'Ordinarily Well' by Peter D. Kramer investigates antidepressants

A young woman tells her doctor she's not herself. For the last several months, she has slept poorly, been irritable with her kids, lost interest in sex and can't concentrate at work. She begins to cry. Basic laboratory tests exclude medical disorders, such as an underactive thyroid gland, as the cause for her symptoms. She rarely drinks wine and has never used illegal drugs. She describes her life as ordinary and doesn't believe that talking about it will do her much good; besides, she says she is too busy with work and family for regular therapy visits. Her doctor prescribes an antidepressant drug. Will it help? And if she starts to feel better in a few weeks, will the cause be the chemical properties of the medication or her own belief in its power?

Such questions are at the heart of Peter D. Kramer's new book, "Ordinarily Well." Kramer, a Brown University psychiatrist, is best known as the author of the 1993 best-seller "Listening to Prozac," written in the early years of the newer-generation antidepressant revolution led by Prozac and Zoloft. In that book, Kramer explored the social and ethical implications of a drug that made some of his patients "better than well."

Even in the early 1990s, case reports of increased violence and aggression on Prozac led to skepticism about its "wonder drug" identity. Over the last decade or so, antidepressants have taken further hits, with a spate of reports questioning their effectiveness. In books and essays, some journalists and psychologists have argued that antidepressants are no more effective than placebos while others have gone further and declared these medications intrinsically harmful. These dissenting perspectives came to wider attention when Dr. Marcia Angell, a prominent voice in the medical world, summarized and endorsed them in a two-part 2011 essay in The New York Review of Books.

Kramer's new book — motivated in part by Angell's critique — seeks to restore public confidence in antidepressants through a combination of reporting, research analysis and his own experience with patients. It is not an easy read, but it is certainly an important one for those who seek help for depression and the providers who treat them.

The preface outlines his approach to the subject: "This book is about two influences on medical practice," Kramer writes, "rigorous trials and clinical encounters." Throughout, he explores the dynamic between these two perspectives. At their best, researchers and clinical providers complement one another to deliver top-notch care to suffering people. But too often, these groups operate more like ideologically warring factions.

Kramer spends much of the book examining different aspects of clinical research trials. These studies are the foundation for what is known as evidenced-based medicine, where the goal is to get physicians and other medical providers to rely less on "doctorly experience and more on objective research results." In theory, this approach makes sense. After all, what competent doctor wouldn't want to do things the right way? However, exclusive reliance on this approach assumes a certain infallibility with medical and psychiatric research that largely does not exist.

Take, for example, meta-analysis, a popular type of research study that combines the results of several smaller studies to draw conclusions in the aggregate. The process used to determine which studies to include and exclude can skew the outcomes, either for or against antidepressants. Such is Kramer's take on the research of Irving Kirsch, a psychologist who has received national coverage for his work on the placebo effect and his assertion that antidepressants are essentially glorified sugar pills. Kramer argues that Kirsch selected studies with weaker antidepressants and that some drugs he regarded as placebos may in fact have had antidepressant effects themselves.

Kramer effectively explores other limitations of psychiatric research, including the challenges of finding patients for clinical studies and the resulting tendency to include people who are not really depressed in order to meet enrollment quotas. Here, he takes us inside a for-profit research center where he observes a preponderance of low-income participants, who for the duration of a trial, "enjoy higher income, richer social contacts, attention from doctors and nurses, ... structured days, and a sense of purpose." As Kramer writes, "even on placebo, these patients ought to get better."

While examining the ins and outs of clinical research studies, Kramer also takes us on his personal journey as a psychiatrist, beginning in medical school in the 1970s at Harvard, where, at the time, antidepressants were largely discouraged and classical Freudian psychoanalysis remained the predominant mode of treatment. He describes formative encounters with patients who made dramatic improvements on medication after spending months, sometimes years, making little or no progress in psychotherapy. This pattern continued in his early career, as Kramer describes increasing comfort — and skill — with the use of antidepressants. These anecdotes underscore the value of practical knowledge in treating patients — an attribute that Kramer feels is being increasingly discounted. "I respected clinical experience," he writes. "Why else would I ask colleagues for advice? I wanted my own doctor to have seen a thing or two."

Although Kramer is staunch supporter of the benefits of antidepressant medications, he does briefly acknowledge toward the books' end some of the criticisms and reservations leveled at their use: "I don't doubt," he writes, "that antidepressants are overprescribed, prescribed inaccurately and unthinkingly, prescribed with poor follow-up, prescribed for too long, and the rest." In this regard, he makes special mention about excess use in nursing homes and in the treatment of children and adolescents. Kramer also could have mentioned the reality that most antidepressants are written by non-psychiatrists whose training in mental health assessment is, unfortunately, often quite limited. Further, there is the problem of far-too-many patients also winding up on high doses of anti-anxiety medications such as Xanax and Valium and sleep medications such as Ambien that carry significant risks for abuse in some people.

While acknowledging psychiatry's shortfalls, Kramer asserts that treating depression is not all that different from what is done in other areas of medicine. "Nothing about the try-this-then-that approach to ... minor depression is unusual," he writes. "Consider the treatment of headache. With a migraine sufferer, a neurologist will run a series of practical trials, each using a medicine of limited efficacy, until one does the trick, interrupting attacks, decreasing their frequency and intensity, or preventing them outright." This is undoubtedly true, and Kramer could have gone further with this argument. In many primary care settings, one patient after another is prescribed potent medication on a chronic basis for reflux, back pain and irritable bowel symptoms that are mostly subjective and that might be treatable through diet, exercise and other non-medication interventions. In this regard, psychiatry mimics other medical specialties, yet is often singled out as the lone-wolf of subjective diagnoses and treatments.

Finally, for all of his support of antidepressant medications, Kramer admits he often strays from the standard psychiatric recommendations, as he devotes significant time and effort to psychotherapy, waits longer to start medication, uses it at lower dosages, and tries to wean patients when possible. "My practice fails on many of these fronts, by which I mean that it does not follow the published evidence," he writes. What he is arguing for is the importance of humanism in treating individual patients, something that can't always be captured by the "numbers game" of clinical research.

I approach my patients similarly. I encourage them to try diet change, exercise, psychotherapy and other options — perhaps meditation or yoga — before considering antidepressant medication. Some patients, however, are unable or unwilling to make these changes; others try ceaselessly but make no progress. For these patients, I consider antidepressants, and like Kramer I have seen them provide real relief, both in the short-term and over several years.

So what of that young woman described at the outset, who arrived at the doctor's office with various symptoms of clinical depression. She declines psychotherapy and asks the doctor to prescribe medication. What will happen? In my practice, some patients get better, some stay the same, and some stop due to side effects. That doesn't sound great, but in truth, these outcomes are pretty similar to what happens in much of general medicine, where doctors treat headaches, joint pain and other chronic ailments with varying degrees of success.

If our patient's depression symptoms resolve when she takes medication, the truth is that we in psychiatry won't know exactly why. At this stage of science, the brain remains too complex for full understanding. Also, each person has multiple changing factors that impact his or her emotional life. Kramer's response to this reality is that we don't need all the answers to make our best effort to help someone in true distress. Staying abreast of the current scientific research is important, but we must accept that there will always be an art to treating emotional pain. "Doctors don't see averages," Kramer writes; "they see patients."

Damon Tweedy is a psychiatrist and author of "Black Man in a White Coat."

"Ordinarily Well"

By Peter D. Kramer, Farrar, Straus and Giroux, 310 pages, $27

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