Editorial Note: I was asked to review Peter Kramer’s Ordinarily Well: The Case for Antidepressants for ISIS. The in print review is HERE. There is a sister post on RxISK – with a better cartoon and where the word Venomagnosia s explained – Come Back When you Have a Medical Degree.
This book was very difficult to review. In Ordinarily Well: The Case for Antidepressants, Dr. Peter Kramer makes two arguments that I agree with. One is that clinical observation—the interaction by which a medical professional learns about a patient—counts for something. The other is that clinical trials, or evidence-based medicine more generally, are not a replacement for clinical wisdom. He values antidepressants, in particular the selective serotonin reuptake inhibitor (SSRI) class of drugs, and so do I.
Applying support for clinical observation and skepticism about controlled trials to the question of whether antidepressants work, Kramer concludes that these treatments work very well. En route, he focuses on the claims of psychologist Irving Kirsch, among others, that based on clinical trial data, the benefits of antidepressants are all in the mind—a placebo effect. Kramer makes a straw man of Kirsch, but I agree with Kramer that antidepressants do things that are not all in the mind. I too reject Kirsch’s arguments that most of what antidepressants do stems from a placebo effect.
So where did my difficulties in reviewing the book come from? The trouble for me is that Kramer’s clinical vision seems strangely rose-tinted. He is an advocate of using antidepressants to treat depression, but he doesn’t seem to see any of the problems antidepressants cause. The fact that over half of the patients put on them don’t take them beyond a month should be telling. For those who do stay on treatment, he claims, no one has difficulties going off antidepressants with a gradual reduction in dosage. I, however, have patients suffering badly months or even a year later. In the case of any enduring problems, Kramer puts these down to the effects of the illness being treated rather than the medication.
There is no discussion in this book of significant problems that the use of antidepressants can cause. These include SSRI-induced alcoholism, SSRI-induced birth defects, including autism spectrum disorder, or permanent post-SSRI sexual dysfunction. In a 336-page book, the topic of SSRI-induced suicidality gets dealt with in one page. I think many surviving relatives would be astonished to hear that once the psychiatrist Martin Teicher had identified the problem of treatment-induced suicide, it became manageable. Kramer claims that “no case [he has had], not one, has looked like those Teicher has described, drug driven.”
Kramer asks us to believe in clinical observations—his observations. Not yours or mine or anyone’s that might cause the antidepressant bandwagon to wobble. He cites me at multiple points, so he is well aware of my work. But he doesn’t engage with the evidence that I and others have put forth, based on both clinical observations and other material, that SSRIs can unquestionably cause suicides and homicides, and do so to a greater extent than they prevent any of these events.
On the issue of children, suicide, and the black box warnings that antidepressants now carry, Kramer notes that “some of the data have trended the other way, although authoritative studies correlate increased prescribing with reduced adolescent suicide.” This fails to acknowledge that the drugs haven’t been shown to work in this age group. There is no mention that suicidal acts show a statistically significant increase in clinical trials in this age group. Kramer also does not indicate that among all ages, when all trials of antidepressants are analyzed together, they show increased rates of death (mainly from suicide) compared to non-treatment. He seems to have no feel for how compromised the “authorities” are that he uses to downplay the risks.
There are good grounds to be skeptical of the evidence-based medicine that Kramer uses to make his case. Quite aside from the fact that almost all the research literature produced by clinical trials is ghost written by pharmaceutical companies, and the data from them entirely inaccessible, controlled trials aren’t designed to show that drugs work. They work best when they debunk claims for efficacy, rather than the reverse. What’s more, the structure of clinical trials and their statistical analyses are the best method to hide a drug’s adverse effects. Ordinarily Well does not address these significant problems.
If a drug really works, then clinical observation should pick it up. We can tell antihypertensives lower blood pressure, hypoglycemics lower blood sugar, and antipsychotics tranquilize within the hour—all without trials. We can see right in front of us that antipsychotics badly agitate many people within the hour and that SSRIs can do so too. But we cannot see anyone get better on an antidepressant in a way that lets us as convincingly ascribe the effect to the drug. There is much to be said for clinical observation, but also a lot to wonder about when clinical trials suggest that drugs work but we can’t actually see it. For anyone keen to defend clinical observation, Kramer’s book poses real problems and would leave many figuring we need controlled trials instead.
I live and work in the United Kingdom and am acutely aware of some differences between America and Europe that also made it difficult to review this book. There is much more “bio-babble” in America than in Europe, from talk of lowered serotonin to chemical imbalances to neuroplasticity and early treatment preventing brain damage—all of which Kramer reproduces. I felt a John McEnroe “you cannot be serious” coming on at many points. The tone in which some of these points are made suggests that everyone reading them will find what is being said self-evident, when in fact it’s gobbledegook.
All medicines are poisons, and the clinical art is bringing good out of the use of a poison. It strikes me as un-American to even suggest that a drug might be a poison, and Kramer’s book gives no hint of this; the book is, in this sense, deeply non-clinical. He is giving an account of a mythical treatment, as far removed from real medicine as an inflatable sexual partner is from the real thing. It seems to me that he would not see or hear many of the patients I see, or at least would not credit their view of what is happening to them on treatment. This book will misinform anyone likely to take an antidepressant.
It will also cause problems for physicians. This book does not balance the risks and benefits that are intrinsic to medical wisdom. If antidepressants are as effective as Kramer claims, and are as free of problems as he suggests, there is no reason why nurses and pharmacists couldn’t prescribe them. Given that they are much less expensive prescribers, the surprise is that health insurers haven’t moved in this direction.
There is a way to bridge the gulf between Kramer and myself, which involves clinical observation. Most of the beneficial effects Kramer describes can be reframed in terms of an emotional blunting, or the numbing of all emotions, not simply the bad ones. Just like people on an SSRI will nearly universally report genital numbing within 30 minutes of taking their first SSRI—if they’re asked—people will also report some degree of emotional numbing—if asked. They don’t necessarily feel better; they simply feel less.
Unlike the somewhat mystical brain re-engineering Kramer invokes, this emotional blunting can be verified by clinical questioning. If clinical trials were designed to assess whether patients are numbed by these drugs, there would be little need for the fancy statistics that pharmaceutical companies use to claim the targeted benefits of their drugs, since emotional blunting would be evident through clinical questioning. And Irving Kirsch’s arguments about placebo would be irrelevant.
If SSRIs numb emotional experience, this would explain why they help some and not others, and explain the results we see in clinical trials, which are similar to the results that might be expected from a trial of alcohol versus placebo in the milder nervous states in which antidepressant trials have been run. This, then, would present us with a question: what do we think about emotional blunting as a therapeutic tool? Emotional blunting is not a romantic option. It’s a much more ordinary one. If that is the process by which antidepressants work, it does patients an enormous disservice to avoid discussing it entirely, which this book does.