Manufacturing depression

by Gary Greenberg

  Twenty to forty percent of all men suffer at one time or another from premature ejaculation (PE). (These numbers may be inaccurate; in keeping with the DSM’s requirement that a disorder be a problem for the patient, the benchmark criterion is ejaculation that occurs “on, or shortly after, penetration and before the person wishes it,” so men can have the disease if they think “shortly after” means anytime before they wish it, even if that’s, say, after the four hours promised in the Viagra ads, while men who are just in a hurry to get back to the football game don’t qualify for the diagnosis at all.) As many as 70 percent of people taking SSRIs suffer from sexual dysfunction—which in men often takes the form of delayed ejaculation. Indeed, repeated studies, most of them conducted in European countries, show that the intravaginal ejaculation latency time of men suffering from PE increases significantly when they take SSRIs.

  You don’t have to be a marketing whiz to see the lemonade-out-of-lemons opportunity here. Our pharmacological Calvinism isn’t quite intense enough to justify an ad campaign promising an anti-depressant whose side effects cancel your guilt. (“Makes you feel better, but don’t worry. It will ruin your sex life.”) But the endless desire for sex and the inescapable feeling that it’s never quite good enough offer a chance to turn side effects to advantage by creating a new market for the drug.

  But the fact that the SSRIs do reliably treat an illness, even if it’s not depression, hasn’t yet translated into drug company riches. The reason is obvious. To advertise SSRIs as a cure for PE, the drug companies would have to get an indication from the FDA, and, as one of those European PE researchers pointed out, “focusing on the ejaculation-delaying effects of these drugs would highlight their potent sexual adverse effects and thereby hamper marketing strategies for use of these agents for depressive disorder.” Indeed, currently the industry officially denies, and the FDA officially doesn’t know about, the sexual side effects. According to the package insert for Paxil, for instance, only 1.6 percent of men taking it experience abnormal ejaculation. (That’s probably because clinical trials aren’t exactly designed to elicit accurate information about such intimacies. My Mass General doctors sandwiched their questions about my sex life between items about nausea and muscle cramps. It is as if a person’s sexual performance were no more difficult to talk about with a stranger than his headaches. “Oh, yes, doctor,” we must imagine the subject saying, “I have a sore throat and, now that you mention it, I can’t come. Now, about this backache…”) There’s no particular reason to change this. After all, there is nothing to stop the drug makers from having it both ways—whispering to doctors about antidepressants as an off-label treatment for premature ejaculation while shouting from the rooftops that they don’t interfere with your sex life.

  That may change. Pfizer recently funded a study in which researchers gave Viagra to women suffering from antidepressant-associated sexual dysfunction (look for this one in the DSM-V) to see if it undid the orgasm- and libido-inhibiting effects of Zoloft on women. Seventy-two percent of the women reported improvement, a finding that was trumpeted in press releases that resulted in widespread news coverage. Perhaps when Pfizer finally formulates a combination therapy (Vizoft, anyone?) that promises to enhance both happiness and sexual pleasure—pardon me, to cure major depressive disorder and female sexual dysfunction—those package insert numbers will finally change.

  But I digress. The real point is that to say SSRIs don’t test well is not to say they don’t work. Any clinician can tell you that they do, that he or she has been humbled by how quickly and effectively the drugs improve the lives of some of their patients; and the success of the drugs in the marketplace indicates that the customers are happy.

  The problem with the clinical trials may simply be that they don’t measure what the drugs do, or, to put it another way, that the diagnosis and the treatment aren’t well matched. If researchers want the numbers to break their way more often, then all they need to do is to figure out what the people who actually respond to SSRIs are suffering from, find a way to test for it, and then give it a name.

  Here’s my suggestion: Prozac-deficit disorder.

