J 0 A. l\: 1'\ A B () L' R K E 0 \.i THE IN\' E N T I O;\; 0 F II U x 1/\ \: R I lJ I ITS

HARPER'S MAGAZINE/MAY 2007

------------. ------------MANUFACTURING DEPRESSION

A Journey into the Economy of MelancholyBy Gary Greenberg

THE CONTINUATION OF POVERTYRebranding Foreign Aid in Kenya

By Victoria Schlesinger

ON THE SHOWA story by Wells Tower

Also: Lewis H. Lapham and Perry Anderson------------. -------

05>

E S SAY

ACTURINGDEPRESSION

A journey into the economy of melancholyBy Gary Greenberg

Doctor George Papakostas has some badnews for me. For the last half hour, he's beenguiding me through a cata-logue of my discontent-the stalled writing projectsand the weedy garden, thedwindling bank accountsand the difficulties of par-enthood, the wife I seemostly in the moments be-fore sleep or on our sepa-rate ways out the door, thetypical plaint and worryand disappointment of amiddle-aged, middle-classAmerican life, which youwouldn't bore your friendswith, which you wouldn'tbore yourself with if youcould avoid it and if thissweet man with his solicitous tone hadn't asked.He's been circling numbers and ticking boxes,occasionally writing a word or two in the fat three-ring binder on his desk, and now he has stoppedthe interview to flip the pages and add up somenumbers. His brown eyes go soft behind his glass-es. He looks apologetic, nearly embarrassed.

"I'm sorry, Greg," he says. "I don't think you'regoing to qualify for the study. You just don'tmeet the criteria for Minor Depression."

Even ifmy confessor had gotten my name right,I would still be a little humiliated. I had come tohis office at the Depression Clinical and ResearchProgram of the Massachusetts General Hospital,insisting that I would qualify. I had told him that

I figured anyone paying sufficient attention wasbound to show the two symptoms out of the nine

listed in the Diagnostic andStatisticalManual (DSM-N)of the American PsychiatricAssociation-sadness, di-minished pleasure, weightloss or gain, trouble sleep-ing, fatigue or malaise, guilt,diminished concentration,and recurrent thoughts ofdeath-that are required forthe diagnosis.' To explainmy certainty and my inter-est in his study, I had toldPapakostas that these daysmy native pessimism wasfeasting on a surfeit of badnews-my country takenover by thugs, the calamity

of capitalism more apparent every day, environ-mental cataclysm edging from the wings to cen-ter stage, the brute facts of life brought home bythe illnesses and deaths of people I love and by myown creeping decrepitude. I told him that I hadmore or less resigned myself to my dourness, thatit struck me as reasonable, realistic even, and nomore or less mutable than my short stature, my

IMinor Depression is a provisional diagnosis, listed at theback of the DSM-IV, where it awaits further study. Re-search that uses this diagnosis thus has a twofolJ. aim: toprovide another FDA-approved indication for a particulardrug and to give Minor Depression medicine's most lucra-tive imprimatur-the five-digit code that allows doctors tobill insurance companies for treatment.

Gary Greenberg is a psychotherapist and a freelance writer. He is working on a bookabout the misuses of medical diagnoses.

Breathing Head (detail), leaves, photo collage, acrylic, gouache, and resin onwood panel, by Fred Tomaselli, Courtesy James Cohan Gallery, New York City ESSAY 35

constitutional laziness, my thinning hair, my mod-est musical talents, the quirks of my personalitythat drive away some people and attract others. Itold him that, as a therapist, I lean toward talktherapies for psychic distress, but I am not at allopposed to better living through chemistry. If thedrugs offered by his clinical trial-Celexa, ForestLaboratories' blockbuster antidepressant, andSaint- john's-wort, an herb with a reputation as atonic for melancholy--did what they promised, Imight like that, and if! did not, at least I'd knowwhat I was turning down. And, finally, I had toldhim that I was going to write about whatever hap-

pened, which meantthat either way, Iwouldn't come awayempty-handed.

Unless I didn'tmeet the criteria.

But before I canget too upset, Pa-pakostas has morenews. "What you

have is Major Depression." He looks over the note-book again. "It's mild, but it's not minor. Nope.Definitely major depressive disorder, atypical fea-tures, chronic." Which means, he seems pleased totell me, that I meet the criteria for at least four oth-er studies that Mass General is running. I can takeCelexa or Mirapex or Lexapro or something calleds-adenosyl-l-methionine. I can climb into an MRI,get hooked up to an EEG, take home a device tomonitor my pulse and breathing. I can get paid asmuch as $360 for my trouble. I can go back to thewaiting area, read over the consent forms thatspell out in great detail--down to the final dispo-sition of the two tablespoons of blood that they willtake-what will happen to me, what is expectedof me, what my rights are, how I can bailout if Iwant to, and then I can make my decision.

I'm a quick shopper, and when Papakostas re-turns, I have already signed the papers for re-search study l-ROI-MH74085-01Al, agreeingto return to Mass General next week and thenevery other week for the next two months, sothat they can evaluate the alleged antidepres-sant properties of omega-3 fatty acids-in otherwords, fish oil.?

Which is why Julie and Caitlin-tall and at-tractive and polished bright, like all the research

THIS IS WHERE MEDICINE IS

INFUSED WITH THE MIRACLES OF

SCIENCE, AND I'VE COME TO SEE

HOW IT'S DONE

2 According to the World Health Organization, the coun-tries with the highest consumption of fish have the lowestrates of depression. And it happens that omega-3s makecell membranes, such as the receptors in your brain thatabsorb serotonin and other neurotransmitters, more per-meable. To a psychiatrist already convinced that depres-sion is the result of deficiencies in serotonin transmission,the significance of this correlation outweighs any of theother possible explanations for why someone in fish-deprived France might be more prone to depression thansomeone in Korea or Japan.

