Ordinarily Well: The Case for Antidepressants

Kramer Cover Crop

Peter D. Kramer’s Listening to Prozac made him a psychiatric superstar. His 1993 bestseller was an erudite disquisition on the newly popular antidepressant, the biology of human personality, and the ethics of medicating people to make them “better than well.” Kramer coined the phrase “cosmetic psychopharmacology” to denote the use of personality-enhancing drugs and suggested that the notion raised questions about the (mutable) nature of the self.

In Against Depression, Kramer, who is now clinical professor emeritus of psychiatry and human behavior at Brown University, addressed both the culture and biology of the disease. His attack on the association of depression with creativity and the glamorization of melancholia arguably overstated the case. (Is anyone really for depression?) But the book usefully explored critical questions about its nature and origins, portraying depression as a progressive disease involving cell damage and loss of resilience.

His new book Ordinarily Well serves as an indispensable pendant to those two volumes. It brilliantly dissects decades-worth of antidepressant drug trials, while touting the value of clinical observation and practice. At best, Kramer writes, research and patient care comprise a “virtuous dialectic,” each informing the other.

Kramer’s prime target is the view that antidepressants work little better than placebos, especially in treating milder depressions. Assessing the literature and drawing on his own experiences with “dramatic remissions” in otherwise resistant patients, Kramer insists otherwise. He argues forcefully that selective serotonin reuptake inhibitors (SSRIs) such as Prozac, as well as other antidepressants, are invaluable tools in the psychiatric arsenal.

There is, as he would concede, some irony in Kramer’s embrace of pharmaceutical remedies. A veteran of psychoanalysis, he trained as a psychotherapist and remains committed to it in his practice. He has written extensively about both Freud (in a recent biography) and the art of talk therapy (Moments of Engagement, Should You Leave?).

Kramer accurately describes Ordinarily Well – the title refers both to drug efficacy and patient health – as his most technical book. In its pages, he ranges over such relatively arcane matters as study design, placebo effects and statistical analysis. It helps that he is a clear, patient and often elegant writer, with a predilection for circling back to his principal points. But his sophisticated argument demands a willingness to grapple with nuances of the construction, interpretation and limitations of drug trials – fascinating, as he predicts, but hardly beach reading.

The book’s other emphasis – on the importance of clinical judgment and its symbiotic relationship with research – is easier to grasp. Using modified case histories, Kramer discusses situations in which antidepressants lifted a patient’s mood enough to make both effective psychotherapy and life change possible. Beyond diagnosis and prescription, he suggests that the doctor’s role is to “interrogate the literature, try new approaches, note results, revise their sense of what’s plausible, and read further.” Improvisation and pragmatism are key: “Clinicians,” he writes, “need to act.”

Kramer starts with some history, crediting the invention of the modern antidepressant to the Swiss psychiatrist Roland Kuhn, in 1956. While testing a drug called imipramine as an antipsychotic, Kuhn found that its real value lay in jolting patients from depression. But the scientific meat of Ordinarily Well is Kramer’s examination of research trials. He introduces the familiar notion of double-blind, randomized placebo-controlled trials — the gold standard — and shows how complicated achieving that standard can be. He also discusses the Hamilton scale, the imperfect, subjective means by which psychiatrists rate the severity of depression.

He explains statistical concepts such as “effect size” (“how far treatment moves those who receive it”) and shows that “additivity” – a way of toting up combined effects and also subtracting one from another – doesn’t always apply, thereby skewing test results. And he notes that “meta-analyses,” selective reviews of numerous studies, can err by both inclusion and exclusion. Kramer finds just such a flaw in the 1998 essay, “Listening to Prozac but Hearing Placebo,” which he says launched the contemporary debate over the efficacy of antidepressants. He calls the paper, referencing his book and lead-authored by the psychologist Irving Kirsch, “an act of provocation.”

Overall, the list of research challenges Kramer cites is long and not limited to the much-noted problems of drug-industry-financed studies. One hurdle is “baseline [Hamilton] score inflation,” when volunteers seeking free pharmaceuticals or therapy initially exaggerate their symptoms. Another is differential dropout rates between groups under study. Then there are factors that inflate placebo effects, such as more-than-minimal supportive therapy and the benefits of social contact. Add to that the subjectivity of the rating scales themselves, as well as the fallibility and biases of the raters.

It’s all a bit head-spinning, but Kramer’s main points anchor the reader. From both the studies and his own practice, he concludes: “Antidepressants provide dabs of light in what remains a gray pointillist canvas.” He notes that he still favors “common sense over formal evidence” at times – specifically, in using psychotherapy as an adjunct to medication even when studies show no advantage to the combination.

Finally, Kramer offers a lovely humanist observation on the complexities of combating depression in complex environments. “It is not only medicine that maintains well-being,” he reminds us. “Once we function competently, the world may pitch in.”