Manufacturing depression

by Gary Greenberg

  But simplicity can be a good thing too, at least once in a while, and here’s the simplest thing I’m going to tell you, the closest to advice I’m going to come.

  Whatever else you do, don’t let the depression doctors make you sick.

  This is harder to do than it sounds. Because you have to grant the brilliance, the irresistible narrative power of the story they have manufactured. The depression doctors have found a middle way between Job and Eliphaz, one that can be truly comforting: that your depression is a flaw, in you but not of you, that causes you to see the world as darker and meaner than it really is and that can be corrected with a quick trip to the drugstore. And especially as we move into a time of deep uncertainty, economic and otherwise, and the opportunities to feel worried and disconsolate and even despairing increase, as more and more patients show up in doctors’ offices sleepless and upset and agitated and worried and wondering whether life is worth the candle now that their jobs and their 401(k)s have disappeared, or now that they have to tell their kids that they’re losing their house or moving from their hometown because there just aren’t any jobs left, or now that they realize they may never be able to retire—as, in short, more and more of us meet the criteria, doctors are going to be dispensing the diagnosis even more often than they already are.

  If you’re going to resist this prescription, which has the signal virtue of leaving the world intact and giving you the opportunity to live in it more comfortably, you will have to remember that the depression doctors exact a price for their diagnosis. They want to tell you who you are. They want you to see yourself as the kind of being whose unhappiness is a sign that you need to buy their services. And you’re going to have to remember that hidden in the diagnosis, and in the vast assumptions about humankind behind it, is a whole history of accident and misunderstanding and overreaching, of unwarranted leaps of logic and wishful thinking and the misapplication of scientific rhetoric, of bad faith and greed. They don’t teach this history in medical school, and few doctors have the time or patience or inclination to learn it. So now that you know more than they do, you’re going to have to consider the possibility that even if you take their drugs and feel better, that doesn’t mean you were sick in the first place. And then you are going to need new ways to understand your discontents.

  I’m not going to tell you what those new ways should be. You’d want to be pretty sure of yourself before you try to convince people you’ve never met that you know what causes them to feel a certain way and what they ought to do about it. And the simple fact is I’ve been working with depressed people and I’ve been depressed on and off myself for a quarter century, and I’ve spent the last couple of years writing a book on the subject. And I still don’t know the answer to those questions.

  Because you could write that book, as I have, and then as your reward you could take yourself to a tiny cabin on an island without either cars or roads (and whose sole concrete sidewalk features speed bumps), and you could be awakened at three in the morning by a sudden shift of the wind, by palm leaves slapping the sides of your cabin and an occasional quarter-sized raindrop plunking its tin roof. You could sit up in bed and look out your window at an orange crescent moon on the eastern horizon, lighting a faint path across the sea, and before you could congratulate yourself for having found such a place, before you could even begin to try to tame this riot of beauty with words, you could become aware of something else: your pounding heart, your stomach hollow with nausea, the sudden dead certainty that something is wrong and will never be put right. This is all so disappointingly familiar, and because you don’t want to be depressed on your vacation, you hope that this ill tiding blown across a vast ocean from an unseen continent is bound for some other destination.

  The feeling has descended like the weather, unbidden and dismal and blacker than the night, and you can’t help but think that this is a random event, a synaptic thunderstorm signifying nothing that you don’t already know or need to be reminded of: that the flesh is infinitely vulnerable, that our lives are lived inside the thinnest of biochemical margins. This rude awakening may even be the vestige of some adaptation, the remnant of a capacity developed hundreds of thousands of years ago to respond to some forgotten contingency of prehistoric life—the presence of the sublime triggering the genetic impulse to curl up and wait for danger to pass—but now just an unpleasant paleontological curiosity.

  But then again, maybe not. Maybe this is a visitation from your own distant reaches, the solitariness you’ve been reveling in transformed into loneliness and the memory of an uncomforted childhood, the sudden tempest, reminiscent of the roiling and dangerous household in which you once lived, plunging you into that familiar miasma of fear and self-loathing, into the echoing prison of depression. Maybe, in other words, it is the margins of biography that are narrow. Maybe there is no escape from a story so deeply inscribed.

  Or perhaps it is a visitation of a different order, the intrusion of another unwelcome fact: that just beyond the ersatz poverty of your crude wooden shack lies the real thing and just beyond that a skein of injustice and suffering and exploitation in which you have a hand and that seems illimitable. Maybe what has crept over you is only the hopeless truth behind your ecotourist pretenses, the knowledge that you would rather live with the self-devouring discontents of bad faith than chuck your comfort and your familiar life into the sea. Or the fear that whatever is important to you will crumble, that even love will disappear.