36 HARPER'S MAGAZINE I MAY 2007

assistants here-are soon hovering over me in atiny exam room that contains a metal table anda scale and a phlebotomist's chair, tweezing ten-tatively through the thatch on my chest and wor-rying out loud that they are hurting me. They fi-nally clear the spots for the EKG electrodes andrun the scan. They take my pulse and blood pres-sure, weigh and measure me, and draw my bloodinto a vial. Fair-skinned Caitlin is blushing a lit-tle as she hands me the brown paper bag with acup for my urine specimen. I can see how cowedthese young women are by this forced intimacy,and I try to tell them they needn't be so shy. Butthey know I have just been declared mentallyill, and I wonder if reassurance from the likes ofme just makes things worse.

But I haven't come here to minister to themor, for that matter, to maintain my dignity. In thisnondescript office building beside the towers andpavilions of Massachusetts General Hospital inBoston, these dedicated people do the researchthat determines whether drugs work-which isto say, whether drugs will come to market as gov-ernment-sanctioned cures. In the process, theytum complaint into symptom, symptom intoillness, and illness into diagnosis, the secretknowledge of what really ails us, what we mustdo to cure it, and who we will be when we getbetter. This is the heart of the magic factory, theplace where medicine is infused with the mira-

cles of science, and I've come to see

I how it's done.

never used the term "magic factory"-youwouldn't want to seem paranoid in a place likethis-but I told Papakostas about my suspicionsof the drug industry and even referred him towhat I had already written about it. If he caughta whiff of bad faith here, if he thought me a blue-stocking on an evidence-gathering excursion tothe porn shop, or if he worried that I would lie tohim just to get a story (he knew I was a therapist,that I was intimately acquainted with that check-list of symptoms), he was too good-natured tosay SO.3 But then again, he is a doctor and has tobelieve that if depression is the medical illness thatthe antidepressant industry is built on-if it is, asthe drug company ads say and as doctors tell theirdepressed patients, a chemical problem with achemical solution-then my intentions should-n't matter. Diseases don't care whether you be-lieve in them. What matters is the evidence,how much insulin is in the blood or how muchsugar is in the urine and all the other ways na-ture has of telling you something is wrong.

But there is no lab to send my bodily fluids to

3 Or too hard up for subjects. The investigators expectthat it will take five years to enroll the three hundred sub-jects needed to complete the study.

in order to assay my level of depression. Instead,there are tests like the Hamilton Depression Rat-ing Scale. The HAM- D was invented in the late1950s by a British doctor, Max Hamilton. He wastrying to find a way to measure the effects of theantidepressants that the drug companies were justbringing to market. To figure out what to test for,he observed his depressed patients and distilledtheir common characteristics into seventeen items,such as insomnia and guilt. Patients could get asmany as four points per item, and a total of eigh-teen of the fifty-two possible points is now con-sidered the threshold for depression. Ten of theseventeen items were about neurovegetative signslike sleep and appetite, th~ kindmost likely to respond to antide-pressants-something Hamiltonknew because he'd worked withthe drugs. Not surprisingly, thisdrug-friendly test quickly becamea favorite of drug companies. Infact, it remains the gatekeeper tothe antidepressant industry, used bythe Food and Drug Administra-tion to evaluate candidate drugs.Because the people from whom

Hamilton derived the items weredetermined already to be sick, theHAM-D cannot be used to diag-nose depression. So psychiatristshave developed the StructuredClinical Interview for DSM-IV(SCID), which is tied to the DSM-IV's catalogue of the 270 afflictionsthat cause people sufficient "psy-chic distress" to be considered di-agnosable mental illnesses (the sec-ond edition of the DSM, publishedin 1968, lists a mere 168 diag-noses). The DSM-IV's fifty-onepossible mood disorders take up 74of its 886 pages, which list criteriaand specifiers that a clinician as-sembles into such diagnoses as Ma-jor Depressive Disorder withMelancholic Features, Chronicwith Seasonal Pattern.There is no magic to the SCID.

To determine whether you meetthe DSM-IV criterion of "depressed mood mostof the day, every day," it asks, "In the last month,has there been a period of time when you werefeeling depressed or down most of the day near-ly every day?" To find out whether you have a "di-minished ability to think or concentrate," it asks,"Did you have trouble thinking or concentrating?"And so on with the lists of symptoms, until, basedon your answers, you get shunted, like coins in asorter, from one chute to another, and you dropinto the drawer with all the other pennies.

I never saw the scoring from my SCID, so I'mnot sure how I ended up with my diagnosis. (I wasrelieved, however, that it would not be enteredinto my medical dossier, where it might wreakhavoc on future attempts to get life or health in-surance or to run for president.) I do know thatI told Papakostas the truth, at least to the ex-tent that I could figure out how to answer hisquestions about my psychic life. And I also knowthat in the course of a quarter-century as a prac-ticing therapist, I have met people who are ham-mered flat, unable to get out of bed or find solacein any quarter, who are nearly insensate to any-thing other than their abject misery, who can

think of little other than dying-who, in short,meet the criteria for Major Depression in my ownprivate DSM. There have been a handful of them,maybe ten or twenty out of the seven hundred orso patients I've seen. Whatever my score on theSCID, it was hard to believe that Papakostas re-ally thought I had Major Depression. I wasn'ttearful with him, and although I whined about thethings that the SCID invited me to whine about,I was alert and smiling, joking, more effusive-perhaps out of nervousness-than I normally am.

