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MANUFACTURING DEPRESSION
A Journey into the Economy of Melancholy
By Gary Greenberg
ON THE SHOW
A story by Wells Tower 05>
ACTURING
DEPRESSION
A journey into the economy of melancholy
By Gary Greenberg
Doctor George Papakostas has some bad I figured anyone paying sufficient attention was
news for me. For the last half hour, he's been bound to show the two symptoms out of the nine
guiding me through a cata- listed in the Diagnostic and
logue of my discontent- StatisticalManual (DSM-N)
the stalled writing projects of the American Psychiatric
and the weedy garden, the Association-sadness, di-
dwindling bank accounts minished pleasure, weight
and the difficulties of par- loss or gain, trouble sleep-
enthood, the wife I see ing, fatigue or malaise, guilt,
mostly in the moments be- diminished concentration,
fore sleep or on our sepa- and recurrent thoughts of
rate ways out the door, the death-that are required for
typical plaint and worry the diagnosis.' To explain
and disappointment of a my certainty and my inter-
middle-aged, middle-class est in his study, I had told
American life, which you Papakostas that these days
wouldn't bore your friends my native pessimism was
with, which you wouldn't feasting on a surfeit of bad
bore yourself with if you news-my country taken
could avoid it and if this over by thugs, the calamity
sweet man with his solicitous tone hadn't asked. of capitalism more apparent every day, environ-
He's been circling numbers and ticking boxes, mental cataclysm edging from the wings to cen-
occasionally writing a word or two in the fat three- ter stage, the brute facts of life brought home by
ring binder on his desk, and now he has stopped the illnesses and deaths of people I love and by my
the interview to flip the pages and add up some own creeping decrepitude. I told him that I had
numbers. His brown eyes go soft behind his glass- more or less resigned myself to my dourness, that
es. He looks apologetic, nearly embarrassed. it struck me as reasonable, realistic even, and no
"I'm sorry, Greg," he says. "I don't think you're more or less mutable than my short stature, my
going to qualify for the study. You just don't
meet the criteria for Minor Depression." I Minor Depression is a provisional diagnosis, listed at the
Even if my confessor had gotten my name right, back of the DSM-IV, where it awaits further study. Re-
I would still be a little humiliated. I had come to search that uses this diagnosis thus has a twofolJ. aim: to
provide another FDA-approved indication for a particular
his office at the Depression Clinical and Research drug and to give Minor Depression medicine's most lucra-
Program of the Massachusetts General Hospital, tive imprimatur-the five-digit code that allows doctors to
insisting that I would qualify. I had told him that bill insurance companies for treatment.
Breathing Head (detail), leaves, photo collage, acrylic, gouache, and resin on
wood panel, by Fred Tomaselli, Courtesy James Cohan Gallery, New York City ESSAY 35
constitutional laziness, my thinning hair, my mod- assistants here-are soon hovering over me in a
est musical talents, the quirks of my personality tiny exam room that contains a metal table and
that drive away some people and attract others. I a scale and a phlebotomist's chair, tweezing ten-
told him that, as a therapist, I lean toward talk tatively through the thatch on my chest and wor-
therapies for psychic distress, but I am not at all rying out loud that they are hurting me. They fi-
opposed to better living through chemistry. If the nally clear the spots for the EKG electrodes and
drugs offered by his clinical trial-Celexa, Forest run the scan. They take my pulse and blood pres-
Laboratories' blockbuster antidepressant, and sure, weigh and measure me, and draw my blood
Saint- john's-wort, an herb with a reputation as a into a vial. Fair-skinned Caitlin is blushing a lit-
tonic for melancholy--did what they promised, I tle as she hands me the brown paper bag with a
might like that, and if! did not, at least I'd know cup for my urine specimen. I can see how cowed
what I was turning down. And, finally, I had told these young women are by this forced intimacy,
him that I was going to write about whatever hap- and I try to tell them they needn't be so shy. But
pened, which meant they know I have just been declared mentally
that either way, I ill, and I wonder if reassurance from the likes of
THIS IS WHERE MEDICINE IS wouldn't come away me just makes things worse.
