Manufacturing depression

by Gary Greenberg

  If that seems like a stretch, then you should listen to Peter Kramer.

  One of the strangest things about the antidepressant revolution, and one indication that more is going on here than biochemistry, is that the drugs that started it—the SSRIs, which first appeared in the United States in 1988—are no more effective at treating depression than the generation of drugs invented in the immediate aftermath of Betty Twarog’s discovery. And that’s not very effective. Nearly half the time, the drugs fail to outperform placebos in clinical trials. In real life (which generally lasts longer than a clinical trial and allows for modifications in dosage and brand), they seem to make a positive difference in perhaps 60 percent of the people who take them. You would think that if depression were really biochemical in nature and the drugs were really targeted at the culprit, they’d work better than that. Of course, the first part of that statement remains speculative: despite their best efforts—and notwithstanding what doctors tell their patients when they prescribe them antidepressants—scientists have yet to find a single brain anomaly that is correlated with all cases of depression, let alone one that causes it.

  There are many reasons that antidepressants took hold despite these inconvenient truths, but one of the most important factors in their ascent was Kramer’s Listening to Prozac, which began to fly off of bookstore shelves in the mid-1990s, about the same time that Prozac prescriptions began to fly off of doctors’ pads. Kramer managed to articulate something that all of us—patients, their families and friends, doctors, and drug companies—needed: a credible justification for taking drugs whose principal effect was to make us feel better about ourselves. Listening to Prozac helped make the world safe for antidepressants.

  In his book, Kramer starts out like many of us do about this subject—tentative, searching, ambivalent. As he gathers momentum, however, his case for using the drugs—not only to treat depression, but to “remake the self,” as his subtitle put it—grows stronger, until it turns into a restrained but unmistakable endorsement. And while you have to wonder about that title—Eli Lilly himself couldn’t have asked for better product placement—the fact that permission came not from an ad man but from a neutral expert, a sensitive and honest and articulate eyewitness to the revolution, only strengthened the case for the drugs.

  Listening to Prozac ends with a prophecy. Having spent the better part of three hundred pages worrying over the complexities of using drugs to solve our problems, Kramer speculates that questions like these may already be pointless.

  By now, asking about the virtue of Prozac…may seem like asking whether it was a good thing for Freud to have discovered the unconscious. Once we are aware of the unconscious, once we have witnessed the effect of Prozac, it is impossible to imagine the modern world without them. Like psychoanalysis, Prozac exerts influence not only in its interaction with individual patients, but through its effect on contemporary thought. In time, I suspect we will come to discover that modern psychopharmacology has become, like Freud in his day, a whole climate of opinion under which we conduct our different lives.

  Antidepressants’ most important side effect, Kramer seems to be saying, is the way they change our understanding of ourselves—altering not only our neurochemistry but our sense of its importance. And once that has happened, there’s no more point in inquiring into their virtues than there is in wondering if winter ought to be so cold and snowy. It’s an ironic end to a book that asks about little besides Prozac’s virtue—and which did so much to usher in the climate of opinion under which we think of our unhappiness as a disease.

  Kramer borrowed the phrase climate of opinion from W. H. Auden’s elegy “In Memory of Sigmund Freud.” Freud, Auden wrote, was no longer just a person:

  he quietly surrounds all our habits of growth

  and extends, till the tired in even

  the remotest miserable duchy

  have felt the change in their bones and are cheered

  There was a time, and it wasn’t very long ago, when people didn’t feel in their bones that they “had depression,” when the Centers for Disease Control weren’t calling depression “the common cold of mental illness,” when the World Health Organization wasn’t claiming that depression was “the leading cause of disability…and the 4th leading contributor to the global burden of disease.” It is possible that doctors have gotten better at recognizing depression. It’s possible that contemporary life imposes demands that exceed the neurochemistry bequeathed to us by natural selection. It’s even possible that global warming, widespread warfare, the worldwide economic collapse—that these seemingly irremediable conditions are making us sick with worry. Indeed, all of these explanations for the apparent depression epidemic could be true at the same time, but there is another possible explanation: every new climate of opinion about who we are has its distinctive form of lousy weather. Clinical depression—unhappiness rendered as disease—is ours.

  Climates of opinion don’t descend fully formed from the heavens any more than occupying governments do. If they did, if Betty Twarog’s discovery had simply led to a sudden and cataclysmic change in the way we think of our unhappiness and what to do about it, then the skirmish that broke out in 1995 between David Wong and Arvid Carlsson in the pages of the journal Life Sciences would never have happened. Wong, the Eli Lilly scientist who first formulated Prozac, claimed in passing that his drug was the first SSRI—an assertion to which Carlsson, who won the Nobel Prize for his pioneering work in the neurochemistry of Parkinson’s disease, took exception. Carlsson knew better because he had invented the first SSRI, zimelidine, which the Swedish pharmaceutical company Astra brought to market as an antidepressant named Zelmid in 1982, five years before Prozac. Life Sciences was forced to print a retraction and apology.