  Okay, that’s glib and maybe even unfair. But it’s also honest, at least to the extent that it reflects the way doctors actually prescribe the drug. Just ask Richard Kravitz. He’s the physician who led the study in which standardized patients faked depression and then asked for Paxil. I called him to ask about, among other things, what it meant that doctors seemed willing to prescribe the drugs without rendering a diagnosis. “The pursuit of a more precise diagnosis often hinges on the relative risks and benefits of the available treatment,” he told me. “If the treatment is relatively harmless, then sometimes you give empiric therapy a try, as many of these doctors did.” What matters, he added, are results. “People who are unhappy will get better and people with major depression will get better.” Or, as the head of psychiatry at Stanford University once told an interviewer, “for the vast majority of… the walking wounded, the SSRIs are good drugs.” So when someone walks in the doctor’s door, as Kravitz’s accomplices did, bearing the wounds that the doctor has identified as responsive to the drugs, the patient is likely to leave with a prescription.

  This could mean that doctors are lazy or pill-happy. But it could also mean that SSRIs limn a disease, much as Roland Kuhn claimed that imipramine did for vital depression. Is there a homogeneous form of suffering that the drugs relieve? What is the wound that the walking wounded are suffering from?

  This is one of the questions that preoccupy Peter Kramer in Listening to Prozac. He doesn’t approach it head-on, but rather through his careful exploration of the way the drug transformed the lives of his patients. What does it say about the kind of people we are, Kramer wants to know, that a mere pill can do all this?

  In a way, it doesn’t mean anything that you don’t already know, that you can’t figure out if you drink a couple of cups of coffee or shots of whisky, if you smoke a cigarette or a joint or just scarf down a donut and get a sugar rush: there is no such thing as a you without a body. It would be nice if there were, because then things like cancer and death wouldn’t be so scary. (On the other hand, it’s hard to imagine what pleasures like sex and eating would be like, or even how you’d manage them, without a body.) Despite what Daniel Amen and other clinical neuroscientists are saying, no one has figured out how your body, particularly your brain, gives you consciousness—and I doubt anyone will (or maybe I just hope they won’t)—but it’s pretty clear that the old Cartesian idea that the self is like a bird trapped in a cage of bone and blood is untenable. Its modern version—the idea that somewhere in us is an authentic self, waiting to emerge like a sculpture from a slab of marble—is equally unable to withstand the obvious effects of mind-altering drugs, unless you define that self tautologically as whatever is released by the chemical.

  This is why Kramer is sanguine, if reluctantly so, about SSRIs: because there is, in his view, no authentic, nonbodily mind to be spoiled by the drugs. The drugs don’t create a self so much as create the conditions for us to achieve selfhood, whatever it is. He makes this point most clearly when he tells us about Dr. Yang, the healer in Woody Allen’s Alice. He gives the title character an herbal concoction that, Kramer writes, “proves to be a sort of instant super-Prozac”:

  Yang’s herbs allow his patient to experience the world differently—to see husband, lovers, parents, siblings, and children in a new light—and then to bear the possibility of loss inherent in that fresh vision… His drugs only potentiate change; ultimately it is Alice’s quest that transforms.

  The herbs make it possible for Alice to transform herself, but they don’t dictate the nature of that transformation. Similarly, in Kramer’s view, Prozac is just a neutral technology, a dab of lubricant applied to the neural apparatus that allows it to do what it was meant to do in the first place: to produce a competent, effective self.

  Kramer provides plenty of vivid pictures of what happens when
you grease the machinery with Prozac. He tells us about Tess, his first Prozac patient, who once was plagued with “low self-worth, competitiveness, jealousy, poor interpersonal skills, shyness, fear of intimacy” and blossomed all at once into someone

  socially capable, no longer a wallflower but a social butterfly. Where once she had focused on obligations to others, now she was vivacious and fun-loving. Before, she had pined after men; now she dated them, enjoyed them, weighed their faults and virtues. Newly confident, Tess had no need to romanticize or indulge men’s shortcomings.