Millennium Phosphene Bloom, pills, leaves, photo collage, acrylic, and resin onwood panel, by Fred Tomaselli. Courresy James Cohan Gallery, New York City ESSAY 37

I didn't say this to Papakostas, didn't protestthat my aches and complaints were not reallyMajor Depression. Just as well: Item 17 ("In-sight") on the HAM-D awards two points

to anyone who "denies being ill

J at all."

ulie greets me when I arrive the next week.I'm eavesdropping on the receptionist, who isreassuring someone on the phone that many ofthe doctors at the Depression Clinical and Re-search Program teach at Harvard. I get my

medicine today, assuming that my EKGchecked out, that my blood and urine wereclean of illicit drugs and indication of disease.Julie hands me a clipboard with three question-naires and a pen. The Quick Inventory of De-pressive Symptomotology (Self-Report l-c-the

QIDS-SR-comprises sixteen multiple-choicequestions. Here is number 11:

View of MyselfO. I see myself as equally worthwhile and de-

serving as other people1. I am more self-blaming than usual2. I largely believe that I cause problems

for others3. I think almost constantly about major and

minor defects in myself

The Q-LES-Q-SF, the Quality of Life Enjoy-ment and Satisfaction Questionnaire (ShortForm), wants me to circle the numbers from1 (Very Poor) to 5 (Very Good) that de-scribe how satisfied I've been during thepast week with sixteen aspects of my life,from my economic status to my sex drive, in-terest, and/or performance. And on the RyffWell-Being Scale, I can express-by fillingin the little bubbles, like on the SAT ---oneof six degrees of agreement with fifty-fourstatements about my attitude toward life,such as, "For me, life has been a continuousprocess of learning, changing, and growth,"or, "My daily activities often seem trivialand unimportant."4

The tests in the women's magazines dot-ting the waiting-room tables aren't muchdifferent from these, save for one thing: so-cial scientists have stamped their approvalon the official questionnaires after subject-ing them to various statistical challengesand worrying over such considerations asthe fact that people will answer accordingto how they want to look to the tester. Butaside from a passing frisson over telling Julie,however elliptically, about my very goodsexual performance, I am not thinking aboutimpressing her. I am thinking about howlittle I seem to know of myself. I didn'tknow, for instance, that wondering if "lifeis empty" or "if it's worth living," which I doat least once a week, is, as the QIDS in-sists, a Thought of Suicide or Death. I thinkI march to my own drummer just as muchas the next guy, but when the Well-BeingScale asks me to rate how difficult it is "forme to voice my own opinions on contro-.versial matters," I think of how often I dis-agree with myself over what my opinion is,how the closer I get to fifty the less sure I feelof anything, even of the answer to this ques-tion, and I cannot find a place to bubble in

4 The way that researchers decide whether these tests canaccurately indicate depression is by correlating responses'on them to responses on tests already known to measuredepression-a good idea, unless there is no anchor at theend of the chain, in which case you may well have creat-ed a self-validating semiotic monster,

38 HARPER'S MAGAZINE I MAY 2007Airborne Event, mixed media, acrylic, and resin on wood, by Fred Tomaselli.

Courtesy James Cohan Gallery, New York City

that uncertainty. I wonder what it means that Ihesitate so long over these questions, whether Ishould circle the QIDS item that says, "Mythinking is slowed down."

I haven't finished with the Well-BeingScale when Papakostas comes to fetch me. Itell him I'm confused about a consent formJulie just handed me; she explained that theone Papakostas and I signed last week was"outdated." But, I tell him, this new formseems to be for a different study, one that re-quires me to take two different pills at thesame time. He looks perplexed, excuses him-self, and returns with Julie. Together they ex-plain that the study I signed up for last weekwas full, so they reassigned me. He looks mor-tified. Julie, who told me she was fresh out ofAmherst, looks worried. They're explaining,apologizing, reassuring, as if they were waitersin a restaurant who have just delivered thewrong meal to a valued customer.. But we all know what has happened here.

They have broken the code, the NurembergCode, the one that says that they cannot con-duct experimentation on a human unless thehuman in question knows exactly what he's get-ting himself into, of which it is their responsi-bility to inform me. Not only that-and this isbad enough, since the U.S. government is pay-ing for this research,s and the funding is contin-gent on scrupulous attention to such matters-but for a moment they have laid bare the thingthat all this scrupulous attention to my autono-my is supposed to obscure: that they are using me,that my Well-Being, my Life Satisfaction, myblood, my piss, will all get rendered into raw da-ta for these doctors and their sponsors. Theyhave moved me around like a pork belly, andfor a split second the bald fact of the commercewe are conducting is right in front of our faces.

I reassure them that I am satisfied with theirdisclosures, that I just wanted to make sure wewere all on the same page. Julie leaves theroom with a last apology, and Papakostas handsme my copy of the form, countersigned by him.He opens the binder again and asks me how myweek was. Papakostas has a way of making theHAM-D into a reasonable facsimile of an actu-al conversation. So when he asks me for an ex-ample of what I feel self-critical about (Item 2),I open the spigot a little, telling him I worrythat my insistence on working at my therapypractice part-time, my giving up a plum teach-ing job, my indulgence in writing and otherless savory vices, my seemingly endless desirefor free time-that these reflect a hedonismand irresponsibility that have led me to squan-der my gifts. Papakostas waits a beat, then nods

S About $2.5 million over five years.

and says, "In the past week, Greg, have youhad any thoughts that life is not worth living?"It's time for Item 3.

