Latest study to show benefit of open-label, or “honest” placebos

Underscores role of mind-body connection in treatment

Patients who took a placebo for cancer-related fatigue experienced an improvement in their condition even when they were told up front that the pill was inert, with no active pharmacological ingredients, investigators at Dana-Farber Cancer Institute report in a new study.

The paper, published by the journal Supportive Care in Cancer, is the latest in a string of studies that have shown the potential benefits of open-label, or “honest,” placebos in patients with a variety of medical conditions. The results of these studies suggest that, contrary to the traditional notion that placebos’ benefits are purely a psychological phenomenon, the placebo effect may be rooted in the complex connection between mental and bodily processes.

“Cancer-related fatigue is one of the most common side effects of treatment, affecting up to 75 percent of patients at some point during treatment or survivorship,” said the study’s first author, Eric Zhou, PhD, of Dana-Farber. “Current treatments for this fatigue have limitations and can carry side effects of their own. Open-label placebos have been shown to be effective in patients with nausea, pain, inflammatory bowel syndrome, and migraine. The beauty of such placebos is that there are no side effects – only benefits at a very low cost.”

The use of placebos in medical research has usually meant keeping clinical trial participants in the dark about the treatment they’re receiving. Typically, participants are randomly assigned to receive either a study medication or a placebo, with neither the participants nor the researchers knowing who received which one until the study is closed and the results analyzed. To determine whether a study medication is truly effective, researchers look to see whether the patients who took it fared better than those who took the placebo.

In the new study, 40 cancer survivors were randomly grouped to receive a placebo – and explicitly told it was a placebo – or to a control group who did not receive anything. Eight and 22 days after beginning the trial, participants completed questionnaires designed to assess their level of cancer-related fatigue.

“We found that at both day 8 and 22, the group receiving the placebo reported significantly improved cancer-related fatigue, while the control group’s fatigue remained constant,” said Zhou.

Researchers also examined whether certain personality characteristics or a genetic variation in the body’s machinery for breaking down dopamine affected response to the placebo. They found such a connection with the genetic variation but not with personality type.

The finding of a link between placebo response and a specific genetic variation suggests that the placebo effect “is not entirely in one’s head, as it has often been portrayed, but has a real, physical component. Research on pain has taught us that our bodies respond to a placebo with physiological changes that mimic the action of opiates (pain-relieving medications). We don’t yet understand how placebo improves patients’ fatigue, but these genetic results suggest that some physiological change is involved,” said the study’s senior author, Christopher Recklitis, PhD, MPH, of Dana-Farber.

It is unclear why patients often respond positively to a placebo even when they know it has no biological effect. Some speculate it stems from an acquired physiological response to the physical act of swallowing a pill. “If someone has a history of taking medication and has been helped by it, the body and mind may learn that the process itself is significant,” said Recklitis. He likens it to the experience of taking an aspirin for pain and feeling an improvement within minutes, even though one knows it takes much longer for the aspirin to take effect.

The study findings reinforce notions of the mind’s ability to alter one’s perceptions of bodily ailments. “To undervalue the mind-body connection, and its potential role in treatment, is to miss an opportunity to help the patient,” Recklitis observed.

The co-authors of the study are Alexis Michaud, Jamie Blackman, RN, BSN OCN, and Ann Partridge, MD, MPH, of Dana-Farber, and Kathryn Hall, PhD, MPH, of Brigham and Women’s Hospital.

Funding for the study was provided by the Foundation for the Science of the Therapeutic Encounter.