Parkinson's Disease patients secretly treated with a placebo instead of their regular medication performed better when told they were receiving a more expensive version of the "drug," researchers reported Wednesday in an unprecedented study that involved real patients.

The research shows that the well-documented "placebo effect" -- actual symptom relief brought about by a sham treatment or medication -- can be enhanced by adding information about cost, according to the lead author of the study. It is the first time that concept has been demonstrated using people with a real illness, in this case Parkinson's, a progressive neurological disease that has no cure, according to an expert not involved in the study.

"The potentially large benefit of placebo, with or without price manipulations, is waiting to be untapped for patients with [Parkinson's Disease], as well as those with other neurologic and medical diseases," the authors wrote in a study published online Wednesday in the journal Neurology.

But deceiving actual patients in a research study raised ethical questions about violating the trust involved in a doctor-patient relationship. Most studies in which researchers conceal their true aims or other information from subjects are conducted with healthy volunteers. This one was subjected to a lengthy review  before it was allowed to proceed, and, in an editorial that accompanied the article, two other physicians wrote that "the authors do not mention whether there was any possible effect (reduction) on trust in doctors or on willingness to engage in future clinical research."

Nor would such a ruse be allowed in clinical practice, said Ted J. Kaptchuk, director of the Program in Placebo Studies and Therapeutic Encounter at Harvard Medical School.  "I don't think it has a direct practical application," Kaptchuk said. "Telling people something is expensive, that's deception. That's not allowed in clinical practice."

Nevertheless, he said, the research is "provocative" and adds to the body of proof about how the placebo effect augments treatment of disease, especially when medication is provided. While most people think of a placebo as a sugar pill that replaces a real medication, the impact more commonly comes from "the engagement between patients and clinicians," in particular the way doctors create expectations that their efforts will help, Kaptchuk said. That includes a good relationship between doctor and patient; certain medical rituals, such as taking blood pressure and a medical history; and the "color, shape, number and cost" of the placebo drug, according to the institute's Web site.

In a 2008 survey of internists and rheumatologists, half said they regularly prescribed placebo treatments, and 62 percent agreed they are ethically permissible. Only two percent acknowledged using sugar pills, but 41 percent said they prescribed over-the-counter painkillers, and 38 percent said they prescribed vitamins.

In the study released Wednesday, 12 Parkinson's patients were told they were receiving injections of a new drug to help their brains produce dopamine, the neurotransmitter deficient in Parkinson's patients, instead of their regular drug, levodopa. They were told that one injection was a $1,500 version of the drug and another was a $100 version. In fact, they were given common saline both times.

The researchers found that the patients performed better on motor skills tests when they believed they were on the expensive drug, an effect that increased when they were given the expensive placebo first. Neither placebo was quite as good as levodopa, but the expensive version came close. There was no follow-up to determine how long the improvements lasted because the patients were put back on their regular drug regimens.

"I attribute this to patients' perception of greater quality intervention when cost is higher than what they would have been accustomed to," said Alberto Espay, director of the Gardner Center for Parkinson's Disease and Movement Disorders at the University of Cincinnati, who led the study.

When the researchers looked at functional MRI tests of the participants' brains, however, they found that the cheap placebo activated certain areas more than the expensive one, a result they did not expect. Espay suggested that patients might have been trying harder when they believed they were on a less costly medication.

The study noted that "our findings complement the well-known patient preference of brand name over generic, as recently confirmed in a study of similar design to ours."

Espay said the challenge now is to "harness" the knowledge in patient care. Because outright deception is ethically impermissible, other ways of enhancing the effectiveness of medication should be explored, he said.

"There is a lot that we can explain to patients about the benefits of medication that will enhance the benefit that they will get from them," Espay said.

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