Papakostas is so unfailingly kind-and I wanthim to care, I want him to tell me that I am notreally feckless-that I cannot be mad at him forsticking to the script, let alone correct him aboutmy name. He's not doing it because he's a badman, or a disingenuous one, or a shill for the drugcompanies. On the contrary. He does it becausehe wants to help me, because he thinks I am suf-fering, and because he is a doctor and this iswhathe knows how to do: to find the targets and sendin the bullets, thento ask the questionsand circle the num-bers and decide ifthose bullets reallyare doing their job.We're not here totalk about me, atleast not about thehomunculus we calla self. We're trying instead to figureout what's go-ing on in my head-in the gray, primordial ooze

where thought and feeling, according

B to the latest psychiatric fashion, arise.

ack on the street, blinking in the noon-day sun, I peek into the brown paper bag theyhave given me. The "study medicine" comesin a pair of plastic bottles stuffed with twoweeks' worth of glistening amber gel caps.They look just like regular prescription drugsbut for the sticker that says, DRUG LIMITED BYFEDERAL LAW TO INVESTIGATIONAL USE. Thatseems a little dramatic for something I can getat any health-food store or by eating howevermuch salmon it would take to provide twograms of omega-3s per day. But under theagreement we've made-that they are doctors,that I am sick, that I must turn myself over tothem so they can cure me-the medicine mustbe treated with the reverence due a commu-nion wafer.

Not that anyone at MassGeneral would sayso.In fact, they've designed this study to minimizethe possibility that something as unscientific asfaith or credulity or the mystifications of powercould be at work here. The trial is a so-calledthree-armed study. I have been randomly as-signed to one of three groups. One group getsplacebos in both bottles. Another group getseicosapentanoic acid and a placebo, and the thirdgroup gets docosahexaenoic acid and a placebo.Only the anonymous pharmacist laboring in thebowels of Mass General, armed with a randomnumber generator and sworn to secrecy, knowswhich group I'm in. The study will then be ableto show which of the two omega-3s has more ef-

UNDER THE AGREEMENT WE'VE

MADE, THE MEDICINE MUST BE

TREATED WITH THE REVERENCE

DUE A COMMUNION WAFER

ESSAY 39

feet, and whether either one is more powerfulthan a placebo.

This method is known as the "double-blind,placebo-controlled design," and it provides a wayto deal with something that the drug industrywould rather forget: that in any given clinicaltrial, especially one for a psychiatric drug, peopleare very likely to respond to the fact that they arebeing given a pill-any pill, even one containingnothing but sugar. Which iswhy the FDA requiresall candidate drugs to be tested against place-

bos-to try to sepa-rate the medicinefrom the magic, tosee what the drugdoes when no one islooking. But, like apain-in-the-assbrother-in-law, theplacebo effect keepsshowing up, curing

people at a rate alarming to both regulators andindustry executives. In fact, in more than halfthe clinical trials used to approve the six leadingantidepressants, the drugs failed to outperformthe placebos, and when it came time to decide onCelexa, an FDA bureaucrat wondered on paperwhether the results were too weak to be clinicallysignificant, only to be reminded that all the oth-er antidepressants had been approved on equal-ly weak evidence.e

Despite the fact that the placebo effect is theindirect subject of virtually every clinical trial,no one really understands how it works. Sci-ence, designed to break things down to theirparticulars, cannot detect something so ineffa-ble, so diffused throughout the encounter be-tween physician and patient. Until there ismoney to be made in sugar pills-at whichpoint the drug companies are sure to investigatethem thoroughlvt-s-about the best we can say isthat the placebo effect has something to do withthe convergence between the doctor's authorityand the patient's desire to be well. But this rela-tive ignorance doesn't stop doctors, wittingly ornot, from using their power as a healing device.

IN OVER HALF THE TRIALS USED TO

APPROVE THE SIX LEADING ANTI-

DEPRESSANTS, THE DRUGS FAILED

TO OUTPERFORM THE PLACEBOS

6 The advantage of antidepressants over placebos in thosetrials was an average of two points on the HAM-D, a re-sult that could be achieved if the patient ate and slept bet-ter. The average improvement in antidepressant clinical tri-als is just over ten points, which means, according to IrvingKirsch, a University of Connecticut psychologist, that near-1y80 percent of the drug effect is actually a placebo effect.7 In 2002, researchers observing the EEGs of patients inan antidepressant-versus-placebo trial stumbled on a pat-tern of brain activity common to those subjects who re-spond to placebos. Drug companies were very interestedin this discovery, not because it allowed them to studythe placebo effect but because it might allow them toidentify those placebo responders and bounce them out ofa trial before it starts.

40 HARPER'S MAGAZINE / MAY 2007

For instance, they can reshape you in a way thatmakes you a good fit for the drugs. That's whatthese questionnaires, with their peculiar way ofinventorying personhood, do; they alert you towhatit is in yourself that is diseased-castingyour introspection as "excessive self-criticism,"your suspicions of your own base motives as "lowself-esteem," your wish to nap. in the afternoonas "excessive daytime sleepiness," your rooting .hunger late at night as "increased appetite"-and they prepare you for the cure by letting youknow how you will feel better.

Just before I got my pills, Papakostas asked mehow long it had been since I had felt good for anyappreciable time. Good? I asked him.

"Symptom-free," he said, as if we had agreedthat my feelings were symptoms.

"For how long?""Thirty days. Or more. At least a month."I wanted to tell him that I was a writer, that

I counted myself lucky to feel good from thebeginning of a sentence to the period. I wantedto ask him if he had ever heard of betrayal, ofdisappointment, of mortality. Instead, Ilaughed-derisively, I suppose (was this the "ir-ritability" of Item 10?)-andsaid I had no ideawhat a month of feeling good would feel like:

Of course, this only confirmed his diagnosis.But thirty days is ringing in my ears as I head

back to my car. I make a sudden decision: to duckinto a restaurant, to order a glass of water with mymeal, to start the trial not tomorrow morningbut right now. I cannot resist the wish, the temp-tation, to lay down my pessimism at this altar, toput myself in the hands of these doctors, to taketheir investigational drug and let them cure

me of myself. I gulp down my six

D golden pills.

rugs do work. By themselves, I mean, evenwithout the benefit of the placebo effect. Just askthe tuberculosis patients at Sea View Hospital inNew York who, in 1952, took a derivative of hy-drazine, a chemical that Germany used in thewaning days of W orld War II to power its V -2s.The drug, called Marsilid, worked not only ontheir lungs but also on their heads; enough ofthem reported feeling euphoric-there was evena rumor they were dancing in the wards-thatdoctors started prescribing it for their melan-cholic patients.

