by Peter D. Kramer; New York: Farrar, Straus and Giroux, 2016
310 pages • $27.00 (hardcover)
Peter Kramer’s new book is a persuasive rebuttal to arguments that antidepressant medication is no more effective than placebo. Although clinicians see that antidepressants help patients and save lives, clinical trials continue to show unimpressive differences between drugs and placebos. “Exposés” in the press stigmatize depression and its treatment. Prescribers are uneasy, especially in primary care—the setting in which most depression is treated. Kramer has given us a highly readable explanation of how clinical trials mask what is of critical importance for patients and those who care for them: that antidepressants work “ordinarily well,” that is, about as well as most medical treatments.
Kramer, a practicing psychiatrist and Brown University professor, is the author of 7 books, including the bestselling Listening to Prozac.1 Here he continues his trademark method: searching interrogation of scientific findings reflected against experience with his patients and a history-minded view of the psychiatric Zeitgeist. Great figures in psychopharmacology guide us through the intricacies of clinical trials and meta-analyses to show how inconsistent diagnoses, outdated rating scales, baseline score inflation, and distorted selection of studies for review undercut estimates of drug effects.
Most interesting is the doubt he casts on the “assumption of additivity”—that “true” drug effects can be calculated by subtracting the response rate of a trial’s placebo group from that of its treatment group. To the extent that drug and placebo effects are not additive, the calculations of effect sizes and numbers needed to treat, which are the basis of evidence-based medicine, are flawed. Kramer argues that antidepressants may overwhelm placebo effects in patients who are taking medication so that subtracting placebo responses from drug responses underestimates the actual power of the medication.
Kramer is a fine writer with a gift for the evocative turn of phrase. His patients come alive on the page, and his account of the changes in psychiatry over the past 40 years rings true. Especially memorable is his vivid portrayal of the appalling distortions likely in a commercial drug trial facility that relies on indigent research subjects.
Ordinarily Well does not address the neuroscience of depression or placebo effects, and there is little discussion of the treatment of anxiety and other conditions with antidepressants. Drawing on mostly indirect evidence, Kramer argues that classic placebo effects (ie, patients’ hopeful expectations of benefit) are of minimal importance in treating depression. He overlooks work by Bret Rutherford and others that paints a much more complex picture of expectancy in depression treatment.2
Kramer briefly considers evidence that psychotherapy plus medication is not much better than medication alone. Still, he values his own practice of providing both when needed. As a fellow practitioner of combined treatment, I would have appreciated more exploration of this topic, though in fairness it is beyond the scope of the book.
Kramer’s bottom line is that antidepressants do not deserve the stigma-based and at times self-serving attacks they have received. A second lesson for me is that antidepressant research is truly difficult and that what seems straightforward—such as calculating response rates—may obscure important information for patient care.
My original training was in science. Ever since the controversial 1998 meta-analysis, “Listening to Prozac But Hearing Placebo,” I have harbored a lingering uneasiness about the effectiveness of antidepressants.3 Kramer has calmed these doubts. I recommend Ordinarily Well to everyone who prescribes antidepressants—and to psychotherapists, other health professionals, patients, and members of the public who may have doubts about their effectiveness.
This article was originally posted on 7/25/16 and has since been updated.
Dr Woodward is a psychiatrist in private practice and an Assistant Clinical Professor of Psychiatry at Boston University School of Medicine. His blog, Biology, Psychiatry, and Society, is at burnswoodward.com.
1. Kramer PD. Listening to Prozac: A Psychiatrist Explores Antidepressant Drugs and the Remaking of the Self. New York: Penguin Books; 1993.
2. Rutherford BR, Wager TD, Roose SP. Expectancy and the treatment of depression: a review of experimental methodology and effects on patient outcome. Curr Psychiatry. Rev. 2010;6:1-10.
3. Kirsch I, Sapirstein G. Listening to Prozac but hearing placebo: a meta-analysis of antidepressant medication. Prev Treat. 1998;1(2).