View attachment 50846 Several years ago, in the middle of reading volume five of The Princess Diaries to our elder daughter, my wife came to a passage about a dog who is so anxious when left alone that he licks himself until his hair falls out. The royal veterinarian has prescribed Prozac, but the young princess thinks the dog’s real problem is that it lives with her grandmother: “If I had to live with Grandmère, I would totally lick off all my hair.” Our daughter was curious about the medication, which she had never heard of. “Wouldn’t it be wonderful,” she said, “if there was something like that for people?”
There is, of course, something like that for people. It is prescribed by sober clinicians, dismissed by critics who wouldn’t give it to a dog, and puzzled over by a public unsure whether it is a life-changing medication or a fairy-tale invention. The confusion is understandable. In 1993, the writer-psychiatrist Peter D. Kramer published Listening to Prozac, his best-selling examination of a pill that promised to revolutionize the treatment of anxiety and depression.
In 2010, the Harvard researcher and psychologist Irving Kirsch published The Emperor’s New Drugs: Exploding the Antidepressant Myth, a data-fueled argument that was lauded in a New York Review of Books essay called “The Illusions of Psychiatry” and featured on 60 Minutes, as well as in a Newsweek cover story. “Studies suggest,” the article reported, “that the popular drugs are no more effective than a placebo.”
Can it really be that Steve Martin’s routine from the 1970s—“If you ever get a chance to take these drugs, do it; they’re called placebos!”—sums up the state of antidepressants in the 21st century? The short answer is no. But a longer answer is required, and Kramer has written Ordinarily Well: The Case for Antidepressants to address what he feels is a destructive level of ignorance and confusion about the class of drugs known as selective serotonin reuptake inhibitors, or SSRIs.
To state Kramer’s position bluntly, SSRIs work—not all the time, and not for all people, but in lots of ways for lots of people. How they work remains a partial mystery, and how well they work has a subjective component—as do the afflictions the drugs treat—but murky borders do not mean there is no country. Pharmaceutical companies may have pushed a cartoon claim of “chemical imbalance” to suggest that some people need supplementary serotonin the way others need extra iron, but Kramer bases his assessment on 30 years of clinical experience as well as his own immersion in the literature of drug trials.
Kramer is, however, a reluctant warrior, or perhaps more accurately a cautious one. He has doubts of his own about the unhealthy interdependencies of Big Pharma, doctors, and insurance companies. He is disturbed by flawed drug trials. He takes seriously worries about overprescribing and other “medical horrors.” Yet he pushes back, arguing that inadequate data from flawed trials are reason to design better research, not to discount the efficacy of drugs.
He criticizes the ease with which statisticians, aggregating disparate studies, discount the effects noticed by doctors who “don’t see averages; they see patients.” And he keeps the big picture in view: “Almost a third of American adults with major depression receive no medical attention for it.” His book is a response not merely to that haunting figure but to the polarized and reductionist debate that casts antidepressants as good or evil, all-powerful or inert. This may explain why he has chosen a title so unobtrusively anodyne that I had to double-check it just now to see whether I got it right.
But Ordinarily Well is an ambitious, persuasive, and important book. Kramer looks from many angles at the nature of the evidence—at what goes into gathering it, and at the ways it is read and misread, applied and misapplied. He doesn’t just make a case for antidepressants. He makes a case for psychiatry itself as a humanistic science that bridges the impersonal ideals of the laboratory and the pragmatic exigencies of clinical intervention. He is defending treatment—drugs, psychotherapy, or both—that relies on imperfect tinkering.
And he is demonstrating why psychiatry’s improvisational nature is not a failure of rigor or a rejection of research but a necessary expression of humility in the face of a system so complex that we don’t know where the brain stops and the mind begins (or whether there even is such a boundary).
View attachment 50848 Psychiatry has lived through schismatic times before. Freud abandoned neurology to devise a closed, self-affirming system of applied mythologies. By the middle of the 20th century, psychoanalysis dominated psychiatry. Mothers of schizophrenics were informed that their parenting style caused their children’s illness. Meanwhile, a handful of maverick scientists at the other end of the spectrum turned away from such barbarism to target the brain directly; they were called lobotomists.