In a society famously ambivalent about pleasureand the use of intoxicants to achieve it, howev-er, it isn't enough to take drugs to feel better. It'spreferable, especially for a drug company, if youhave an actual illness to treat. When it was dis-covered that Marsilid prevented the brain frommanufacturing an enzyme that broke down sero-tonin, an intriguing chemical that had just beenfound in the brain, scientists had their disease. De-

pression, the new theory went, was not a psy-chological or existential condition but a braindisease caused by a "serotonin deficiency" or someother "chemical imbalance." Drug companiesspread this gospel aggressively. In the early 1960s,for example, Merck bought 50,000 copies of Rec-ognizing the Depressed Person, a book by a doctorwho had pioneered the serotonin theory and theuse of drugs to treat it, in order to distribute thebook to doctors who might not yet have heard thatdepression was the disease for which the newdrugs were the cure.But the evidence for the serotonin theory was

circumstantial to begin with, and it has remainedso for the last half-century. Although scientistshave mapped the jungle of nerve fiber through

which serotoninmakes its way frombrain stem tosynapse, analyzingthe biochemistry ofthat journey and in-venting drugs that I

inhibit or encourageit along the way,they have never

proved that a serotonin deficiency actually existsin depressed people or, for that matter, figuredout how much serotonin we ought to have in ourbrains in the first place. Nor have they explainedcertain inconvenient facts: that reserpine, for in-stance, a drug that decreases serotonin concen-trations, also has antidepressant effects, or that somany people fail to respond to antidepressants-which, if antidepressants were really arrows aimedat a molecular bad guy, simply shouldn't be thecase." In the face of these dismal results, manyscientists have begun to move on to theories aboutneurogenesis and cellular damage and other brainevents of which serotonin may be only a marker,the finger pointing to the mood.None of this stops doctors from continuing to

manipulate serotonin in order to relieve depres-sion. The omega-Is I'm taking are thought torender neurons more supple, allowing them tomake the most efficient use of whatever sero-tonin is available. So far, however, the pillsdon't seem to be having an effect. Indeed, as Iend my second week, I notice only one change.When I wake up early in the morning, when Icrave my afternoon nap, when I find myselffrustrated by my shortcomings or deflated by theseeming impossibility of getting done what Iwant to get done, when I read the newspaperand, like Ivan Karamazov with his catalogue of

WHAT WOULD HAPPEN TO THE

CONSUMER ECONOMY IF WE BEGAN

TO BELIEVE THAT ANY AMOUNT OF

HAPPINESS IS ENOUGH?

8 Neither have they shown that in identifying the brainchemistry of a given mood or experience they have foundthe cause rather than the correlates; that is, they couldhave found the ways the brain provides, but doesn't orig-inate, that mood or experience.

42 HARPER'S MAGAZINE / MAY 2007

atrocity, want to return my ticket, when I feelsorry for all of us, I wonder if indeed I've beensuffering from an illness all along.But I am still thinking about those thirty days,

preoccupied with the idea that there are othersright now in the midst of that month of resilienceto setback and hardship who are not simply luck-ier (or, as I think in my self-flattering moments,shallower) but healthier than I, that they havedodged a bullet that has caught me; that I candon some armor and make up for what na-

ture has, so these doctors say, de-~ niedme.

~ he third visit, the first one after I startedthe drugs, is shorter, more perfunctory than thefirst two. Papakostas moves briskly from onequestion to the next and looks at his watch ifwe digress. But the protocol calls for him to askwhether I have any questions. So I tell him Iwasn't sure I had understood him in our lastmeeting. How long was it that he thought Ishould be feeling good?"For at least a month," he saysI ask him why he wanted to know."People, when they're depressed, they get a

sort of recall bias," he says. "They tend to feel thattheir past is all depressed."Which would suggest, I want to point out, that

depression is more like an ideology than an illness,more false consciousness than disease.This isn't the first impertinence I've stifled to-

day. Earlier he asked, "Are you content with theamount of happiness that you get doing thingsthat you like or being with people that you like?""I'm not big on contentment," I said. Is anyone?

I wondered. Is anyone ever convinced that his orher pursuit of happiness has reached its goal?And what would happen to the consumer econ-omy if we began to believe that any amount ofhappiness is enough? "I'm sorry to seem dense,"I explained, "but it's not how I usually thinkabout things."Papakostas was reassuring. "You know, this

question condenses a lot of areas of life into justa number. It doesn't work well," he said. "Somequestions we just don't like."Well, if these are dumb questions, I wanted

to shout, then why are you asking them? Why arewe pretending that these answers mean anything?Indeed, if I'm just the middleman here, the guyyou've got to go through to get to the molecularessence of my troubles, then why ask me anyquestions at all?Later, when he asked how many days there

were in the last week that I had napped for morethan thirty minutes, and I told him four, he said,"See, some of the questions are really nice interms of being objective," before putting me downfor two points on that item.

"I suppose it would be easier if there were bio-chemical markers," I offered. "Otherwise, you'rejust stuck with language."

"Hey, we're psychiatrists," Papakostas said."Language is good."