  The reason that the editors of Life Sciences didn’t catch Wong’s overreaching—and that you have most likely never heard of Zelmid either—is that Astra never took its drug very seriously, at least not as a big moneymaker. Or so you must conclude from the fact that on the eve of its introduction into the United States, when it began to seem that patients taking Zelmid were prone to contracting the rare neurological disorder Guillain-Barré syndrome, Astra decided not to do the studies necessary to investigate the connection. Instead, it simply pulled the drug from its shelves. The company’s executives just didn’t think there was enough of a market for an antidepressant to make it worth the shareholders’ while. Or to put it another way, they didn’t think there were enough depressed people out there.

  To judge from the industry’s willingness to spend huge amounts of money to minimize their drugs’ association with violence and suicide and other, less dramatic side effects, that’s not a problem anymore.

  The climate changes slowly and imperceptibly, and once it’s settled in, it’s as invisible to us as the sea is to a fish. But if you start to look for it, it’s awfully hard to miss.

  For instance, let’s say you haven’t been able to shake off a setback or a loss, and you find yourself preoccupied and worried, prone to tears, avoiding sex and other pleasures, overeating and undersleeping and just plain not enjoying life as much as you once did. And let’s say you resist this idea that you have an illness, but on the other hand, you’re mighty tired of feeling this way, and one sleepless night cruising the Internet, you end up at depressionisreal.org, a coalition of “seven preeminent medical, advocacy, and civic groups who have joined forces to educate the public about the true nature of depression and how people can live and thrive with this biological disease.” There you can tune into a podcast of the Down & Up Show, which promises to “separate fact from fiction” about depression. You can find out about depression rates in the United States. You can read about depression and women or depression and the Latino community. You can download a mood tracking calendar. You can even take a test that tells you whether or not you have depression. And if it turns out that you do, you can read about resources that you can contact tomorrow, or you can click over and get some
comfort right now from Paul Greengard, a doctor who, as it happens, shared the Nobel Prize with Arvid Carlsson. Dressed in his white lab coat, Greengard gazes reassuringly from beside this message:

  Some say depression is all in your head. Well, that’s right. And wrong. It’s right because depression is in the head, or more precisely, the brain. In fact, we’ve seen how it destroys the connections between brain cells.

  But saying depression is all in your head is also wrong. There’s nothing imaginary about depression. It’s a serious medical condition that affects every aspect of a person’s health.

  Greengard is hardly the only doctor—or even the only Nobel laureate—to deliver this message. It has saturated American popular culture to the point that it is nearly inescapable. And it has done some good. The idea that depression is a treatable medical condition has given people permission to talk to their doctors about suffering for which they might otherwise never seek relief. It has saved lives by preventing suicide, kept families together, helped people to stay productive. And it has had enormous benefits for basic neuroscience: industry interest in finding drugs to treat depression has opened up the coffers to researchers trying to figure out how the brain works.

  Nonetheless, there is indeed something, if not quite imaginary, then certainly invented, about depression. Greengard gives us only two choices: that it is real, which in the current fashion means that it is the result of neurochemical events, or that it is fake, a product of our fickle imaginations or our weak wills. He overlooks a third possibility: that it is made up not by us, but for us, that depression—or at least the version of depression that Greengard is describing—is manufactured.

  Depression is surely an affliction, one that at least in some cases may well have a specific, although still undiscovered, brain pathology—a disease in the usual sense of that word. This is a powerful and compelling idea: if you are unhappy in a certain way, then you are suffering from a brain illness, no different in principle from any other illness. That idea has become part of the way we think about ourselves, part of the incessant chatter of our own minds (or is it our brains?), of the constant self-evaluation by which we mark our lives.

  Am I happy enough? has been a staple of American self-reflection since Thomas Jefferson declared ours the first country on earth dedicated to the pursuit of happiness. Am I not happy enough because I am sick? on the other hand is a question that has just arisen in the last twenty years. This is the sense in which depression has been manufactured—not as an illness, but as an idea about our suffering, its source, and its relief, about who we are that we suffer this way and who we will be when we are cured. Without this idea, the antidepressant market is too small to bother about. With it, the antidepressant market is virtually unlimited.

  My first bout of depression began in 1987, at the same time my first marriage ended. It’s not that I didn’t want the divorce. In fact, it was my idea, an idea I had expressed in a time-honored if ignoble way: by falling in love with another woman. I now think of this transgression as a merciful sort of wickedness, my adultery putting us out of a misery that neither my first wife nor I had the wisdom or courage to end. We were like two comets that had crashed into each other deep in interstellar space. The collision nearly consumed us and left behind nothing but cold and darkness, and, at least for me, a smoldering pile of self-reproach.