empty-handed. But I haven't come here to minister to them
INFUSED WITH THE MIRACLES OF Unless I didn't or, for that matter, to maintain my dignity. In this
SCIENCE, AND I'VE COME TO SEE meet the criteria. nondescript office building beside the towers and
But before I can pavilions of Massachusetts General Hospital in
HOW IT'S DONE get too upset, Pa- Boston, these dedicated people do the research
pakostas has more that determines whether drugs work-which is
news. "What you to say, whether drugs will come to market as gov-
have is Major Depression." He looks over the note- ernment-sanctioned cures. In the process, they
book again. "It's mild, but it's not minor. Nope. tum complaint into symptom, symptom into
Definitely major depressive disorder, atypical fea- illness, and illness into diagnosis, the secret
tures, chronic." Which means, he seems pleased to knowledge of what really ails us, what we must
tell me, that I meet the criteria for at least four oth- do to cure it, and who we will be when we get
er studies that Mass General is running. I can take better. This is the heart of the magic factory, the
Celexa or Mirapex or Lexapro or something called place where medicine is infused with the mira-
s-adenosyl-l-methionine. I can climb into an MRI, cles of science, and I've come to see
get hooked up to an EEG, take home a device to how it's done.
monitor my pulse and breathing. I can get paid as
much as $360 for my trouble. I can go back to the
waiting area, read over the consent forms that
I never used the term "magic factory"-you
wouldn't want to seem paranoid in a place like
spell out in great detail--down to the final dispo- this-but I told Papakostas about my suspicions
sition of the two tablespoons of blood that they will of the drug industry and even referred him to
take-what will happen to me, what is expected what I had already written about it. If he caught
of me, what my rights are, how I can bailout if I a whiff of bad faith here, if he thought me a blue-
want to, and then I can make my decision. stocking on an evidence-gathering excursion to
I'm a quick shopper, and when Papakostas re- the porn shop, or if he worried that I would lie to
turns, I have already signed the papers for re- him just to get a story (he knew I was a therapist,
search study l-ROI-MH74085-01Al, agreeing that I was intimately acquainted with that check-
to return to Mass General next week and then list of symptoms), he was too good-natured to
every other week for the next two months, so say SO.3 But then again, he is a doctor and has to
that they can evaluate the alleged antidepres- believe that if depression is the medical illness that
sant properties of omega-3 fatty acids-in other the antidepressant industry is built on-if it is, as
words, fish oil.? the drug company ads say and as doctors tell their
Which is why Julie and Caitlin-tall and at- depressed patients, a chemical problem with a
tractive and polished bright, like all the research chemical solution-then my intentions should-
n't matter. Diseases don't care whether you be-
2 According to the World Health Organization, the coun- lieve in them. What matters is the evidence,
tries with the highest consumption of fish have the lowest
how much insulin is in the blood or how much
rates of depression. And it happens that omega-3s make
cell membranes, such as the receptors in your brain that sugar is in the urine and all the other ways na-
absorb serotonin and other neurotransmitters, more per- ture has of telling you something is wrong.
meable. To a psychiatrist already convinced that depres- But there is no lab to send my bodily fluids to
sion is the result of deficiencies in serotonin transmission,
the significance of this correlation outweighs any of the
other possible explanations for why someone in fish- 3 Or too hard up for subjects. The investigators expect
deprived France might be more prone to depression than that it will take five years to enroll the three hundred sub-
someone in Korea or Japan. jects needed to complete the study.
Millennium Phosphene Bloom, pills, leaves, photo collage, acrylic, and resin on
wood panel, by Fred Tomaselli. Courresy James Cohan Gallery, New York City ESSAY 37
I didn't say this to Papakostas, didn't protest QIDS-SR-comprises sixteen multiple-choice
that my aches and complaints were not really questions. Here is number 11:
Major Depression. Just as well: Item 17 ("In-
sight") on the HAM-D awards two points View of Myself
to anyone who "denies being ill O. I see myself as equally worthwhile and de-
serving as other people
at all."
Airborne Event, mixed media, acrylic, and resin on wood, by Fred Tomaselli.
38 HARPER'S MAGAZINE I MAY 2007 Courtesy James Cohan Gallery, New York City
that uncertainty. I wonder what it means that I and says, "In the past week, Greg, have you
hesitate so long over these questions, whether I had any thoughts that life is not worth living?"
should circle the QIDS item that says, "My It's time for Item 3.
thinking is slowed down." Papakostas is so unfailingly kind-and I want
I haven't finished with the Well-Being him to care, I want him to tell me that I am not
Scale when Papakostas comes to fetch me. I really feckless-that I cannot be mad at him for
tell him I'm confused about a consent form sticking to the script, let alone correct him about
Julie just handed me; she explained that the my name. He's not doing it because he's a bad
one Papakostas and I signed last week was man, or a disingenuous one, or a shill for the drug
"outdated." But, I tell him, this new form companies. On the contrary. He does it because
seems to be for a different study, one that re- he wants to help me, because he thinks I am suf-
quires me to take two different pills at the fering, and because he is a doctor and this is what
same time. He looks perplexed, excuses him- he knows how to do: to find the targets and send
self, and returns with Julie. Together they ex- in the bullets, then
plain that the study I signed up for last week to ask the questions
was full, so they reassigned me. He looks mor- and circle the num- UNDER THE AGREEMENT WE'VE
tified. Julie, who told me she was fresh out of bers and decide if
Amherst, looks worried. They're explaining, those bullets really MADE, THE MEDICINE MUST BE
apologizing, reassuring, as if they were waiters are doing their job.