Now I was really confused. Hadn't we justspent the last half hour circumventing language'sapproximations? If language is good, then whywasn't he taping this visit, taking down my wordsinstead of translating them into the tests' palesimulacrum of language? For the same reason, Isuppose, that he doesn't seem to think that con-sciousness itself, in all its insuperable indetermi-nacy, matters very much, as I discover when wemeet two weeks later. I ask Papakostas about apromising new experimental treat-ment for depression, one that us-es an anesthetic drug called keta-mine. A government psychiatristwas trying to bring ketamine infrom the cold, from the psychi-atric underground where LSD andpsilocybin are used for transfer-mative purposes? and where keta-mine has a reputation for deliver-ing a powerful and salutary (ifterrifying) experience of being dis-embodied and dislocated-not un-like a hear-death encounter. ToPapakostas-who is not familiarwith this unofficial research, dis-credited since the excesses of thesixties grew like an adipose layerover the therapeutic promise ofpsychedelic drugs-I'm explain-ing the idea that a single whackupside the head, one glimpse intothe cosmos and all its glory andindifference, can set you straightfor a long time. I am getting tothe part about how inconvenientthe economics of a one-time-only drug are for an industry ad-dicted to One-A-Days, when heinterrupts me.

"Sort of like ECT," he says, us-ing the new and improved namefor electroshock therapy. 'The wayit's supposed to reset your neuro-transmitters. But we know that theory doesn'twork, because ECT patients relapse."

9 As it happens, these are also drugs that affect serotonin.The concept of "serotonin deficiency" was invented in1954 by two Rockefeller University scientists. In a shortnotice in the back of Science, they noted that LSD,whose profound effects on consciousness were wellknown, contained within itself a copy of the serotoninmolecule, and that serotonin had recently been discoveredin the brain. They speculated that a lack of serotonin,whose role in neurotransmission was still not accepted,must have something to do with mental illness.

"But isn't there a difference between ECTand ketamine?"

"Well, of course ketamine works mostly onglutamate pathways ... "

"No. I mean that you're conscious when youtake ketamine and unconscious when youget ECT."

The distinction seems lost on Papakostas, ormaybe he just doesn't have time for a discussionon the nature of consciousness. Either way, youcannot help but admire the purity of his devotionto the material, the way he has pared down psy-chic life to its bare bones. His is a spare and un-relenting pursuit, and his single-mindedness rightnow seems nearly ascetic.

Papakostas may be circumscribing my subjec-tivity in order to make it work for the drugs, buthe's also renouncing his own subjectivity, puttingaside whatever curiosity he might have aboutthe shape of the self, the objects of consciousness,the raw nature of our encounter, in order to makegood his claim to possess the instruments of sci-ence. Armed with them, he can take my emo-tional measure and report my depression withthe dispassion and confidence of an astronomerreporting the distance to a star. The truth thus de-

Breathing Head, leaves, photo collage, acrylic, gouache, and resin on woodpanel, by Fred Tomaselli. Courtesy James Cohan Gallery, New York City ESSAY 43

rived, decontaminated of aspiration and expec-tation, is better, truer somehow, than the onewe know through our credulous senses and fick-le sensibilities. Maybe that's why I don't arguewith him when he adds up my numbers and tellsme that in the world behind the world, the onein which I am officiallydepressed, the survey saysI'm getting better.

Which is news to me. I hadn't been keepingtrack of my HAM-Ds and Q-LES-Qs, but appar-ently my numbers were trending steadily towardhealth. I'm discomfited, disturbed, maybe even alittle depressed at this, at my apparent inabilityto know my own inner state-not to mentionthe possibility that I will have to relinquish my

own idea of happiness and settle for

I "symptom-free" living instead.

arrive at my next visit resolved to get thedazzleout of my eyes and to make my psychiatristtake account of the seams I think I'm seeing in theMatrix. But as I'm finishing up with the tests onmy clipboard, a petite woman with short hairand large eyescomes into the waiting room. She'snot quite looking at me as she introduces herselfquickly, beckons me to follow her, and, before Ican tell her that there must be some mistake,that I am Dr. Papakostas's patient, she turns herback and briskly leads the way into the warren ofoffices beyond the waiting room.

Papakostas must be away on vacation, I think.It is August, after all. But when we pass his of-fice, there he is at his desk, leaning into hiscomputer screen. He doesn't see me. I imaginethat he has tired of my questions or that his col-leagues have caught wind of our extracurriculardiscussions, all that language, decided it's timeto remind me who is asking the questions aroundhere, and pulled him off the case. Whatever theexplanation, it is hard not to take this person-ally-which, of course, is exactly how a de-pressed person, whose disease makes him "re-jection-sensitive," would take it.

In fact, I can't seem to escape the gravitation-al field of my diagnosis today. When I tell the newpsychiatrist I didn't catch her name, she repeatsit carefully and slowly,as if to account for my"psychic retardation." When I explain why I amgoing to record our session (she asked, somethingPapakostas never did), she says,"Oh ... in-ter-est-ing," filling the spaces between syllables withprofessional smarm. I suspect that she's runningthe numbers in her head and wondering whetherthis will be the "difficult" interview that's worththree points on Item 8.