Lobotomists, though wrong to stick ice picks in people’s heads, were right about where the trouble lay. Psychoanalysts, though wrong to ostracize anyone who even suggested testing their methods empirically, were right about the importance of inner conflict and family constellations, and about the vital role that the therapeutic relationship can play in healing. Antidepressants, along with antipsychotic medication, helped restore psychiatry’s scientific credibility without resolving its internal debates.
Lobotomists, though wrong to stick ice picks in people’s heads, were right about where the trouble lay.
Kramer came of age as a physician during the reintegration of the field’s biological and psychoanalytic heritage. In Ordinarily Well, he recalls being a Harvard medical student in the 1970s: “In Boston, recourse to psychiatric medication was thought to signal a failure of imagination on the part of the doctor.” SSRIs didn’t exist yet, but imipramine, the first modern antidepressant, had been prescribed for two decades. The fact that Prozac appeared to lack imipramine’s burdensome side effects—rapid heartbeat, constipation—was one of the things that generated so much excitement after the drug’s approval by the FDA in 1987.
Six years later, when Kramer published Listening to Prozac, his title brilliantly encapsulated a desire to merge two modes of treatment, the talking cure and the pill-taking cure. The word listening affirmed the interpretive role of the therapist that the new drug threatened to eclipse. Kramer expressed concern about what he called “diagnostic bracket creep”—the widening of diagnostic categories to facilitate easier prescribing—and coined cosmetic psychopharmacology to describe the phenomenon of patients who were starting to feel “better than well.” The phrase was freighted with the moral unease of a doctor rooted in an older analytic world where change was earned the old-fashioned way—slowly.
The energy of Listening to Prozac—a sort of exuberant ambivalence—was mistaken by many for breathless endorsement, and the antidepressant’s fame was frequently attributed to Kramer after the fact. In truth, the drug had already endured a wild ride in the press—extravagant praise followed by backlash. In his introduction, Kramer summed up the drug’s first six years as if a turbulent epoch had ended and the time for sober reflection had arrived:
Prozac enjoyed the career of the true celebrity—renown, followed by rumors, then notoriety, scandal, and lawsuits, and finally a quiet rehabilitation. Prozac was Gary Hart, Jim Bakker, Donald Trump. Kramer was right to recognize the drug’s celebrity power but wrong to imagine that common sense, sound judgment, and experience would guarantee a low-profile, unembattled future for Prozac. In short, the invocation of Trump proved prophetic.
Kramer writes with a measure of guilt in Ordinarily Well about his desire, after publishing Listening to Prozac, to escape his association with the celebrity drug. He wrote a novel, investigated other matters, saw patients, taught (he is a professor at Brown University’s medical school). But Kramer’s wagon was hitched to a psychopharmacological star 25 years ago, and in the past decade, he found that he could no longer ignore what he felt had become a veritable assault on antidepressants.
His thankless but bracing challenge in his new book is to explain how “evidence-based medicine”—a movement that took off in the 1990s with the laudable goal of grounding clinical recommendations in objective studies—has facilitated the opposite of its original intent. It has, he believes, shrunk the circle of allowable evidence and encouraged a blinkered certitude inimical to good medical science.
Determined to meet Prozac’s critics on their own terms, Kramer curbs his natural storyteller’s inclination, corralling personal reflections and case histories into discrete sections called “interludes” as he delves into serious lab work. The nether region of Ordinarily Well is less fun than the Freudian underworld where bird-headed gods dance with your mother; it is also more frightening—at least for humanities majors. It is the dwelling place of randomized trials, effect sizes, blind studies, confounds, meta-analysis, placebo effects, and the Hamilton scale. But Kramer is an excellent guide as he subjects evidence-based purism—“a near-exclusive reliance on the findings of randomized, controlled, double-blind outcome trials”—to the scrutiny he believes it needs.
