was only one of three interacting factors that determined the nature of drug experience. The other two were the biochemistry of the drug and the mindset of the user—his psychological makeup, his expectations and desires and motivations for taking the drug in the first place. The effects of drugs, Zinberg said, had to be understood in all three dimensions—drug, set, and setting.

Zinberg cited all kinds of evidence for the importance of this trinity. He found, for instance, that the effects of marijuana had changed over time. Research in the 1950s and 1960s showed that people had to smoke pot two or three times before they could get high on the drug—an effect thought to be the result of some kind of neurochemical process. But by the late 1970s, this was no longer the case.
“As a result of accumulated knowledge
about the effects of marihuana use,” he wrote, “even first-time users are prepared to
experience the high and therefore many have done so.” Pot use had become so widespread that virtually no one, not even a pot virgin, could be naïve to its effects—and this change in setting changed the effect of the drug.

Even with more powerful drugs, Zinberg found, circumstances matter. In the mid-1960s, psychiatric hospitals around the country reported that fully one-third of their admissions were related to the use of LSD and other hallucinogens. A social scientist allied with Zinberg, Howard Becker, argued that while some people were undoubtedly vulnerable to psychotic reactions to the drugs, a much more important factor was the
secondary anxiety
caused by the unfamiliarity of the drugs’ effects, compounded by their sensationalist presentation in mass media, which was in turn reinforced by the dire statistics. An LSD user, especially a novice, confronted with a disturbing hallucination or a raw apprehension of the sublime, might think of Art Linkletter’s famously defenestrated daughter or the tripping students who were said to stare into the sun until they burned out their retinas or the people whose trip never ended. Encountering images like those while on acid can easily lead to the fulfillment of the hysterical prophecy. Becker forecast that as more people used the drugs and didn’t meet tragic ends, as fewer trips ended up in the emergency room, and as this knowledge spread, the actual experience of taking them would change. And the numbers bore him out. By the end of the decade, the bad trips epidemic was over, even though use of the drugs was on the increase. Culture, and not just biochemistry, determined the effects of drug use.

In the course of his career,
Zinberg wrote about
groups whose drug use seemed to prove his theory. He wrote about people who used heroin for years and never got addicted, about rituals, religious and otherwise, that kept drug use from getting out of hand in some communities, about artists who used drugs to enhance their creativity but otherwise avoided them. He concluded that people could be taught to use mind-altering drugs safely and wisely, and that this was a worthwhile thing to learn. But, as he found out when
one of
Harvard’s lawyers objected
to his research on the grounds that a study proving that marijuana was
not
deadly would remove a deterrent to illicit drug use, his research was on a subject about which Americans weren’t exactly rational. The climate of opinion that served as the setting for drug use wasn’t going to change just because it didn’t make any sense.

Zinberg, who died in 1989, never wrote about antidepressants. But there is an obvious connection between his theory and the magic-bullet ideas behind them. After all, if the effects of cannabis and LSD and heroin can change with circumstance, if people can get drunk on the suggestion that they are drinking alcohol, if pain goes away when people think they are taking morphine, then it doesn’t make much sense to talk about psychiatric drugs as compounds that merely straighten out the twisted molecules that give rise to psychic suffering—at least not without giving due consideration to the expectations the doctor hands the patient along with the prescription.

It also doesn’t make sense to think of the placebo effect as a nuisance, an unwanted artifact of credulity that interferes with the hard facts of neurochemistry, or as some vague and general tendency to feel better when a doctor provides a treatment. And it really doesn’t make sense to pretend that what happens between doctor and patient doesn’t matter, that when he asks you about your sleep and your appetite and your sex drive, or about that elusive thirty days, he is only assessing your symptoms, and that when he tells you you are getting better he is only reporting the facts. He’s also loading the dice, helping his drug give you a particular experience by telling you what to look for.

There’s no real scandal here. Doctors have always worked on expectation. And modern doctors have always had help from the drug companies in channeling their patients’ hope into relief: industry-sponsored conferences where logo-emblazoned swag is handed out
like party favors, multipage ads in medical journals, and lunches and golf games in which charming detailers tout the virtues of the latest remedy. Since 1997, when the FDA permitted direct-to-consumer advertising of prescription drugs, however, Pharma has been able to cut out the middleman. Patients, as you’ll see in a moment, now come to doctors with their fires already stoked.

Neither is there anything new, or even disgraceful, in promising the moon to depressed people. Sometimes it doesn’t do any good. Sometimes it just makes them feel more freakish or hopeless. But if you stay realistic and measured, you can often help a person buck up under the onslaught of his own self-reproach. What is new, however, and what has always been changing, is just what moon they can expect to arrive at and which drug promises to take them there.

The first drug touted as an antidepressant was amphetamine.
An ad that ran in a 1945 issue of the
American Journal of Psychiatry
featured a photograph of a man in a business suit, hands on hips, smile on his face, eyes on the horizon as if he is glimpsing the good fortune that awaits him there. Looming behind him, barely distinguished from the background, is a close-up of his face in a different mood—brow furrowed, eyes downcast, mouth curling into a frown. “If the individual is depressed or anhedonic, you can change his attitude by physical means,” the ad copy reads. Doctors, it continues, have known this for at least twenty years, but only in the last decade has the “agent of cure” been available: Benzedrine, “a therapeutic weapon capable of alleviating depression.”

Smith Kline and French, maker of Benzedrine, wasn’t suggesting that doctors give amphetamine to delusionally guilty endogenous depressives or to psychotic manic-depressives—people who would be hospitalized and for whom the cure of choice was still the shock therapies—but to outpatients with what were then thought of as reactive or neurotic depressions. And amphetamine often pulled such patients out of their funks. Its problems—chiefly that it was addictive and its effects unstable—were soon obvious, however,
and it fell into disfavor (until it was resurrected in the 1960s as a cure for attention deficit disorder,
an indication that was worth $1.5 billion
in sales of various stimulants in 2008).