If the purpose of the switch was to make thingsmore businesslike, then Christina Dording wasthe perfect choice. She iscold and unflappable, herlineswell rehearsed, her inflectedconcern perfectlypitched. When she asks me if I think my depres-

44 HARPER'S MAGAZINE / MAY 2007

sian is a punishment for something that I've done(Item 2), and I try joking-"It's an entertainingthought, but I haven't had that one"-she seemsnot to notice. When I confess that I'm baffled,even after all this time, by the HAM-D's ques-tions-"This past week, have you been feelingexcessivelyself-critical?"-that require me to parsewords like "excessively" and "normally" and "es-pecially" (something that Papakostas has dealtwith affably by letting me ramble on until I saysomething that allowshim to circle a number), sheanswerswith such crisp condescension-"If there'sa comparator implied, it's always to when you'renot depressed"-that I wonder whether I'm theone asking silly questions. Maybe I'm the onlyperson who wonders whether "excessive" meansmore than I think others do or more than I thinkI ought to. Maybe her answer isn't as circular asit sounds, maybe it means more than saying it's aproblem when it's a problem and not when it's not,maybe it isn't yet another denial of the basic as-sumption here-that they are the experts aboutmy mental health, that depression isn't some-thing I'm equipped to detect in myself, because ifI was, I'd be in the other study, the one for the Mi-nor Depression I thought I had in the first place.Or maybe all these maybes, and my resulting in-ability just to blurt out a yes or a no, are just an-other example of my "excessive self-criticism."

Dr. Dording and I are not off to a good start.Which makes it a little easier to interrupt theinterview to ask her whether she really thinksself-criticism is pathological.

"Pathological?" she asks, as if such a thing hadnever occurred to her. "I don't know if I'd callit pathological."

"Symptomatic, then," I offer."Well, it's certainly not optimal.""Optimal," I say, deploying the therapist's

repeat-and-pause tactic, hoping she'll tell me ex-actly how much self-criticism is optimal, andhow she knows.

"Certainly not optimal." She doesher own pause."But being self-critical is something that helps

people succeed, isn't it?""Sometimes yes, sometimes no. I don't think

being excessively self-critical is ever a great thing.No." She starts turning pages again, resumesthe interview.

But I don't want to let it drop. I've come topull back the curtain, and, the numbers aside, Iwant to know, colleague-to-colleague, just be-tween us pros, do I really seem depressed to her?Majorly depressed? I ask her to tell me what shethinks the difference is between Major Depres-sion and Dysthymia, a DSM-IV mood disorderthat, if I have to be diagnosed, comes closest tocapturing my melancholy.

"You're getting into close quarters here,"she says.

In another world, one in which psychiatristsac-tually liked language, we might explore this slip-for she really means to say that I'm getting intofine diagnostic distinctions here-and its reve-lation of discomfort at my intrusion into her pro-fessional space. But she seems unaware of what shehas just said as she explains: "Dysthymia is morelow-level chronic. Minor Depression mayor maynot be long term, but it typically has less criteriathan Major Depression."

And before I can ask her how any of this com-pares with what she actually sees, she closes thenotebook and walks me' out.

George Papakostas is a few paces in front of meas I round the corner of the reception desk. He'sheaded for the men's room. I decide to spare himstrained pleasantries at adjoining urinals. But Idawdle to the elevator, and he shows up just asit arrives. We ride down and walk out of thebuilding together. I tell him how fascinating Ifind this process, and how many questions I stillhave. I'm working toward asking him if we can ex-tend our next meeting somehow, maybe go out forlunch or something, so that I can debrief him. Buthe tells me he is going to Greece to visit his ail-ing father, and he won't be back in time. Weshake hands goodbye.

I imagine that he is relieved to be done with me.I know how this looks to him, the patient chal-lenging the boundaries of the professional rela-tionship, the What About Bob? nightmare. Or Ithink I do. Maybe I don't know anything aboutthis. Maybe what he really sees as we stand on thethreshold of his concrete fortress is a conversationorchestrated by ion channels and neural path-ways and axonal projections, two people deep inthe grips of their chemicals, one of them stillclinging (because of those chemicals, no doubt)to his old-fashioned idea that he is more than thesum of his electro molecular outputs, that a con-versation like this one, not to mention recalcitrant

unhappiness, might be complex and

I mysterious and meaningful.

am already deflated when I arrive for my lastinterview. Of course, there's no place in theHAM-D to express this, to talk about the im-measurable loss that I think we all suffer as scienceturns to scientism, as bright and ambitious peopledevote their lives to erasing selfhood in order tocure it of its discontents. The HAM- D questions,Dording's unconvincing solicitude, the banalityof this exercise, the tyranny of the brain-they allseem as unassailable, solid, and impenetrable asthe office building itself. I'm downright unpleas-ant when Dording asks me if I've been feelingguilty or self-critical. "A constant feature of mylife," I say. She ignores me.

But then she does something strange. She skipsthe Insight item, the one where she's supposed to

ask whether I think I'm suffering from an illnessand to give me points if I don't think I am. I askher why. "You typically don't ask," she replies. "It'satypical that a person is something other than azero. Clearly psychotic people could have a two.There are occasions when you can get a one, likeif a person thinks their lack of interest or energydoesn't have anything to do with being depressed.But typically people who are in here are a zero."

"So you would have to be either psychotic orbelieve that your symptoms are the result of someother conditions?"

"Yeah.""As opposed to just saying, 'Well, you know,

this is just how I am.!""That's a good question. I think that an answer

like that would require an explanation. You wouldneed to talk a littlemore about an an-swer like that." AndI'm thinking that weshould have this dis-cussion, right now,because I am thatpatient, and I don'tthink I'm psychotic.

But that isn't go-ing to happen. Instead, Dording is going to giveme a physical. She goes to find out if the examroom is available, returns to tell me that it is not,that I can wait or do it on my next visit.

"Next visit?" I ask. According to the proto-col, this is my last.

"You're not coming in for the follow-up?" Shelooks as surprised as I am, as if no one would passup that opportunity. I ask whether it would beany different from what we've been doing. Itwouldn't, she says. So I tell her I'll skip thefollow-up and wait for my exam.

Julie is also gone for vacation, so Caitlin takesmy vitals and draws my blood. Then Dr. Dordingcomes in. She taps my knees, looks in my mouth,listens to my heart and lungs. When she asks meto follow her finger with my eyes, she puts herhand on my bare knee. The touch of her finger-tips is firm and cool and impersonal, my kneejust a prop to hold her up.