Antidepressants work—not all the time, and not for all people, but in lots of ways for lots of people.
Randomized trials were a huge medical advance in the 1940s, but Kramer explains that Sir Austin Bradford Hill, the statistician who pioneered the new design, later warned about their limitations. When it came to testing disorders like anxiety and depression, with subjective symptoms, Hill saw that “to optimize outcomes, doctors would need to adjust doses and observe responses,” Kramer writes, and “the clinician’s perception might be the most accurate gauge of results.” This is precisely what the Swiss psychiatrist Roland Kuhn—who discovered imipramine—did in 1956.
Both a researcher and a clinician, he was able to prove the efficacy of an antidepressant that even 60 years later remains a standard, because he saw the patients in his asylum every day and carefully calibrated his trials to his patients’ needs, and to their responses to his recalibrations.
To demonstrate how far we have strayed from Kuhn’s hands-on, informed investigations, Kramer undertakes a fine piece of up-to-date reporting—a visit to a private drug-testing center that conducts trials, primarily with antidepressants, for pharmaceutical companies. He turns to storytelling not to dismiss the value of medical statistics, but to place before the reader’s eyes the main ingredient that never makes it onto the package label: people.
It is one thing to be told just how variable placebo effects can be—changing with the weather, the economy, the nature of the “minimal supportive psychotherapy” supplied along with the sugar pill. It is very different to eavesdrop on a community of drug-trial subjects who often help recruit one another—generally from a population very different from the one the drugs are intended for. Some are homeless, others merely unemployed and eager for the social environment of the testing center and the $50 or so they are paid per visit.
Many have an incentive to exaggerate the severity of their depression; they can then remain in the study and receive free health care. Others underreport the nature of intractable afflictions in order to qualify for the trial. Listen, along with Kramer, as a subject supplies answers for a checklist, and you’ll understand his “despair of rating scales.”
The rater asks, “When you are in a stressful situation, does your voice quake?”
“Under stress?” Albert’s voice goes up a pitch, cracks, and wavers. “I would say no.”
Kramer is not denying the usefulness of drug trials, but showing how context matters. He also parses the complex reasons FDA tests fulfill their intended purpose (to establish minimal effectiveness and drug safety), yet are a lousy source of information about a drug’s true capabilities, whatever they may be. In other words, extrapolating from FDA data—which critics of medication often do—rather than devising new studies is like using a pass/fail course to determine a student’s caliber.
Ordinarily Well is haunted by battles from psychiatry’s past. Psychopharmacology is often dismissed in language reminiscent of the rhetoric of the anti-psychiatry movement, which flourished in the 1960s and accused psychiatry of duping with dreams, medicalizing ordinary emotions, and treating socially constructed disorders with illusory remedies. Those checklists that Kramer dislikes lent discipline to the Diagnostic and Statistical Manual, which became psychiatry’s ticket back into the scientific community after its hermetic psychoanalytic heyday. By now, most antidepressants are prescribed not by psychiatrists but by general practitioners; the careful combination of listening and prescribing that Kramer champions has become an endangered activity.
None of these tensions negates the importance of his book—quite the contrary—but they may account for a certain melancholy tone. When psychoanalysis lost its mojo, it was still possible to refer to Freud as a tragic philosopher. Kramer doesn’t want to be a tragic philosopher. His whole book is predicated on the possibility of persuasion in the face of great complexity, just as he believes in the utility of antidepressants in the face of all their flaws. He is the kind of practitioner who speaks of antidepressants as “co-therapists” and describes imipramine working in a “courteous” fashion, offering “modest but invaluable relief.” Kramer also works in a courteous fashion, respectful of his opponents and his readers, in whose patience and capacity for reason he places great faith.
All of this gives Ordinarily Well poignant nobility. The author isn’t just defending the essential humanism of psychiatry; he is embodying it.
By Johnathan Rosen - The Atlantic/July-August Edition 2016
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