With his 1993 landmark book, “Listening to Prozac,” psychiatrist Peter D. Kramer became one of the most famous psychiatrists in America – second perhaps only to the fictional Frasier Crane of primetime TV. Since then, Dr. Kramer has continued to write – including a novel, books on other psychiatric topics, a blog, and articles for mainstream media, including the New York Times. In his latest book, “Ordinarily Well: The Case for Antidepressants,” Dr. Kramer will return to the role he left behind 23 years ago: defending the use of antidepressants.
Dr. Kramer notes that he doesn’t do this easily. In the preface, with a bit of dismay, he talks about how reviewers have called him “Dr. Prozac.” He’s felt stuck on a wave that didn’t reflect his diverse interests, and he didn’t want to be covered by the spreading stain of Big Pharma.
“Against all indications, I remained hopeful that I might walk free by day, alter my obituary,” Dr. Kramer tells the reader.
With “Ordinarily Well,” Peter Kramer is back as Dr. Prozac. The book is written as a response to the “research”– now seen so often in headlines – that antidepressants are as effective as sugar pills for mild to moderate depression, and they should be prescribed only for severe major depression. He gets even more specific: The book is written partly in response to an article by Dr. Marcia Angell , former editor in chief of the New England Journal of Medicine, published in June 2011 in the New York Review of Books, and Dr. Angell’s assertion that psychiatric medications are no more effective than placebo. Since psychotropics come with more side effects than placebos, the next logical conclusion is that they are not only ineffective – they are harmful.
As a clinical psychiatrist, I’ve found this evidence-based stance to be perplexing. People get better on antidepressants, even if you aren’t measuring Hamilton rating scores and even if you aren’t limiting treatment to those with severe major depression. I would estimate that at least some of the people, some of the time, get better, and when you progress to strategies of switching and augmenting, most of the the people, most of the time, get significant relief from their major depression.
Obviously, this is my clinical impression and not research, and Dr. Kramer takes a more ardent stance: Most patients with depression, be it mild, moderate, severe, or long-standing dysthymia, have a good response to antidepressants. It’s the minority who don’t respond.
Dr. Kramer goes through the “science” that would suggest that antidepressants are not effective for milder forms of depression, dysthymia, and neuroticism. He does a systematic and comprehensive review of how pharmaceutical studies are conducted, and what factors might skew results, and there is plenty here to fill the pages. He explains complex issues – such as meta-analyses and numbers needed to treat – such that the lay reader can follow.
As just one example, Dr. Kramer talks about screening research subjects for participation in antidepressant studies: “If raters have a sense of the minimum Hamilton score for admission to a study, and if they are under pressure to fill an enrollment quota, they will be inclined to tack on questionable Hamilton points. The boost will not be uniform. There’s no need to raise rating in the very ill. Scores for least afflicted participants will be most inflated.
“When off-site raters, with no stake in the pace of enrollment, analyze tapes of admission interviews,” he continues, “they find patients to be much healthier than the on-site Hamilton scores suggest. According to off-site assessments, many patients admitted to drug studies simply are not depressed.”
Dr. Kramer methodically marches through problems with finding patients for the studies, shortcomings of the Hamilton rating scale , which gives suicidal ideation the same point as a somatic symptom; the bias some studies have of excluding people with severe depression; substance abuse, or comorbid disorders; and “the floor effect,” which underestimates efficacy in patients with fewer symptoms.
He follows subjects at an unnamed for-profit research center and praises the skills of everyone who comes in contact with the research subjects, including the friendly van driver who fetches patients from their homes.
In a chapter titled “How We’re Doing,” Dr. Kramer goes into detail about specific studies, including the STAR*D trials , where patients were recruited from primary care and psychiatric clinics with the guarantee that they would be provided active medication, and those with comorbid conditions were not excluded.
“Only the sickest came. For nearly 80% of the participants (more than 2,800 were tested), the disorder was chronic. The average length of the current depressive episode was more than 2 years, generally despite attempts at treatment. The average enrollee had lived with depression on and off for more than15 years and was now in a seventh episode. Most patients were alcoholics or had other forms of mental illness.
“In the first phase, patients were put on Celexa [citalopram], managed by their own doctors. About 30% of patients achieved remission within weeks – with virtually no symptoms. Responses (including remissions) ran at just under 50%.
“Commentators considered this outcome disappointing, but is it?”
So this is Dr. Kramer’s strength: He writes an engaging book about a complex topic, arguing throughout that antidepressants work well and have been given a bum rap by flawed research and careless journalism that enjoy the sensationalism of villainizing psychotropics. There are no headlines, he points out, singing the praises of antidepressants for milder forms of depression, even when the evidence is there. Despite the complexity of the topic and the breadth of his research reviews, Dr. Kramer tells the story of antidepressant research in a way that a lay reader can follow. There are no mice or moleculars, no genetic loci, and no explanations of cytochrome P450 metabolism, neurotransmission, or synaptic blockade. The complexities are explained without medical lingo and, in the end, he concludes what psychiatrists see every day: Antidepressants work. They work for the sickest of the sick, and they work for those who are suffering from less-severe forms of depression.
Dr. Kramer ends the book with a discussion of his own clinical experiences, which are not always in tune with what the “science” declares to be true. He cites studies that show that psychotherapy adds nothing to the treatment of depression, yet still, he treats his own patients with psychotherapy. He notes studies that show maximal efficacy when medications are used at high doses and continue for the long haul at these high doses, yet in his own practice, he sometimes uses lower doses and weans patients off medications. He does a wonderful job of pointing out the disconnect of the promise of evidence-based medicine and how its usefulness has limits in clinical practice.
In our communications, Dr. Kramer wrote to me: “There were many reasons not to write this book, and I was reluctant. I took up the topic only after declining a series of opportunities to weigh in. This book is the only one of mine that I wrote primarily out of a sense of duty. The debunking of antidepressants had gone too far and been too widely accepted, and I believed that the underlying research was shaky.”
He worried that I saw his view of antidepressants as more favorable than he intended it to be, and in fact, his perception is correct: While I prescribe antidepressants and see their benefits (as well as their side effects) with many of my patients, I believe Peter Kramer is more enthusiastic than I am about the efficacy of antidepressants for milder forms of depression, dysthymia, and neuroticism.
“My view is the one expressed in the title,” Dr. Kramer countered, “Our medications work ordinarily well, and they bring patients to a state of ordinary wellness.”
Dr. Miller is a coauthor of “Shrink Rap: Three Psychiatrists Explain Their Work” (Baltimore: Johns Hopkins University Press, 2011).