She repeats her offer of follow-up, then elab-orates on something she mentioned at the end ofour interview. "Give me one second here," shehad said as she flipped the pages of my binder."Look at your scores. Nice response." Now shesays, in case I didn't get it the first time, "I thinkyou've done very well, you're much improved."She doesn't ask whether I agree, nor does sheexplain why if I'm better I would need follow-up,why I would need to do more than buy some fishoil at the Whole Foods next door.

If, that is, I have been taking fish oil for the lasteight weeks.

NUMBERS ASIDE, I WANT TO

KNOW, JUST BETWEEN US PROS, DO I

REALLY SEEM DEPRESSED TO HER?

MAlORLY DEPRESSED?

ESSAY 45

I ask her if I was on placebo or drug. She's be-fuddled for a moment. "I don't think we unblindthe study," she says. She deliberates over my pa-perwork. "No, not in this one. No unblinding."

I protest. "I don't get to find out?" It's as if she'snever been asked, as if no one in the whole his-tory of clinical trials had ever wanted to knowwhich side he had been a witness for.

"No," she says. "But you had a good re-sponse."lO She's chipper now, like she's trying toconvince me that I ought to take my improve-ment and go home happy, another satisfied cus-tomer. And really, it doesn't matter. Becausethe point here is not to teach me anything aboutmyself, or for them to learn anything from me.It's not even to prove whether or not omega-Jswork. It's to strengthen the idea that this iswhat we are: machines fueled by neurotrans-

mitters at the mercy of our own rene-

O gade molecules.

nee upon a time, the scientific explanationfor depression sounded something like this:

Ifone listenspatiently to amelancholiac'smany andvariousself-accusations,one cannot in the end avoidthe impression that often the most violent of themarehardly at all applicableto the patient himself,butthat wirh insignificant modifications they do fitsomeoneelse,someonewhom the patient loves,haslovedor shouldlove.... Sowefindthe keyto the clin-ical picture: weperceive that the self-reproachesarereproaches against a loved object which have beenshifted awayfrom it on to the patient's ego.

For a modernist like Freud, who wrote Mourningand Melancholia in 1917, depression was embed-ded in history, personal and cultural, and untan-gling that history, rescuing it from the oblivionof the unconscious by turning it into a coherentstory, was the key to a cure. A fascinating andtragic notion-that we carry within us an otherwhom we can never fully know, but whom wemust try to know-is headed for the dustbin ofhistory. Freud, with his extravagant hermeneutics,his because- I-said-so epistemology, his unfalsifi-able claims-not to mention the sheer ineffi-ciency of psychoanalysis-has given way to theDordings and Papakostases of the world, withtheir inventories and brain scans and pills. Theyhave replaced Freud's unconscious, the reposi-tory of that which is too much to bear and which

10 All of which raises the question of how the doctorsknow what kind of follow-up to provide, whether to givea drug or not. Later, the lead investigator on the study,David Mischoulon, told me that they "take their bestguess" about whether the subject was on drug or placeb9.The reason for not disclosingmy experimental condition,he explained, was so that doctors wouldn't detect a pat-tern in the responses and thus "break the blind." Headded that I could indeed find out when the study is com-pleted--about five years from now, he estimated.

46 HARPER'S MAGAZINE / MAY 2007

will only stop tormenting us to the extent that wegive it language, with an unconscious populatedby carbon and hydrogen and nitrogen and oxy-gen, the basic building blocks of the materialworld, essential but forever dumb.

Still, I'm not exactly pining for Freud as Ileave Mass General for the last time. He got toomuch wrong, some of it inexcusably so. Indeed,as I drive through the lunch-hour scurry on thehospital-zone streets, the doctors in blue scrubshurrying between buildings, wan patientswheeling IV stands down the sidewalks, ambu-lances and private cars delivering a legion ofthe sick to this city of hope shimmering in thelate summer heat, I am once again struck bytemptation-to believe, as I hurtle down Stor-row Drive having these thoughts, passing allthese other I's having their own thoughts, con-vinced that we are driving ourselves just as sure-ly as we are driving our cars, that I am wrongabout who I am, that we are all wrong. Thatscientists peering into the darkness in our skullswill eventually illuminate it entirely and showus that such thoughts and the conviction withwhich they are held are only accidental: span-drels of our cerebral architecture that can be re-arranged with surgical precision. And just as weonce were playthings for the gods or sinnerspoised over a fiery pit or enlightened rational-ists cogitating our way to the truth of ourselves,we will become the people who needn't takeourselves too seriously, who will stop mistakingthe vicissitudes of personal history for the va-garies of personal biochemistry, who will giveup the ghost for the machine.

Because irresistible ideas about who we areonly come along every so often, and here atMass General they've gotten hold of a big one.They have figured out how to use the giganticapparatus of modern medicine to restore ourhope: by unburdening us of self-contradictionand uncertainty, by replacing pessimism with"optimization," by inventing us as the peoplewho seek Life Enjoyment and Satisfaction, whowill buy from the pharmacy what we need toforge ahead toward W ell- Being unhindered byDepressive Symptomatology, to pursue antide-pression if not happiness. Who can resist thisidea that our unhappiness is a deficiency that isin us but not of us, that it is visited upon us bydumb luck, that it can be sent packing with adab of lubricant applied to a cell membrane?

The epiphany makes me wonder whether I'vebeen unduly churlish to Christina Dording;maybe I should take her word for it, accept thatI am better now, and thank her. But remorse lastsonly as long as it takes to get the results from thelab to which, out of curiosity, I sent my pills.There wasn't a drop of fish oil among them; I wason the placebo. -