  Or maybe Hippocrates was right all along. Maybe you really do have out-of-whack humors, but they are in a place where scientists haven’t yet thought to look or that their instruments won’t find anymore than a magnet can find feathers. Or maybe it’s karma or the alignment of the planets or the chemicals in your food. Or, as you will think later, standing behind a beautiful young couple kneeling together under a stained glass window in the transept of a church on the mainland, praying (or so you imagine) for a happy marriage or a pregnancy or the good health of a loved one, devotion radiating like sunlight off their bowed shoulders, maybe none of these stories make much sense. Maybe these children of Job—who believe (so you think) that good and bad fortune reflect a heavenly order—are right, maybe hope and despair, pain and consolation are part of the battle between God and Satan, and maybe you should get down on your knees and pray.

  Every one of these accounts of depression—and there are undoubtedly others—can account for this sudden malaise, and each has its uses. I’m not going to tell you which one is right, because I don’t know. I’m just going to tell you to be wary of people who tout certainty at the expense of truth, especially when what they are certain about is something so complex and baffling and weighty: the nature and causes of our suffering and what we ought to do about it.

  Even some depression doctors are beginning to wonder about the truthfulness of their story. They’re beginning in particular to think they might have rendered too much of the world insane. Some of this concern is sparked by business considerations. The widespread distribution of the depression diagnosis, they worry, can result in brand dilution or in other marketing difficulties. Darrel Regier, the American Psychiatric Association’s chief of research, put the problem this way:

  Various critics of the current diagnostic system have characterized the expansion of diagnostic categories as a “guild” attempt to justify payment for any condition a psychiatrist might see in practice, or as fabrications of the pharmaceutical industry to justify the sale of their products.

  Regier went on to point out that the dire estimates of mental illness in the population—in any one year, using DSM criteria, something like 30 percent of Americans qualify for one diagnosis or another—raise some red flags even without the critics. For instance, he wrote, the mental health treatment system is in no way prepared to treat the 100 million patients forecast to meet the criteria every year. This embarrassment of riches could be a public relations disaster.

  Regier is among the psychiatrists who think
the ease of diagnosis is mischief wrought by Kraepelin’s ghost, that running down a checklist of symptoms and concluding that people are sick if they say yes often enough is bound to lead to overestimates. What’s missing, they think, is sufficient consideration of whether and to what extent those symptoms are actually problems for people—“clinical significance,” they call it. This standard was supposed to replace intrapsychic conflict as the übercriterion of mental illness when the DSM-III was revamped in the wake of the homosexuality debacle. But Regier believes, and more psychiatrists are coming to agree, that doctors are not any better at agreeing on how to assess significance than they were at standardizing intrapsychic conflict. Nor are they particularly eager to try:

  Despite the prominence of clinical significance in diagnostic criteria, there is currently no consensus as to how it should be defined or operationalized. In large epidemiological surveys, direct clinical judgment is rarely used because of the high cost of clinical time and the large number of subjects.

  Doctors, in other words, are too busy diagnosing patients to worry about whether or not they are really sick.

  Regier thinks that the data are there to assess clinical significance. Researchers—epidemiologists and clinicians alike—do ask patients how much a given symptom interferes with their lives or whether it ever prompted them to visit a doctor. But the answers aren’t necessarily factored into the final results, so, as I discovered at Mass General, a person who gives little or no indication of significant impairment but who has five symptoms of depression is still depressed. The data remain, however, and Regier and his team extracted them to reassess the outcomes of the major epidemiological studies of depression, the ones that lead to those dire estimates. And it turns out that, once people are ruled out who have the symptoms but aren’t impaired or distressed by them, the prevalence of depression is cut nearly in half.

  This problem has led some psychiatrists to suggest that the current categorical approach to diagnosis should be replaced with a dimensional approach, in which only people at the extreme end of the symptom spectrum, the ones with the most symptoms that rise to the highest levels of clinical significance, would receive diagnoses. Regier’s position as vice chair of the DSM revision committee has led some psychiatrists to worry that if this happens, the disorders at the mild end of the spectrum will soon go the way of homosexuality and neurosis. These doctors have already struck back with some statistics of their own, showing that the mildly symptomatic will eventually get worse. We don’t wait for people with high cholesterol and blood pressure to have a stroke before we diagnose and treat them, they argue, so why should we wait for the mildly depressed to cross the threshold?

  The dimensionalists suggest that such people ought to get treatment and that any unmet need this creates “should be addressed by developing comprehensive triage rules that allocate available resources based on evidence-based assessments of the cost-effectiveness of available treatments.” Interestingly (and speaking of a “guild attempt” to increase business) this proposal not only casts the net wide; it also creates an argument for early assessment (which can only increase the numbers of diagnoses) and preemptive treatment—much of which will no doubt be with medication administered by psychiatrists, usually the cheapest of the available resources.