  Tess joins Sam, the architect who quit his pornography habit; and Julia, the perfectionist who stopped being shrill and short-tempered with her husband and children when she stopped being so demanding of herself; and Lucy, who became less worried about rejection when she stopped looking so deeply (and, Kramer says, accurately) into the nuances of her interactions with her friends, and all the rest of the patients Kramer introduces to illustrate that Prozac’s main effect is to release people from whatever rut they have gotten stuck in. It helps people become the selves they think they should have been all along—outgoing and confident, resilient and optimistic—which is probably why he keeps hearing them say, “On this drug I am myself at last.”

  Being energetic and confident and assertive are surely modern virtues, so it makes sense that people would be delighted to find themselves suddenly in possession of more of them. But there is a virtue beyond those virtues, a peculiarly American aspiration that they also serve: the ability to make ourselves into whatever we want to be, to be limited by no necessity, to seek fulfillment by inventing and reinventing ourselves endlessly. This is the wound that Kramer’s patients are walking around with: the inability to secure that freedom, the disappointment that follows, the loss of the American dream. When Kramer tells us that his patients suffer from a “fixed tragic view,” it’s easy to think the problem is only the pessimism. But it is also, and perhaps more importantly, the “stuckness,” as he calls it. You’re lying on the floor staring at the ceiling and feeling sorry for yourself and the problem isn’t only that you’re distraught; it’s that you can’t get up. You can’t move on from your grief, you can’t get over your unhappy childhood, you can’t let go of your past, you can’t dust yourself off and pick yourself up by your bootstraps, declare your independence and pursue your happiness to the next horizon.

  And it’s not just your biographical self that’s stuck. It’s also your biochemical self, the one whose depression switch is stuck in the on position. There’s even a theory that depression occurs when neurogenesis—the formation of new brain cells, which scientists have discovered does continue throughout our lifetimes—is inhibited, and that SSRIs, in some yet undiscovered way, foster the growth of new brain cells. A depressed brain, in other words, isn’t free to reinvent itself either, at least not until another chemical rides to the rescue, shooting down those growth-impeding molecular villains with its magic bullets. Then you can be yourself at last.

  In this sense, then, mass depression is a disease like neurasthenia. It captures the anxiety and discontents of people living in times of cultural upheaval—in our case, the impending collision between our sense of an ever-opening horizon and the insuperable limits of life on earth, the economic and geopolitical and ecological realities that loom closer every day, the increasing difficulties of pursuing happiness—and turns them into a widespread neurological illness, a whole world gone insane.

  But why bother calling it a disease at all? Why not just say that the drugs help us to be the kind of endlessly flexible and resilient self that our culture has long demanded and leave it at that? For that matter, why not get rid of the middleman—in this case the doctor, with his list of diagnoses and his prescription pad—entirely? Why not just make SSRIs available over the counter?

  I’m almost serious. You will recall that when the FDA came up with the prescription scheme, it simply meant to limit access to drugs whose safe use was too complex to explain in layman’s terms on a label. But, as Richard Kravitz says, most doctors think that the SSRIs are “relatively harmless.” That’s not entirely true—even though the drug companies deny that SSRIs can increase suicidality, the statistics suggest otherwise, and then there are those other, more common side effects. Even so, it’s hard to see how the current model—take this drug and check in with me in a couple of weeks—does much to address whatever dangers the drugs present. More to the point, it’s very hard to use the drugs to harm yourself. That’s more than you can say for aspirin, which will make you bleed to death if you take too much of it, or acetaminophen, which will ruin your liver in a New York minute, or any of a long list of other dangerous over-the-counter drugs. And doctors generally don’t have any particular scientific reason to prescribe you, say, Lexapro rather than Prozac—or, as Kravitz’s study makes clear, to prescribe you anything at all; the signal-to-noise ratio in clinical trials is just too low to make confident predictions about which patient is going to respond to which drug. Neither do doctors adjust your dosage or brand based on lab tests or other findings that only they can gather or interpret. They are providing old-fashioned empiric therapy, which is just a fancy way of saying that they work by trial and error, and when it comes to assessing the results they are at a disadvantage in ascertaining the relevant data: how you are feeling. Surely, that is something about which you are more expert than they.