TREATED WITH THE REVERENCE
in a restaurant who have just delivered the We're not here to
wrong meal to a valued customer. talk about me, at DUE A COMMUNION WAFER
. But we all know what has happened here. least not about the
They have broken the code, the Nuremberg homunculus we call
Code, the one that says that they cannot con- a self. We're trying instead to figureout what's go-
duct experimentation on a human unless the ing on in my head-in the gray, primordial ooze
human in question knows exactly what he's get- where thought and feeling, according
ting himself into, of which it is their responsi- to the latest psychiatric fashion, arise.
bility to inform me. Not only that-and
bad enough, since the U.S. government is pay-
this is
ESSAY 39
feet, and whether either one is more powerful For instance, they can reshape you in a way that
than a placebo. makes you a good fit for the drugs. That's what
This method is known as the "double-blind, these questionnaires, with their peculiar way of
placebo-controlled design," and it provides a way inventorying personhood, do; they alert you to
to deal with something that the drug industry whatit is in yourself that is diseased-casting
would rather forget: that in any given clinical your introspection as "excessive self-criticism,"
trial, especially one for a psychiatric drug, people your suspicions of your own base motives as "low
are very likely to respond to the fact that they are self-esteem," your wish to nap. in the afternoon
being given a pill-any pill, even one containing as "excessive daytime sleepiness," your rooting .
nothing but sugar. Which is why the FDA requires hunger late at night as "increased appetite"-
all candidate drugs to be tested against place- and they prepare you for the cure by letting you
bos-to try to sepa- know how you will feel better.
rate the medicine Just before I got my pills, Papakostas asked me
IN OVER HALF THE TRIALS USED TO from the magic, to how long it had been since I had felt good for any
see what the drug appreciable time. Good? I asked him.
APPROVE THE SIX LEADING ANTI- does when no one is "Symptom-free," he said, as if we had agreed
looking. But, like a that my feelings were symptoms.
DEPRESSANTS, THE DRUGS FAILED
pain-in-the-ass "For how long?"
TO OUTPERFORM THE PLACEBOS brother-in-law, the "Thirty days. Or more. At least a month."
placebo effect keeps I wanted to tell him that I was a writer, that
showing up, curing I counted myself lucky to feel good from the
people at a rate alarming to both regulators and beginning of a sentence to the period. I wanted
industry executives. In fact, in more than half to ask him if he had ever heard of betrayal, of
the clinical trials used to approve the six leading disappointment, of mortality. Instead, I
antidepressants, the drugs failed to outperform laughed-derisively, I suppose (was this the "ir-
the placebos, and when it came time to decide on ritability" of Item 10?)-andsaid I had no idea
Celexa, an FDA bureaucrat wondered on paper what a month of feeling good would feel like:
whether the results were too weak to be clinically Of course, this only confirmed his diagnosis.
significant, only to be reminded that all the oth- But thirty days is ringing in my ears as I head
er antidepressants had been approved on equal- back to my car. I make a sudden decision: to duck
ly weak evidence.e into a restaurant, to order a glass of water with my
Despite the fact that the placebo effect is the meal, to start the trial not tomorrow morning
indirect subject of virtually every clinical trial, but right now. I cannot resist the wish, the temp-
no one really understands how it works. Sci- tation, to lay down my pessimism at this altar, to
ence, designed to break things down to their put myself in the hands of these doctors, to take
particulars, cannot detect something so ineffa- their investigational drug and let them cure
ble, so diffused throughout the encounter be- me of myself. I gulp down my six
tween physician and patient. Until there is golden pills.
money to be made in sugar pills-at which
point the drug companies are sure to investigate
them thoroughlvt-s-about the best we can say is
D rugs do work. By themselves, I mean, even
without the benefit of the placebo effect. Just ask
that the placebo effect has something to do with the tuberculosis patients at Sea View Hospital in
the convergence between the doctor's authority New York who, in 1952, took a derivative of hy-
and the patient's desire to be well. But this rela- drazine, a chemical that Germany used in the
tive ignorance doesn't stop doctors, wittingly or waning days of W orld War II to power its V -2s.
