Placebo -- As a Treatment -- Improves Cancer Fatigue

Nick Mulcahy

March 12, 2018

As a form of treatment, placebo pills may improve the common complaint of fatigue in cancer survivors, according to results from a first-of-its-kind study.

US researchers conducted a single-center, randomized clinical trial among 74 cancer patients with fatigue that compared treatment consisting of two placebo pills twice daily to treatment as usual (ie, educational materials).

The placebo pill intervention group (n = 39) reported statistically significant improvements in the two fatigue-related primary outcomes, symptom severity and disruption of quality of life, compared to the control group (n = 35) during a 21-day period, report the authors, led by Teri Hoenemeyer, PhD, director of education and supportive services, University of Alabama at Birmingham Comprehensive Cancer Center.

Specifically, compared to control patients, the placebo pill group reported a 29% improvement in fatigue severity (P = .008), which constituted a medium effect size, and a 39% improvement in fatigue-disrupted quality of life (P = .002), which represented a large effect size.

All of the participants had at least moderate (ie, clinically significant) fatigue, but most (62%) had severe fatigue. All were post treatment (range: 6 months to 10 years). Most were women (74%) and white (69%).

The study was published online February 9 in Scientific Reports.

The novel use of placebo in the new study differs from the standard use of placebo in clinical trials, Hoenemeyer told Medscape Medical News.

"Researchers will use a concealed placebo so that the participant thinks they are getting the drug/intervention. In our study, we actually told the participant that they were getting a placebo," she said. She added that the latter is called an open-label placebo.

This is the first open-label placebo study in a cancer population with a chronic adverse condition.

"The results are quite provocative," said N. Lynn Henry, MD, PhD, interim chief, Division of Oncology, Huntsman Cancer Institute, University of Utah, in Salt Lake City, who was not involved in the study.

The results are quite provocative. Dr N. Lynn Henry

"It will be interesting to see if open-label placebo is effective in other chronic conditions that cancer survivors face, such as neuropathy and aromatase inhibitor–associated arthralgias," she told Medscape Medical News.

For cancer fatigue, Henry primarily recommends increased activity levels and psychosocial or mind-body interventions. "I also discuss sleep hygiene and recommendations for addressing insomnia, especially if patients have hot flashes or other issues that disrupt sleep," she added.

Hoenemeyer said that modafinil (multiple brands), an activation drug commonly prescribed for cancer-related fatigue, is "moderately effective" but was not significantly better than a placebo in trials, and it has side effects, including difficulty sleeping. 

Henry could envision clinicians prescribing open-label placebo, if the evidence accumulates. But she acknowledged: "It will certainly require a change in mindset for providers."

Open-label placebo has been shown to be effective for other conditions, such as irritable bowel syndrome, episodic acute migraine attacks, chronic low back pain, allergic rhinitis, and depression, said both the study authors and Henry.

The idea of using a placebo as treatment should not shock clinicians, suggested Hoenemeyer.

"Many physicians use what we call 'impure' placebos in their medical practices," she said. Examples include the prescription of a vitamin supplement or antibiotic when no laboratory results indicate a need.

The American Medical Association states that medical use of placebos is ethical as long as physicians tell patients that the treatment is a placebo, said Hoenemeyer.

The power of placebo is still a mystery, she added: "Amazingly, while we may know about placebo effect, we do not understand it. As placebo researchers, we are still trying to untangle why placebos work."

Respectful Interactions

The study design called for all participants to meet with the principal investigator Hoenemeyer to discuss four points before randomization: (1) Powerful placebo effects have been found in some double-blinded clinical trials; (2) placebo responses may be attributed to conditioning, expectancy, and biological factors; (3) an open mind is helpful but is unrelated to outcomes; and (4) taking the placebo pills as prescribed for 21 days is important.

Hoenemeyer "tried to dispel widespread beliefs that placebo effects are negative or unauthentic."

Patients who expressed skepticism about placebo pills were told that their disbelief was "understandable," but they were encouraged to "see what happens."

After this talk, patients were handed an envelope that revealed their treatment group. At day 11, all patients received a check-in telephone call from cancer center staff. They returned to the clinic after completing the 21-day trial in order to complete study questionnaires on fatigue.

Respectful care from clinicians may enhance the placebo effect, say the authors.

Henry observed the same thing: "Much of the effect seems to be related to the patient-provider interaction."

The trial allowed the control persons to try the open-label placebo for 21 days after the main study concluded. A total of 34 of the 35 treatment-as-usual participants did so. That group reported similar reductions in fatigue severity and fatigue-disrupted quality of life (23% and 35%, respectively).

The authors and Dr Henry have disclosed no relevant financial relationships.

Sci Rep. Published online February, 2018. Full text

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