  Whichever way this dispute breaks, one thing is certain: you are very unlikely to hear much about the dispute over mild disorders. The squabbles over neurosis and homosexuality taught the American Psychiatric Association a lesson about airing the family linen in public, so it has made people serving on the DSM-V committees sign a confidentiality agreement as a condition of participation. That’s too bad, not only because we’ll miss a debate bound to be as absurd as it is enlightening, but also because from what I can gather from A Research Agenda for DSM-V, a book the APA brought out at the beginning of the planning process for DSM-V in 1999 (a mere five years after DSM-IV was released; you would think that they’d realize how all this dithering looks to the rest of us), the guild is going to make the zero validity problem part of its proceedings as it fashions a new diagnostic manual:

  The major problem for mental disorders as currently defined is that their causes and pathophysiological mechanisms remain largely unknown. It is expected that, at some point in the future (perhaps decades from now), the pathophysiological states predisposing or contributing to major mental disorders will be identified… Once it is possible to define a mental disorder based on the identification of its underlying pathology, then it would surely make sense to follow the course of other medical conditions and have the presence of the disorder be based solely on pathology and not on the effect this pathology exerts on the individual’s functioning.

  It would be nice to hear psychiatrists acknowledge in public that even though they’ve been telling people for two decades that they know what the underlying pathology of depression is, they really don’t. But with the pathophysiologically based classification system that the book says will solve this problem decades away, it’s no wonder that the APA wants to keep a tight lid on the proceedings. They don’t want us to know that they’re still working off that promissory note until they’re ready to put paid to it.

  * * *

  There is some evidence that reform-minded doctors should be careful what they wish for. The transformation of psychiatry into clinical neuroscience may hold some unpleasant surprises for them. Consider what psychiatrist Max Fink has been saying recently.

  Fink thinks that the APA took a disastrous wrong turn when it resurrected Kraepelin’s categorical approach but left buried one of his most important categories: melancholia, a diagnosis that Fink thinks fits the subgroup of the depressed who feel anxious and despondent for no particular reason, who wring their hands and sleep all day, who are delusionally guilty and self-reproachful—patients like the woman I’ve called Ann. This, Fink points out, is the cluster of symptoms that Hippocrates originally observed, that has been reported by Kraepelin, Freud, Meyer, and Kuhn (and nearly anyone else who has bothered to look). The disease, as Fink sees it, has none of the Chinese menu fuzziness of the DSM’s major depressive disorder, but instead has four symptoms, all of which must be present for the diagnosis. And, best of all, the fourth criterion is a lab test—either a sleep study that shows irregular brain wave activity or an endocrine panel that reveals abnormalities in cortisol, a hormone whose levels increase with stress. Fink’s melancholia, in other words, is a disease in the modern sense—a form of suffering with a specific biochemical signature. To Fink, this means that it would behoove his profession to restore it as a diagnosis in the DSM-V. It could even be the flagship disease in that longed-for pathophysiologically based classification system.

  Fink is not the first doctor to propose cortisol tests to verify depression, and they are compatible with current neurochemical theories, which see depression as a stress reaction gone amok. But studies have shown that fewer than 50 percent of the subjects who meet DSM criteria for depression turn up positive on the bioassays. On the other hand, when researchers weed out the nonmelancholics from the subject pool, then that number goes up to 70 percent or higher. Fink also points out that studies showing homogeneous brain chemistry or structure tend to be strongest when the subjects are more severely depressed, which suggests, he says, “that what is now considered the pathophysiology of major depression is best restricted to melancholia.” Make the category less heterogeneous, in other words, and it may actually start to have some scientific integrity.*

  But not without a cost—market share. Melancholics in Fink’s sense make up only a small portion of people who meet the DSM criteria for depression. But that’s not the only reason that the depression industry is not beating a path to Max Fink’s door. It’s also because Fink, who in his late eighties, is one of the world’s leading proponents (and practitioners) of electroconvulsive therapy, which is a highly effective treatment for melancholia—as doctors have known since the 1940s. But while doctors continue to provide ECT, very quietly,
it’s hard to imagine who is going to pay for clinical trials for a device that lost its patent protection long ago, and which has such a terrible reputation.

  Nor are the drug companies likely to get behind Fink’s proposal anytime soon. They do have a cure—tricyclic antidepressants, whose effectiveness with melancholia approaches that of ECT and far outpaces the SSRIs. But they’re also off-patent; there’s not much money to be made there either. Some electricity-based therapies less dramatic than ECT—deep brain stimulation, transcranial magnetic stimulation, and vagus nerve stimulation—have shown promise for melancholia, but these are hardly blockbuster treatments, especially if the patient pool is limited to those who fit Fink’s diagnostic scheme. Given the fact that the burial of melancholia was essential to the expansion of the depression diagnosis, it is very unlikely that without the lure of large profits the industry is going exhume it anytime soon.

  Fink’s proposal to restore melancholia to the DSM suggests a reason for the poor performance of SSRIs in clinical trials. Doctors know that the subjects who show the most melancholic symptoms do worse in clinical trials than the other patients. And the HAM-D, the test that measures the performance of SSRIs, was standardized on hospitalized depressives, many of whom would very likely meet Fink’s criteria for melancholia. The drugs, in other words, may be good for something, just not what the doctors are looking for.

  Actually, the drug companies already know at least one thing SSRIs are good for. They’re just not sure they want to make a big deal about it.