  But I don’t think for a second that antidepressants are going to go over the counter. To cut doctors out of the loop, which is to say to decouple SSRIs from the disease of depression, would require the drug companies to give up the dispensation that the DSM grants them from the pharmacological Calvinists among us. It would turn the drugs into exactly what the industry doesn’t want them to be: enhancement drugs, mood steroids. It would make them much too close for comfort to alcohol or marijuana or any of the other drugs people commonly take to feel better.

  It’s probably an oversimplification to say that depression as we have come to know it has been manufactured in order to maintain a Maginot line between recreational drugs and antidepressants. On the other hand, you have to marvel at how well the diagnosis protects the pharmaceutical companies from the bad reputations of their illegitimate siblings.

  Consider, for instance, the fact that as many as 50 percent of the patients who stop taking antidepressants experience symptoms including headaches, dizziness, fatigue, sweating, tremors, chills, and nausea, not to mention agitation and anxiety, confusion, and memory problems. (It’s not clear whether this percentage includes the many patients who report simply not liking how they feel without the drugs, the way that their emotional life becomes once again fraught and unpredictable.) These problems are only temporary—they go away when patients start taking the drugs again. This can lead patients to conclude that their depression is indeed a chronic illness, and to resign themselves to remaining on antidepressants for the rest of their lives. The depression doctors are familiar enough with this phenomenon to give it a name: adverse events related to antidepressant discontinuation. But back in your ninth-grade health class, your teacher probably gave a different name to the malaise that occurs when you stop taking a drug and disappears when you start again: withdrawal syndrome, which they list, correctly, as a good reason to be very careful about using mind-altering drugs.

  Your health teacher, or maybe even the cop who led your D.A.R.E. program, probably also told you about drug tolerance, the need to take increasing amounts of a drug in order to get the same effect. As it happens, many antidepressant patients find that the drug’s initially felicitous effects fade after a while, a problem doctors can solve by boosting the dose (or, more often, switching to a different antidepressant). Critics of antidepressants call this “Prozac poop-out,” but mainstream doctors have a much fancier name for it: tachyphylaxis. Some of them have even suggested that it only occurs in people whose improvement was a placebo response in the first place, as if it has to be the patient’s fault when the drug stops working. An
d none of these doctors make the point that your health teacher would have made about a drug that causes tolerance and withdrawal. But then again, they don’t have to. After all, even the D.A.R.E. cop wouldn’t say that a diabetic is addicted to insulin.

  But as dishonest as this evasion-by-renaming is—and it is really dishonest—it does accomplish one good thing. It is hard to imagine that so many people would avail themselves of whatever relief antidepressants offer if the drugs were officially considered addictive. Neither would regulators long tolerate an addictive drug if it weren’t a cure for illness. As long as we live under a pharmacological Calvinist regime, calling depression a disease is perhaps the best way to get drugs into the mouths of the people.

  * * *

  Depression is surely not the only disease that lacks a biochemical known cause; indeed, as scientists grasp more of the complexities of our biochemistry, the magic-bullet model becomes increasingly inadequate to explain illness or to generate cures. But depression is probably the only disease for which doctors insist that they have found the pathogen despite the evidence. The positive results of this bad faith, however, cannot be disputed. Indeed, there is at least one way in which thinking of depression as a disease is helpful. I can imagine less mercenary responses to widespread unhappiness, and better drugs than antidepressants to treat it, but at the same time there’s no use denying that the depression doctors have succeeded in commanding for the unhappy the resources we generally grant to the sick—money for research and treatment, time from doctors and nurses, and, perhaps most important, the kind of sympathy due a victim. In a society that values science over other forms of knowledge, and materialism over other ideologies, a diagnosis is a ticket to collective assets, and the depression doctors have not hesitated to punch it—to their own benefit, of course, but also to their patients’.