The Antidepressant Wars
A Fierce Debate that Ignores Patients
May 3, 2012
May 3, 2012
13 Min read time
I began to think of suicide at sixteen. An anxious and driven child, I entered in my mid-teens a clinical depression that would last for 40 years. I participated in psychotropic drug therapy for almost 30 of those, and now, owing in part, but only in part, to the drug Cymbalta, I have respite from the grievous suffering that is mental illness.
As a health policy scholar, I understand the machinations of the pharmaceutical industry. My students learn about “me-too” drugs, which barely improve on existing medications, and about “pay-for-delay,” whereby pharmaceutical companies cut deals with manufacturers of generic drugs to keep less expensive products off the market. I study policymakers’ widespread use of effectiveness research and their belief that effectiveness will contain costs while improving quality. I appreciate that randomized controlled trials are the gold standard for determining what works. Specifically, I know that antidepressant medication is vigorously promoted, that the diagnostic criteria for depression are muddled and limited, and that recent research attributes medicated patients’ positive outcomes to the placebo effect. In my own research and advocacy work, I take a political, rather than a medical, approach to recovery from mental illness.
Cymbalta in particular epitomizes pharmaceutical imperialism. Approved by the FDA in August 2004 for the treatment of major depressive disorder, it has since gotten the go-ahead for treating generalized anxiety disorder, fibromyalgia, and chronic musculoskeletal pain, including osteoarthritis and lower back pain. It remains under patent to Eli Lilly.
I would not have been surprised if Cymbalta had not worked for me or had not bested the myriad drugs and drug combinations that came before. My path through clinical depression is strewn with discarded remedies. “Who are these people?” I wondered about patients who were said to achieve happiness with the first pill and therefore to violate societal notions of identity and independence. I was just trying to get out of bed, and although my first antidepressant, at age 26, had a strong positive result, it also had incommodious side effects, and relief was tentative and partial. Decades of new and evolving treatment regimens followed. I have been treated with every class of antidepressant medication, often in combination with other psychotropic drugs. Some drugs worked better than others, some did not work at all, and some had unendurable side effects. But Cymbalta did not disappoint, and now I have become a teller of two tales, one about health policy, the other about health.
• • •
Like many depressed people, I resisted the idea of psychotropic medication. I was deeply hurt when my psychotherapist suggested I see a psychiatrist about antidepressant drugs. How could she think I was that crazy or that weak? But she said she was concerned for my survival, and I eventually did as she asked. I became an outpatient at a venerable psychiatric hospital, where I found a kind stranger who knew my deepest secrets and wanted to end my suffering. He wrote a prescription, and thus began my 30-year trek.
Depression is sometimes confused with sadness. Many depressed people are very sad, as I was, but the essence of my depression was feeling dead among the living. Everything was just so hard. William Styron describes depression as “a storm of murk.” Andrew Solomon’s atlas of depression is titled Noonday Demon. I too found depression to be fierce, wrapping me in a heavy woolen blanket and mocking my attempts to cast it off. The self-loathing was palpable; it felt like I was chewing glass. I sensed that other people were seeing things I did not, and apparently they were, because when I began my first course of antidepressants, it was as if someone had turned on the lights. It did not make me happy or even content. The world simply looked different—brighter, deeper—and I was a part of it. I saw something other than the impassable flatness and enervating dullness, and I was amazed.
My progress came at a cost. In the late 1970s, before Prozac, antidepressant medication was seldom spoken of. The people I told about my treatment echoed my first reaction and sang throaty choruses of why-don’t-you-just-cheer-up and won’t-this-make-you-a-drug-addict. I was also drowsy after I ate, my mouth was always dry, and when a second medication was added, I began to lose control of my limbs and fall down. I insisted to my psychiatrist that it was the second drug that was causing me to fall. A champion of that one, he instructed me to discontinue the first. I responded in the way only privileged patients can: I went around him, using personal connections to wrest an informal second opinion from a resident in the lab run by my psychiatrist’s mentor. My doctor was convinced, and a little embarrassed, and we both learned something about therapeutic alliances.
In another city, another psychiatrist took up my case. We tweaked antidepressants and mood stabilizers, reintroducing the drug that had made me fall, this time in tiny doses. I fell less often, but ultimately gave it up, and when I left this psychiatrist to move again, we acknowledged that I was, in the words of mental health expert Gerald Klerman, better but not well.
My depression felt like chewing glass.
