Walter Brown, a professor of psychiatry at Brown and Tufts, first caught my attention in the mid-1990s when I was researching my December 1996 Scientific American article "Why Freud Isn't Dead," on lack of progress in psychiatry. My research persuaded me that the placebo effect (which I have written about here and here) accounts for most if not all of the benefits of psychotherapy and drug treatments for depression. Brown provoked a furor among his colleagues by proposing that psychiatrists prescribe placebo pills for mildly and moderately depressed patients, a topic that he revisited in a 1998 article for Scientific American. He has delved even further into the implications of the placebo effect on psychiatry and other fields of medicine in his incisive new book The Placebo Effect in Clinical Practice (Oxford University Press), which I highly recommend. I recently interviewed Brown:

Horgan: What have we learned about the placebo effect since Henry Beecher's landmark 1955 work The Powerful Placebo?

Brown: Beecher’s paper put the placebo effect on the map, and his general proposition that the placebo effect is ubiquitous has withstood the test of time. He also proposed, among other things, that there is a constant placebo response across conditions. 35.2 % improve with placebo was the figure he came up with. But since then, thanks to thousands of placebo-controlled clinical trials, we have learned that some conditions are far more placebo responsive than others. Even among pain syndromes, which for the most part show robust placebo effects, there are differences: for example, post operative pain appears more placebo responsive then migraine headaches. About 40% of mildly to moderately depressed patients improve with placebo as opposed to only 10-20% of those with obsessive compulsive disorder. Irritable bowel syndrome is highly placebo responsive--about 40% improve with placebo--whereas only about 20% of people with chronic fatigue syndrome get better with placebo. (I cover these issues in my book’s chapter on variations).

Since Beecher, laboratory based and clinical studies have identified some of the mechanisms behind the placebo effect. Expectation is the most widely studied. Both rigorously designed and controlled laboratory studies and clinical studies as well show that what one anticipates from a treatment has a profound impact on what one does experience. In the past decade a number of studies have shown that when people get placebo but believe that they’re receiving a medication they undergo some of the same brain changes that occur with the active medicine. (I go into the details in the chapter on expectation). The effect of expectation on response to placebo and other treatments seems to rest on a fundamental psychobiologic process (whatever that means). In the past 60 years we’ve also learned about the role of conditioning in the placebo effect and--a special interest of mine--the role of certain elements of the treatment situation and doctor-patient relationship in bringing about placebo effects.

Horgan: Haven't clinical trials eliminated concerns that many modern medical treatments, when they work, are harnessing the placebo effect?

Brown: Although drugs need to demonstrate efficacy in controlled clinical trials in order to get FDA approval, many widely used treatments are not subjected to clinical trials, including psychotherapies, surgical procedures and all the alternative treatments. And once a drug gets FDA approval it can be used in a so-called “off-label” manner for any condition including those not studied in the clinical trials that led to approval. Most drugs are frequently used “off-label" for conditions in which their efficacy has not been carefully studied or studied at all. Even placebo-controlled trials are no guarantee that a drug that looks good is not deriving its benefit from the placebo effect; double blind clinical trials are not truly double blind. Even though they are designed to eliminate the bias that comes from knowledge about whether drug or placebo is on offer, almost invariably the investigators conducting the trial know, because of side effects, who’s getting what.

Placebo effects continue to be mistaken for treatment effects with troubling frequency. As just one example, vertebroplasty--injecting cement into a fractured vertebra--was widely used as a treatment for vertebral fracture from the early 1990s through the first decade of this century until a controlled trial showed that a sham (placebo) procedure (nothing injected) was equally effective in reducing pain and disability. (I discuss this particular study in the first chapter)

Horgan: Do you worry that raising the awareness of patients about the placebo will undermine patients' trust in modern medicine?

Brown: It may cause people to wonder if their improvement is “just” a placebo effect and if the treatment they’re getting is not “really” working. But I believe that most folks trust their own doctors--if not doctors in general--and will believe what their doctors tell them about a treatment’s inherent effectiveness.

Horgan: Why do you focus in your book so much on psychiatry?

Brown: My original concept for the book was to look at the placebo effect in mental health alone. But as I started to do the research and write it I decided to look at the placebo effect more generally and go beyond psychiatric illness to medicine in general. Some of the focus on psychiatry derives from the original impetus for the book. I also focus on psychiatry because my own research on the placebo effect has been in depressive illness, and the condition in which the placebo effect has been most studied is probably depression. A good bit of what we have learned about the placebo effect in depression sheds light on the placebo effect in other conditions. It’s also the case that a number of psychiatric conditions are highly placebo-responsive. Also psychotherapy has a lot in common with placebo treatment; the relationship between the two is a matter of controversy and I wanted to tackle that issue. And finally, although I believe that the placebo effect is pertinent to all illnesses and treatments, as a psychiatrist my expertise and interests lie primarily in psychiatry.

Horgan: What are the implications of the placebo effect for psychiatry? Given the side effects of many psychiatric drugs, should psychiatrists prescribe placebo treatments more often for mental disorders?

Brown: Given the high rates of improvement with placebo--close to the rates with drugs--in some psychiatric conditions such as mild to moderate depression and panic disorder--and the side effects and expense of drugs, I think it does make sense for psychiatrists to prescribe placebo treatments in some circumstances. The placebo could be a pure placebo—i.e., a sugar pill--or a nontoxic alternative therapy given to promote a placebo effect. I go into the details of how to go about this and the ethical and clinical implications in the last chapter. Of equal importance, psychiatrists like all health professionals should apply what is known about mobilizing the placebo to enhance the benefit of all treatments.

Horgan: Do you agree with Jerome Frank [a prominent investigator of the efficacy of psychotherapy] that psychotherapists, like shamans and faith healers, are just harnessing the placebo effect?

Brown: I wouldn’t say “just”; the placebo effect can be pretty powerful and harnessing it is not a trivial intervention. But I do agree with Jerome Frank that psychotherapists, shamans and faith healers accomplish what they do by providing the common factors of treatment--the presence of a healing authority, a healing ritual, expectation of recovery, etc.--that are also found with placebo treatment, that promote a placebo effect, and that are probably the active ingredients of all the psychotherapies.

Horgan: Have your writings about the placebo effect in psychiatry gotten you in trouble with other psychiatrists?

Brown: In 1994 the journal Neuropsychopharmacology published a paper in which I proposed that in some circumstances depression should be treated with placebo. The paper was followed by invited commentaries from three psychiatrists, two psychologists and one internist. All but the internist freaked out over the idea--it was irresponsible, unethical, dangerous, etc. I would guess that some psychiatrists will object to what I say about the commonalities between psychotherapy and placebo, and others will object to and have objected to my position on the similarity in outcome between placebo and drugs for mild to moderate depression. Oh well.