not, from using their power as a healing device. The drug, called Marsilid, worked not only on
their lungs but also on their heads; enough of
6 The advantage of antidepressants over placebos in those them reported feeling euphoric-there was even
trials was an average of two points on the HAM-D, a re- a rumor they were dancing in the wards-that
sult that could be achieved if the patient ate and slept bet- doctors started prescribing it for their melan-
ter. The average improvement in antidepressant clinical tri- cholic patients.
als is just over ten points, which means, according to Irving
Kirsch, a University of Connecticut psychologist, that near- In a society famously ambivalent about pleasure
1y 80 percent of the drug effect is actually a placebo effect. and the use of intoxicants to achieve it, howev-
7 In 2002, researchers observing the EEGs of patients in er, it isn't enough to take drugs to feel better. It's
an antidepressant-versus-placebo trial stumbled on a pat- preferable, especially for a drug company, if you
tern of brain activity common to those subjects who re- have an actual illness to treat. When it was dis-
spond to placebos. Drug companies were very interested covered that Marsilid prevented the brain from
in this discovery, not because it allowed them to study
manufacturing an enzyme that broke down sero-
the placebo effect but because it might allow them to
identify those placebo responders and bounce them out of tonin, an intriguing chemical that had just been
a trial before it starts. found in the brain, scientists had their disease. De-
Breathing Head, leaves, photo collage, acrylic, gouache, and resin on wood
panel, by Fred Tomaselli. Courtesy James Cohan Gallery, New York City ESSAY 43
rived, decontaminated of aspiration and expec- sian is a punishment for something that I've done
tation, is better, truer somehow, than the one (Item 2), and I try joking-"It's an entertaining
we know through our credulous senses and fick- thought, but I haven't had that one"-she seems
le sensibilities. Maybe that's why I don't argue not to notice. When I confess that I'm baffled,
with him when he adds up my numbers and tells even after all this time, by the HAM-D's ques-
me that in the world behind the world, the one tions-"This past week, have you been feeling
in which I am officially depressed, the survey says excessivelyself-critical?"-that require me to parse
I'm getting better. words like "excessively" and "normally" and "es-
Which is news to me. I hadn't been keeping pecially" (something that Papakostas has dealt
track of my HAM-Ds and Q-LES-Qs, but appar- with affably by letting me ramble on until I say
ently my numbers were trending steadily toward something that allowshim to circle a number), she
health. I'm discomfited, disturbed, maybe even a answerswith such crisp condescension-"If there's
little depressed at this, at my apparent inability a comparator implied, it's always to when you're
to know my own inner state-not to mention not depressed"-that I wonder whether I'm the
the possibility that I will have to relinquish my one asking silly questions. Maybe I'm the only
own idea of happiness and settle for person who wonders whether "excessive" means
"symptom-free" living instead. more than I think others do or more than I think
ESSAY 45
I ask her if I was on placebo or drug. She's be- will only stop tormenting us to the extent that we
fuddled for a moment. "I don't think we unblind give it language, with an unconscious populated
the study," she says. She deliberates over my pa- by carbon and hydrogen and nitrogen and oxy-
perwork. "No, not in this one. No unblinding." gen, the basic building blocks of the material
I protest. "I don't get to find out?" It's as if she's world, essential but forever dumb.
never been asked, as if no one in the whole his- Still, I'm not exactly pining for Freud as I
tory of clinical trials had ever wanted to know leave Mass General for the last time. He got too
which side he had been a witness for. much wrong, some of it inexcusably so. Indeed,
"No," she says. "But you had a good re- as I drive through the lunch-hour scurry on the
sponse."lO She's chipper now, like she's trying to hospital-zone streets, the doctors in blue scrubs
convince me that I ought to take my improve- hurrying between buildings, wan patients
ment and go home happy, another satisfied cus- wheeling IV stands down the sidewalks, ambu-
tomer. And really, it doesn't matter. Because lances and private cars delivering a legion of
the point here is not to teach me anything about the sick to this city of hope shimmering in the
myself, or for them to learn anything from me. late summer heat, I am once again struck by
It's not even to prove whether or not omega-Js temptation-to believe, as I hurtle down Stor-
work. It's to strengthen the idea that this is row Drive having these thoughts, passing all
what we are: machines fueled by neurotrans- these other I's having their own thoughts, con-
mitters at the mercy of our own rene- vinced that we are driving ourselves just as sure-
gade molecules. ly as we are driving our cars, that I am wrong