Medicinal mimicry; sometimes, placebos work—but how?

Science News, Feb 3, 2001 by Damaris Christensen

Simply participating in a medical-research trial sometimes improves a person's health. That's why investigators use placebos--inert pills or other dummy treatments--and make both study participants and staff unaware of whether a person is receiving an active treatment or not. Anywhere from 10 to 100 percent of the people taking placebos in trials see their symptoms wane. In such a test, a drug is considered to be beneficial only if it can beat the placebo.

Many studies suggest that problems like pain and depression respond particularly well to placebos. Blood pressure, cholesterol concentration in the blood, and heart rate are also affected by placebos, as are warts. On average, about a third of people taking placebos in studies report a benefit.

Researchers have typically measured this placebo effect for use in their statistical analyses, but recently they've become increasingly interested in understanding the effect. A conference last November at the National Institutes of Health in Bethesda, Md., highlighted that shift in attitude.

"The placebo effect has had a very pejorative meaning in the past. Instead of people trying to capitalize on it, they've discarded it," says meeting co-organizer Linda W. Engel of the NIH National Center for Complementary and Alternative Medicine in Bethesda, Md.

"Only since about 1960 have people really recognized the placebo effect as a phenomenon, and it has generally been seen as a hindrance," agrees Shepard Siegel of McMaster University in Hamilton, Ontario. "Only recently, as exemplified by the NIH conference, have people begun to look at [the placebo effect] as a potentially interesting effect," he adds.

Scientists at the conference reported findings suggesting that response to a placebo may rest on both the meaning that a person associates with a particular treatment and his or her previous experience with medication.

Placebos provide "an intriguing domain to ask broader questions about mind-brain relationships," says Arthur Kleinman of Harvard Medical School in Boston. Those issues include, he says, "how culture affects the success of treatment, why some diseases respond better to placebos than others, and how stress and mood affect biologic interactions in the body."

Some of the improvement seen among people taking placebos in drug trials may be spontaneous and reflect random fluctuations in their disease symptoms, says Kleinman. People participating in a trial may also be more likely to report positive results from whatever treatment they're given because they think that's what the researchers want to hear.

But other factors are at work, too. People getting placebos in clinical trials still get counseling about their disease and other care, says Daniel E. Moerman of the University of Michigan-Dearborn. "It's not like nothing happened to them," he says. "Words aren't inert."

Psychological studies have suggested that the "meaning" of a treatment matters, Moerman says. For example, people receiving a placebo that they're told is morphine report more pain relief than people given placebos masquerading as aspirin. Likewise, placebos that people think are brand-name aspirins reduce headache pain more effectively than placebos disguised as generic aspirin.

These studies show that people's perceptions of their treatment play an important role in healing, Moerman says. Few studies have compared active treatment with both placebo treatment and no treatment at all, he says. However, among the studies with such a design, most have shown that a group receiving a placebo is likely to improve faster than an untreated group, he says.

In the March 2000 MEDICAL ANTHROPOLOGY QUARTERLY, Moerman analyzed dozens of publications on ulcer, hypertension, and depression treatments.

He found that the strength of the placebo effect varied from country to country. For example, placebos were more effective in healing ulcers in Germany than in Brazil. However, Germans were less likely than their counterparts in other countries to benefit from placebos administered during trials of drugs to reduce high blood pressure. Participants in all the studies that Moerman reviewed were about equally likely to benefit from placebos administered in trials of antidepressants.

The findings are tentative and unexplained, says Ted J. Kaptchuk of Beth Israel Deaconess Medical Center in Boston, but they should be explored further. Some researchers have suggested that any treatment, active or not, works better when doctors tell the patient, "This is powerful medicine." For a physician to say that about a placebo, however, conflicts with the modern ethical mandates to always give patients the unvarnished truth, says Anne Harrington of Harvard University.

The placebo response is both a conscious response the meaning of therapy and a conditioned response to treatment from a health professional, some researchers contend. In other words, people not only think that a drug or procedure, will benefit them, but over time, they unconsciously associate the taking of medicine with relief.