Confronted with a patient suffering from pain or a chronic disease for which no drugs are effective, doctors sometimes prescribe a sugar pill or vitamin. Although these "medications" have no active ingredients, patients often feel better. It's called the "placebo effect," and most scientists would say that it works only if the patient doesn't know the pill is fake. But a new clinical trial shows that patients can get better on a placebo even if they know the truth.
"It's a fascinating, innovative, and important study," says Klaus Linde, who studies complementary and alternative medicine at the Technical University in Munich, Germany.
Lead author Ted Kaptchuk of Harvard Medical School in Boston says he set up the trial in part because doctors seem to be struggling with the placebo problem. In a survey among 1200 internists and rheumatologists that Kaptchuk and others published in 2008, roughly half of participants admitted having prescribed placebos. Sometimes, these were truly inactive pills, but very often, they were "impure placebos": vitamins, over-the-counter pain killers, antibiotics, or even sedatives that the physicians believed had no specific action on the disease but might provide a placebo benefit.
Few were upfront with the patients about this, the study showed: Many described the treatment as "a medicine not typically used for your condition that might benefit you,” or words to that effect. That kind of mild deception is widely considered unethical, says Kaptchuk. It also may be unnecessary, according to the new study.
The team recruited 80 people with irritable bowel syndrome (IBS)—which includes symptoms like chronic abdominal pain, discomfort, and irregular bowel movements—for "a novel mind-body management study of IBS" in fliers and newspapers. All had a 15-minute conversation with a sympathetic doctor or nurse who told them that they would get either placebo pills or no pills at all. They were also told that placebos contain no active ingredient but can have a powerful effect because the body responds to them "like Pavlov's dogs" to a bell. The placebos—blue and maroon gelatin capsules—were given in a bottle labeled "placebo pills." There's no doubt whatsoever that patients realized they were inactive, Kaptchuk says: "They were told so many times, they had it coming out of their ears."
Three weeks later, those on the pills did significantly better on several scales of patient well-being often used in IBS drug trials. (The scales are all questionnaire-based because IBS severity is impossible to measure objectively.) On the so-called IBS Global Improvement Scale, for instance, in which patients rate improvement on a scale between 1 and 7, those who took the placebo scored an average of 5.0, compared with 3.9 in the control group, the researchers report today in the journal PLoS ONE. The difference is "huge," says Kaptchuk; in fact, it's comparable to the improvement seen in many trials of real drugs for IBS.
Kaptchuk says his team isn't advocating widespread use of placebos just yet. The group is trying to replicate the finding in studies with different diseases and a larger number of patients.
One potential weakness to the study, Linde says, is that because the outcome measure is so subjective, placebo patients may have exaggerated their improvement, for instance, to please the researchers. That's true, admits study co-author Irving Kirsch, a psychologist at the University of Hull in the United Kingdom—but in this type of study, it's simply impossible to eliminate this kind of bias, he says.
Trials in which placebos are used openly have been extremely rare, says Fabrizio Benedetti of the University of Turin in Italy. One such study was carried out in neurotic patients 45 years ago, but it had no control arm. The only other example is recent work in which placebos were used openly to treat attention deficit hyperactivity disorder (ADHD). Those studies showed that children could halve the dosage of their regular ADHD treatment without any negative consequences if a placebo was given at the same time.
"We're learning that it isn't useful to draw such rigid distinctions between mind and body," says James Bodfish of the University of North Carolina, Chapel Hill, one of the authors on the ADHD studies. "What we think of as physical disorders can be helped with psychological treatments and vice versa," he says. Patients and their parents "may not be wildly enthusiastic about taking placebos, but they're certainly open to it," says his co-author Adrian Sandler of the Mission Children's Hospital in Asheville, North Carolina.
Bodfish sees another potential weakness of the IBS study, however: The way it was advertised may have attracted patients who were more open and susceptible to getting better on placebos, which may have boosted the success of the placebo. "Interestingly, this weakness may also be a strength when viewed in another light," he adds. "In the context of 'personalized medicine,' it might make sense to selectively prescribe placebo treatment to only those patients most likely to derive benefit from it."
*The story has been amended to note the journal in which the study was published.