Then, more than a year after I had seen him for the last time, this psychiatrist phoned to say that there was a new drug I ought to try. It was called Prozac, and it worked differently from, and better than, the other drugs I had been prescribed. An exuberant man, he was especially excited about this addition to his therapeutic arsenal, and my new psychiatrist made the switch.
Prozac actually was more effective than the other drugs I had tried, and my dry mouth was gone. When more drugs like Prozac were introduced, I was switched to each of them in turn, still in pursuit of more thoroughgoing relief. This was the ethos of my treatment with every psychiatrist I visited: I could feel better, the drugs were getting better, and we would just keep trying.
In the years that followed, we just kept trying. I would remain on a regimen until my psychiatrist proposed another, and, looking back, I was remarkably game. I was treated with monoamine oxidase inhibitors, which can be fatal in combination with some foods, and a famous psychiatrist in Manhattan prescribed a drug sold only in Canada. When a medication produced double vision, my psychiatrist suggested I drive with one eye closed. Drug cocktails deteriorated into over-medication. I tried to enroll in a clinical trial that would implant electrodes in my brain, but it was already full. There was only one remedy I rejected outright: electroconvulsive therapy. I was told by other patients about their memory loss, and I needed a good memory to do my job.
I was doing relatively well on one antidepressant when I saw a television advertisement for Cymbalta. A sophisticated viewer, I knew not to be taken in, but the ad spoke of depression’s physical pain—something I had long experienced and to which my psychiatrists paid little attention. I was a rheumatology patient at the time; I was almost always achy, and it worsened when my depression did. My psychiatrist maintained that we had tried everything worth trying, but I was intrigued by the Cymbalta ad: these people knew something about me. Fully aware of my complicity with big pharma, I pressed my psychiatrist to prescribe the drug, and he agreed unenthusiastically to do so. Once I started on Cymbalta, I never needed to visit him or my rheumatologist again. The effects of this drug were different in degree and in kind, and I finally felt well, both physically and mentally. For the past four years, Cymbalta has worked for me, though I recognize that the improvement might be temporary.
Intertwined with this pharmaceutical saga are other, related biographical threads. Perhaps most importantly, I have been a psychotherapy patient off and on since age sixteen, and for the past fifteen years, I have participated in psychoanalytic psychotherapy to repair the effects of childhood trauma. This therapy has changed me profoundly, but Cymbalta changed me in a different way, and my psychotherapist agrees. The relative merits of medication, psychotherapy, and their combination are debated in the literature, but in my case, there was plenty of work to go around. There were also leaves of absence, hospitalizations, support groups of various stripes, and board membership in a mental health consumer group that refused, on principle, badly needed funding from the pharmaceutical industry.
What difference has Cymbalta made? There is, I think, no way to convey the anguish of mental illness to someone who has not experienced it. In the poem “Having It Out with Melancholy,” Jane Kenyon writes, “A piece of burned meat / wears my clothes, speaks / in my voice, dispatches obligations / haltingly, or not at all. / Is tired of trying.” Solomon’s father had to cut his lamb chops for him. In You Are Not a Stranger Here, Adam Haslett’s fictional character Paul tries to find meaning in his depression because “the opposite has always seemed more frightening to him, lonelier—the idea that so much of him was a pure and blinded waste.”
The suffering of depressed people does not justify the misdeeds of the pharmaceutical industry, nor does it minimize the drugs’ deleterious effects on some patients. However, discussion of antidepressants’ value should not forget this suffering or imagine that it is insignificant or suspect. In my experience, antidepressants are neither happy pills nor placebos; they are the difference between life and living death.
• • •
Evidence for the uselessness of antidepressants has figured prominently in recent health discourse. In the New York Review of Books, Marcia Angell, former editor of the New England Journal of Medicine, favorably reviewed works that challenge the findings of industry-funded FDA trials for several antidepressants. The books reviewed have titles such as The Emperor’s New Drugs: Exploding the Antidepressant Myth and Anatomy of an Epidemic: Magic Bullets, Psychiatric Drugs, and the Astonishing Rise of Mental Illness in America.
Psychiatrist Peter Kramer responded in the New York Times “in defense of antidepressants,” noting, among other things, possible problems with the critics’ own research. The day after Kramer’s article appeared, I was contacted by a national mental health consumer group and asked to petition the Times to print a rebuttal to Kramer by Robert Whitaker, author of Anatomy of an Epidemic. Whitaker wrote that Kramer’s misrepresentations of his findings “took my breath away.”
