By Merritt McKinney

NEW YORK (Reuters Health) - A phenomenon called the "nocebo effect" may explain why some people report side effects that are not related to the medications they are taking, according to a new report.

  Most people have heard of the placebo effect, in which people on an inactive drug or therapy experience improvement in their symptoms. Researchers compare new drugs to placebo to gauge the true benefit of a therapy.

The placebo effect can make people feel better, but sometimes a dummy pill can have the opposite effect. Believing that they are taking an active medication, some patients develop side effects when taking a placebo.

This phenomenon is dubbed nocebo, which means "I will harm" in Latin. Placebo means "I will please" in Latin.

This nocebo effect may help explain why people taking real medications sometimes experience side effects that do not seem to be caused by the drug, according to Dr. Arthur J. Barsky and colleagues at Brigham and Women's Hospital in Boston, Massachusetts.

These so-called nonspecific side effects can have serious consequences, the researchers note in the February 6th issue of The Journal of the American Medical Association. Such side effects may cause patients to stop taking medications or physicians to discontinue effective drugs.

In a review of medical studies, Barsky's team identified several factors that seem to be related to the nocebo effect and nonspecific side effects of active medications.

The power of positive thinking may account for some of the placebo effect, but negative thinking has a power of its own, according to the researchers.

"Patients who expect distressing side effects before taking a medication are more likely to develop them," they state. The power of suggestion can be influential as well. In one clinical trial the authors reviewed, patients who had been warned of the possibility of gastrointestinal side effects of a medication were much more likely to experience such symptoms than those had not been told of the possible side effects.

Nonspecific side effects may be more common in people who have experienced side effects while taking medication in the past, the report indicates. Barsky and his colleagues also assert that patients with certain characteristics, such as anxiety and depression, may be more likely to experience nonspecific side effects.

What a person knows about a particular medication and even the color, name or shape of a pill may influence nonspecific side effects, the investigators note. One study found that more than 90% of people who had been classified as allergic to penicillin were able to take oral penicillin. It is possible, according to the authors, that some patients who were fearful of having a bad reaction to penicillin misinterpreted symptoms that were not caused by the drug.

In another study, patients taking blue placebo pills were more likely to report drowsiness than patients taking pink ones. The researchers point out that in one study, patients associated red, orange and yellow pills with stimulants and blue and green ones with sedatives.

In an interview with Reuters Health, Barsky said that there is little people can do to stop having symptoms. But it is useful for people to realize that "most of the time we have symptoms" of one type or another.

Most people feel drowsy, have a patch of dry skin or forget a phone number from time to time, but these symptoms may seem a much bigger deal during an illness, Barsky said.

When you get sick, "you begin to pay more attention to your body," he said. "You pick up on these things you would previously ignore" and attribute them to medications.

Before automatically blaming a symptom on a medication, Barsky advised people to think about whether they have had this symptom before and how often it occurred before jumping to the conclusion that it is a side effect of a drug.

SOURCE: The Journal of the American Medical Association 2002;287:622-627.