Debunking the power of the placebo effect.

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Oct. 23 2007 5:32 PM

Pill Popping

Debunking the power of the placebo effect.

Is there really a placebo effect?
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Is there really a placebo effect?

In a famous 1955 monograph in the Journal of the American Medical Association, Henry Beecher coined the term "powerful placebo." He used it to describe the miraculous improvement he said was seen in patients who thought they were getting medicine but really weren't. Beecher went so far as to say that this placebo effect accounted for precisely 35.2 percent of a treatment's results. And so he popularized the notion that patients could spontaneously heal—not only from psychological distress, but from physical disease—if they simply believed they were getting treatment.

Beecher's paper lay the foundation for the modern clinical trial, in which half of subjects take placebo pills or, sometimes, undergo sham procedures to fool them into thinking they are getting real treatment. Without this ritual, the thinking goes, the trials' outcomes would be skewed by the power of suggestion. In other words, scientists must give trial subjects placebos to distinguish the effect of taking active medication from the effect of taking a pill that you think will make you better, because you don't know it's only sugar.

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Beecher's paper is highly suspect. Half the studies he cited were his own, and his math was, frankly, misleading. Ted Kaptchuk, an associate professor at Harvard Medical School and former FDA expert panelist, dismisses the paper as a "polemical ploy," and other researchers have derided Beecher as "statistically naïve to the extreme." And yet Beecher's paper and the notion of a powerful placebo effect have escaped widespread scrutiny. For decades, mainstream medicine has uncritically promoted faith in the placebo effect—leaving behind reality-based science in the process.

As a result, some clinical trials go to extraordinary lengths to minimize the chances that positive thinking can cure all manner of illness and thus bias results. Consider the experience of George Doeschner, a New York electrician with Parkinson's disease, a condition caused by nerve degeneration in the midbrain. Doeschner flew to the University of Colorado in 1996, when he was 53, to enroll in an experiment to inject brain tissue salvaged from human fetuses into patients' brains, in hopes the cells would take up residence and restore neural function. Twenty patients would get the fetal cells; another 20 would just be a comparison group, receiving no treatment. But the researchers worried: If the injection group recovered, would that be because of the fetal cells pumping out dopamine, or was it possible that a patient's belief that the injections helped could explain his recovery of midbrain function? So, with the patients' consent, measures were taken to make them all think that they were getting treatment, even if they weren't.

On the day of his procedure, Doeschner was wheeled into the operating room and underwent an MRI scan to guide the neurosurgeon. Under local anesthesia—while he remained awake—the surgeon drilled four holes in his skull to expose the dura, or outmost membrane of the brain, for the fetal-cell injection. Then the surgeon stood outside Doeschner's field of view and did … nothing. Doeschner returned to the recovery room, having undergone a "sham surgery." Like all the subjects, he didn't find out for a year whether he'd really gotten the cells. (In the end, there was minimal difference in medical outcome between the treatment and sham group.) Fears of a strong placebo effect in this field were so strong that, according to lead researcher Dr. Curt Freed, the National Institutes of Health rejected a competing Yale Medical School study of fetal-cell injection because it lacked a sham-surgery group.

There are other similar trials: In the late 1990s, veterans enrolled in a Houston study of knee arthritis were assigned randomly to have either real knee surgery or a sham procedure, which consisted of being sedated, getting prepped in the operating room, having four superficial knee incisions, and hearing simulated splashing sounds. In 2005, 74 migraine sufferers in England had experimental devices snaked through a vein (subscription required) in their groin and implanted into the heart; 73 people in a sham group got the groin incisions without the device. More commonly, though, placebo trials involve dummy medication. Since 1962, the Food and Drug Administration has required all new drug approval trials—like those for high cholesterol, AIDS, cancer, and depression—to include a placebo group, where half the patients get inactive pills to create the false impression of therapy.

There's no question that placebos have psychological effects. The question is whether those effects really trigger healing on their own. For too long, medical science has accepted the magical thinking that patients' beliefs could activate dying neurons, heal knee cartilage, prevent air bubbles from traveling through the heart to cause migraines, lower bad cholesterol, and even cure cancer and AIDS. Like Beecher's original paper, a good deal of research about placebos is flawed. For example, a recent publicized Science study of brain scans purporting to show a placebo effect in Parkinson's disease included no objective measure of patients' symptoms and had no long-term follow-up.

Meanwhile, in a stunning 2001 article in the New England Journal of Medicine, two Danish physicians debunked the mighty placebo effect. Although most clinical trials include only active treatment and placebo groups, the researchers systematically collected all the studies in the medical literature (130 at the time) that also included a critical third group: patients who received neither active nor placebo treatment—just passive observation. The patients in placebo groups did report slightly less pain than the no-treatment groups; the analogy of a parent kissing a skinned knee comes to mind. But on almost every other objective measure of illness, the placebo-treated patients improved the same amount as the ones who got nothing at all. In other words, just believing you were getting treatment—the power of positive thinking—didn't really fix anything. It just made the patients hurt a little less.

The Danish authors sensibly pointed out that, like the Dow Jones industrial average, diseases' symptoms fluctuate up and down over time without clear explanations. For example, on 9/11, when Doeschner was stranded on the 34th floor of the World Trade Center when the jets hit, he had improved enough to run down the stairs and save himself despite his Parkinson's disease. Months afterward, his symptoms worsened without cause. It's these variations over time in clinical trials that get chalked up to the placebo effect. But according to the Danish review, these upswings and downturns are just the random course of illness, not the manifestations of a patient's psychic mojo.

If the belief in active treatment does little good, why not disclose to patients in clinical trials what treatment group they are in and spare them from sham surgeries and the empty ritual of taking a placebo pill? That's not likely. The decades-old belief in strong placebo effects has become a quasireligious idée fixe. Arthur Kleinman, the Harvard anthropologist who chaired an NIH forum on placebos in 2000, says the Danish study hasn't altered his faith that positive thinking can heal. Kaptchuk, for his part, suggests that a persistent belief in placebos is a misguided protest against cultural and personal insensitivity in modern medicine. It's also conceivable that some researchers fully understand the powerless nature of placebos—but realize patients are more likely to stay put in the no-treatment groups of clinical trials if they're convinced they're getting active medication.

For many people, the belief that one's mental state can heal is a comforting fantasy. But there's a dark side to wish-thinking that goes beyond pointless groin incisions, sugar pills, or drills to the cranium. If the only obstacle to perfect health is one's state of mind, then why not exhort the unfulfilled and the infirm to imagine their way to happiness and health, rather than work toward it or seek proven treatment? The door to quackery and exploitation yawns open close by.

Darshak Sanghavi, a pediatric cardiologist, is a fellow of the Brookings Institution and Slate’s health care columnist. Follow him on Twitter.

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