For those in the field of mental health, the debate about the efficacy of pharmaceutical medications has been an enduring and uncertain one, and this debate can sometimes end up complicating treatment, outcomes, and even attitudes toward what it means to be well. In his extraordinary new book, Ordinarily Well: The Case for Antidepressants, Peter D. Kramer delves into this debate, taking a rare and unbiased look at the question: Do antidepressants work?

Kramer, the author of the widely popular Listening to Prozac, uses his impressive clarity and insight to study the science that has influenced antidepressants. The question he encourages us to ask is not whether antidepressants work, but rather, what do we mean when we say that they work?

One problem antidepressants have always had, Kramer notes, is that their efficacy has hinged on meta-analysis studies. What these studies cannot possibly measure are the individual human affects. Kramer points to the case of Adele, his first patient in a private series whom he treated with psychotherapy and antidepressants. While Adele showed only subtle improvement, her results led Kramer to a profound conclusion: antidepressants (specifically imipramine) had made Kramer a more competent therapist.

The path that led antidepressants to become the part of mental health treatment they are today hasn’t always been smooth. Kramer points to a “biting commentary” by Doris Y. Mayer, an accomplished psychiatrist. The piece, titled, “Psychotropic Drugs and the Anti-Depressed Personality” made the argument that antidepressants numb the full range of emotions — especially the distressing ones. Experiencing and learning to tolerate distress, according to Mayer, is a key factor in learning to overcome depression and avoid the malaise characterized by anti-depression.

The counterpoint to Mayer’s position is the case of Ray Osheroff. Osheroff was a kidney specialist and entrepreneur who became depressed, and when medication didn’t seem to alleviate his depression, he checked into Chestnut Lodge, a psychiatric hospital in Rockville, Maryland. Upon entry, Osheroff explained that he had a contract worth millions and needed to return to the office in six months. He also asked to receive antidepressant medication. Osheroff was denied medication, lost control of his business, and ultimately his marriage.

Shortly thereafter, a friend of Osheroff’s had him moved to another hospital, Silver Hill, in Connecticut, where he was given antidepressant and antipsychotic medication and improved in three weeks, being discharged in three months and returning to medical practice. Osheroff later sued Chestnut Lodge, and the case, Osheroff v Chestnut Lodge, was settled in Osheroff’s favor and became a sea change in how medications should be prescribed. Hospital staff could now be held liable if needed psychotropic medications were withheld.

The piece by Mayor and the Osheroff case are just two examples of many that Kramer presents. He doesn’t make an argument for either one, he simply offers them as points for us to ponder. He does state that medications work and that some effects simply cannot be measured with clinical trials. Kramer tells us of Caroline, a patient who initially came to see him out of concern for her marriage, but who had also been distressed over her inability to do her work as a copywriter due to a mental fog. With medication, Caroline’s thoughts returned to their usual clarity and she found that her gift with words also returned, and shortly thereafter, she was able to resume her position. The point that Kramer makes is that, “A great harm of depression was that it had blocked her from exercising her talents.”

Antidepressants have another integral role in patient health: they stabilize patients so that they can work through their distress. And these effects may not be so accurately measured through FDA studies. As Kramer writes, “Finally, here’s my take on FDA studies: They performed their job, allowing the agency to identify useful medicines, ones that patients can live with, ones that have transformed the face of depression. Beyond that, trials are a lousy source of information about antidepressant efficacy…”

What FDA studies don’t measure, Kramer tells us, are social effects, such as calling a friend, having that friend respond favorably, feeling more relaxed, friendlier, and more willing to reach out to others. While antidepressant medications are far from flawless — Kramer notes that in general practice psychiatry, we still live with failure — when studies cast a broader net, incorporating those who have severe depression and milder forms, we often find that medications do work quite reliably. “Over three quarters of those who start treatment enjoy substantial improvement,” writes Kramer.

The question Kramer asks is: Can a doctor rely only on randomized trial results and still treat real people? According to Kramer, perhaps not. While Kramer has made a practice of studying and measuring the effects of antidepressants, he is also deeply aware that the one thing that may continue to evade clinical research is the salubrious effect of the clinical encounter. In his words, “For me the clinical encounter is a sacrament.”

Ordinarily Well: The Case for Antidepressants
Farrar, Straus and Giroux, June 2016
Hardcover, 336 pages
$27.00

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