At the heart of this fevered back-and-forth is the re-analysis of existing efficacy data, including those provided by drug companies to the FDA. Simply put, efficacy—and broader effectiveness—research relies on statistical analysis of clinical trial data to determine if differences in outcomes between treated and untreated groups occur at a rate better than chance. These are differences, however, between the average outcome of patients in each group, and they tell us nothing about whether some kinds of patients do better or worse, much less about the responses of individual patients. A 2009 review of the randomized controlled trials literature found that only 29 percent of trials tracked whether different kinds of study subjects had different outcomes.
Cymbalta epitomizes pharmaceutical imperialism—but it works for me.
Antidepressant trials sometimes do group subjects according to the severity of their symptoms, but severity levels are assigned using a brief and inadequate questionnaire. I have been scored this way many times, but I never felt the score sheet’s priorities—it asks yes-or-no questions about sleeplessness and suicidal thoughts, among other symptoms—were my own. Psychiatric patients across diagnoses report dissatisfaction with the researcher-friendly but existentially insignificant measures on which effectiveness findings are often based.
Furthermore, the diagnosis of depression itself is based entirely on symptoms, so depressed trial subjects are considered comparable despite genetic and etiological differences that might bear on the effectiveness of a given treatment. These limitations of clinical research may be unavoidable in some circumstances, but they should be admitted to at the very least. They might also engender among all antidepressant warriors an intellectual humility and attentiveness to patients that is currently rare.
The intensity of the current debate unsettles me. I understand—and have been directly affected by—the greed of the pharmaceutical industry, the indeterminacy of clinical studies, and the substitution of chemotherapeutics for psychotherapeutics in psychiatry and health insurance policies. I lament, with my colleagues, the cost of unnecessary care and denounce, with my comrades, the toll of unnecessary drugging. I remember an earlier, mirror-image discussion of Prozac, and it was just as heated. In the 1990s, this drug (one of those debunked in The Emperor’s New Drugs) was believed to be so effective, even in people without depression, that it might constitute unjust and unaffordable enhancement rather than legitimate treatment. I once, in a spirited exchange, told a bioethicist colleague that if my antidepressant made me inauthentic so his eyeglasses made him.
Medications that affect the mind seem to discomfit us deeply, culturally, viscerally. And so do the people who need them: psychiatric patients have gone, in this discourse, from covetous of an unfair advantage to oblivious to a colossal con. I am not sure which characterization I prefer, but I know my heart will break when a friend in the grip of depression forgoes medication—not because it is not right for her, but because it is only for cheaters or fools.
Most parties to the debate agree that antidepressants can be effective for severely depressed patients such as me, but selfishly I fear the rhetoric of antidepressant uselessness will influence the pharmacy policies of my health plan. At present I am charged an inflated copayment for Cymbalta because my health plan claims it is no more effective than generic antidepressants. I am not privy to the basis for this determination; I do not know if it is based on average treatment effects, the preferences of plan professionals, or an overriding concern for cost. I do know that it does not include my experience, and when I queried the plan about an appeal, I was told I could appeal but should not bother: there are no successful appeals. The plan representative was unmoved by my savings on psychiatry, rheumatology, and hospitalization. She intimated that it is just too hard to satisfy individuals and that the plan has enough to do managing costs.
The antidepressant wars will continue. The ineffectiveness theory is already popular with the press, pharmaceutical industry critics, and elements of the mental health consumer movement. I imagine it appeals to health care payers, who generally escape notice in the antidepressant discourse. For payers, who live by the profit motive or under public-budget constraints, findings of ineffectiveness can justify restricting or denying access to antidepressants, even by patients who benefit, and thereby generate substantial savings.
Some doubt is, of course, reasonable. Our knowledge of the many maladies we call depression is rudimentary, and our technologies of knowing are imperfect. I expect, with Thorstein Veblen, that every research answer will yield two questions, and I look forward to more and better answers. I hope the debate will create healthy skepticism among patients and practitioners. I worry it will call into question the already discounted experiences of mentally ill people.
My case is individual, but it is not unique. I have known many depression patients, and their stories also tell of long, hard slogs through antidepressants that do not always work. They are not the lazy, over-consuming, morally hazardous patients of some health policy literatures, but many are afraid to speak publicly about their medications for fear of disclosing their diagnoses and of damaging relationships and careers. I am sure there are people taking antidepressants for the wrong reasons, and perhaps the antidepressant wars will encourage them to re-evaluate. The debate must make room for the rest of us, though—the ones for whom effectiveness and ineffectiveness have been the research questions of our lives.
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May 03, 2012
13 Min read time