  I was thirty years old, a psychotherapist by day, a psychology doctoral student by night, and you would think that at some point—I would nominate the time I found myself on the floor watching dust specks float through sunbeams for hours (because they happened to be in my line of sight, because looking at anything else or closing my eyes and staring at my own black insides would just take too much effort), racked by some unspecifiable pain, like my whole being was a phantom limb, and thinking about that lady in the LifeFone pendant ad, the one who has fallen and can’t get up—you would think that at a point like this it would have occurred to me that I was depressed. Come to think of it, that probably did occur to me. But in 1987, depressed didn’t mean what it has come to mean in the years since. Then it was a convenient description, something to say to a friend or to myself, a shorthand that left the details to the imagination. Now it’s an illness.

  To be fair, depression was already an illness in 1987. It just wasn’t quite so famous as it is now. In fact, it had been an official disease in more or less its current form since the 1980 release of the third edition of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders. The DSM, as it is known in the industry, is a compendium of psychological troubles, sorted into groups (affective disorders, substance use disorders, psychotic disorders) and from there into individual diagnoses (major depressive disorder, alcohol dependence, schizophrenia). And it is indispensable to the business of therapy. Not only does it provide a taxonomy of mental disorders, which in turn gives us therapists a private language in which to talk to one another and a way to feel like we’re part of a guild; it also assigns to each species of anguish a five-digit code. Written on a bill, that magic number unlocks the insurance treasuries, guaranteeing that because we therapists are treating a disease rather than, say, just sitting around and talking to people about what matters to them, we will get paid for our trouble. This is why the most recent edition of the DSM (we’re now on the fourth, with the fifth due in 2012) sits on the shelf of virtually every therapist in the country, including me.

  The DSM is an unparalleled literary achievement. It renders the varieties of our psychospiritual suffering without any comment on where it comes from, what it means, or what ought to be done about it. It reads as if its authors were standing on Mars observing our discontents through a telescope.

  As we will see a bit later, that was exactly the intent of the authors of the third edition, which was a radical departure from the two previous DSMs and the model for subsequent versions. They meant to incite a revolution in psychiatry, a discipline that previously had not hesitated to comment on theoretical (some would say metaphysical) matters such as the origin, nature, and causes of mental anguish. It took a decade or so, and the introduction of a few new drugs, before the revolution was complete, at least with respect to depression. Had my troubles occurred later in that decade, I’d have been much more likely to reach for the LifeFone, to get my diagnosis and the meds to go with it, and to become part of the CDC and WHO statistics.

  I wouldn’t have avoided this path on principle; in fact, as I’ll describe later, drugs (although not the drugs you might expect) did help me finally bring my black dog to heel. But it simply never occurred to me to think of myself as sick. I just figured I’d had a disaster in my life and my unhappiness was the consequence of it, as surely as whacking my thumb with a hammer would have left me injured and in pain and really mad at myself. I worried that I might never get over this, that I would be alone forever, that my finances would never recover, that my divorce was also my initiation into the reality of how hard life really was. I talked about this in therapy, of course, about this and many other subjects. I learned all sorts of things about myself that I didn’t want to know. I marveled at the ability of mercifully long-forgotten chapters of my private history to insinuate themselves into waking life, at the bad faith I could engage in and the pain it could cause myself and others, but my therapist and I never, to my recollection, talked about me as a sick person. Whatever I had seemed like a bad spell that I had to outwait or at least get used to while I did my best to overcome it.

  I did think of depression as a disease; at least I did in my professional life. But I associated that depression with patients like Evelyn. A young woman who was already weeping when I went to fetch her in the waiting room, she told me right off that her life was unmitigated agony. Every success was its own punishment, and her professional achievements, the love of her family, even the sun coming up on this gorgeous spring day only made her feel worse—as she put it, it was as if she were Frankenstein’s monster watching through the window
while the human family lived their happy lives in their warm hut. She said she had called me because she had recently accepted an invitation for a free vacation to Hawaii, and as the date approached she was beside herself with dread. “Because of the expectations to have a good time like everyone else, and the light, that relentless sunshine, which is just going to crush me,” she said. “I know this is as good as it gets, and it’s not good enough for me, which just makes me hate myself more.” She stopped, fixed me in her gaze, and lowered her voice to a near whisper. “I hope the fucking plane crashes.”

  And then there was Ann, the biologist who ended her promising research career to marry a truck driver who beat her and then left her, taking their son with him. She was sure she deserved this and any other failure or indignity that visited her, and her day could be ruined if someone praised her. She was a connoisseur of anguish who had more words for her blue moods than Eskimos allegedly have for snow, who wrung her hands ceaselessly and cried rivers as she talked, but who always seemed surprised when I pointed these things out or expressed concern about them. And not only surprised—she told me frequently that the fact that I paid that kind of attention to her and still seemed to like her reflected poorly on me.

  Or Barbara, who phoned me one night demanding, “You have to tell me why. Give me a reason to go through all this pain.” I told her I knew that she was suffering, that I would listen to her and stand by her and get up in the middle of the night to comfort her, that I would remind her of all the other people who loved her, all the things she still wanted to do, but that beyond that I couldn’t give her what she was asking for. She was dead the next morning, lying in bed next to one of those people who loved her. She had overdosed on her antidepressants.