In 1955, Wallace Laboratories, an arm of the company that made Carter’s Little Liver Pills, came up with an alternate treatment for neurotic depression: meprobamate, which the company named Miltown. Full-page ads in medical journals told doctors of the
“outstanding effectiveness…with which Miltown relieves…anxious depression.”
Detailers detailed its virtues. And, perhaps most important, patients loved it. Within a few years of its introduction,
people were “miltowning”
: turning on with a “Miltown cocktail”—a pill washed down with a Bloody Mary—and then tuning in to “Miltown” Berle in such large numbers that drugstores often had to hang out
“No Miltown today”
signs.

By 1965, Wallace had sold 14 billion of its little brain pills to 100 million satisfied customers. The only limit on Miltown’s sales was another group of minor tranquilizers—the
benzodiazepines
, which included Valium and Librium, both invented in the early 1960s by Hoffman–La Roche.
The industry pushed
the minor tranquilizers hard—not only to psychiatrists, but also to general practitioners, the doctors most likely to see the neurotically depressed. In addition to eight-page ads in medical journals, Roche sent out forty different mailings to doctors, along with phonograph records on which doctors testified to the virtues of Librium. Librium’s primary target was anxiety, but it also “could be safely administered in the presence of depression,” the ads said. (And it was, one ad said, perfect for
“when the patient rambles”
—although it is not clear whether the doctor or the patient had to take it for this effect.)
Valium eventually took up more
medical journal advertising pages than any other pharmaceutical drug, and by 1972, it was the most commonly prescribed drug in the world—a position it occupied until the end of the decade. And it wasn’t just Valium. Doctors—mostly family doctors—were writing 90 million minor tranquilizer prescriptions a year.

The minor tranquilizers’ success
wasn’t all hype. In 1972, David Wheatley, one of the earliest antidepressant researchers in the United Kingdom, reported on a series of trials testing antidepressants against minor tranquilizers and concluded that the latter were better at treating neurotic depression—a finding echoed in studies that appeared in the
New England Journal of Medicine
and the
Journal of the American Medical Association.

But the real boon to the drug industry was not so much the drugs themselves as the emergence of a vast new market: people whose suffering wasn’t bad enough to warrant a visit to a psychiatrist’s office but who would confess it to their family doctor and then gladly take Miltown or Valium. Miltown, according to medical historians Christopher Callahan and German Berrios, was
the first “product of the pharmaceutical industry
(rather than academia) [that] responded to consumer demand,” and the success of the minor tranquilizers capitalized on this response. It’s impossible to know how much patients’ newfound willingness to talk about their discontents was due to their knowledge that it might be rewarded with a Miltown buzz, but industry executives didn’t need to consider that. What they knew was that patients were now convinced that the whole world, including them, could be insane, that the insanity could be treated with a minor tranquilizer, and that family doctors, and not psychiatrists, held the keys to the Valium kingdom.

Take some Valium or Miltown (which is still available in a slightly modified formulation called Soma; one can only imagine how Aldous Huxley would feel about that) and, if you’re like most people, you’ll immediately see why they more or less sell themselves: they make you feel pretty darned good. Take some imipramine, on the other hand, and you most likely won’t feel any immediate effects, except maybe some jitteriness or dry mouth. So it’s no wonder that while Valium sales were soaring to the stratosphere, amitriptyline (Elavil), Merck’s entry into the tricyclic antidepressant
market, was down in the dumps—a mere
14 million prescriptions
in 1972, only a 40 percent increase from 1964. Too many doctors, evidently, thought their patients were merely anxious and unhappy, rather than sick with pre-DSM-III depression, the kind that was still considered a psychosis. They were all too willing to prescribe
“penicillin for the blues,”
as one doctor called Valium.

To a marketing executive, the problem was straightforward: doctors weren’t making the connection between the problem and the solution because the problem had not yet been properly named.
“It’s hard to appreciate the difficulty
of getting [across]…the message that we’re all depressed,” Dan Fellowes once told Emily Martin, a medical anthropologist. (Fellowes is the pseudonym Martin gave to the man who oversaw Merck’s Elavil marketing efforts in the 1960s.) But that was his job: to bust antidepressants out of the psychiatric ghetto, he would have to convince family doctors that they didn’t realize how many of their patients didn’t just have the blues, but rather depression, a specific disease for which the specific treatment was not Valium but Elavil.

Fellowes was nothing if not ingenious. One of his first moves was to recruit Frank Ayd, the Baltimore psychiatrist who spearheaded the clinical trials for Elavil. In 1961, Fellowes got Ayd to write
Recognizing the Depressed Patient: With Essentials of Management and Treatment,
a book in which he explained to general practitioners the implications of the
“chemical revolution in psychiatry”
for their practice. Thanks to modern psychopharmacology, Ayd wrote, a referral of a mentally ill patient to a psychiatrist armed with the new drugs was no longer a grim sentence. But even more important, mental illness was increasingly a condition that nonpsychiatrists could treat—if only they recognized it.

Chief among these illnesses was depression. In fact, Ayd wrote,
“depressions are among the most common illnesses
encountered by the general practitioner.” The problem is that the doctor often didn’t know it, didn’t realize that unexplained physical symptoms like constipation and hot flashes, hard-to-pin-down emotional
symptoms like irritability and lack of confidence, and disturbing psychic symptoms like impaired memory and indecisiveness may well add up to depression. Ayd’s symptom list wasn’t as long as George Beard’s was for neurasthenia, but the idea was the same: certain commonly seen, but not obviously related, complaints were the signs of a widespread, although largely unknown, disease.