Open-Label Placebo Treatment for Cancer-Related Fatigue: A Randomized-Controlled Clinical Trial

Abstract

The purpose of this 21-day assessor blinded, randomized-controlled trial was to compare an open-label placebo (OLP) to treatment as usual (TAU) for cancer survivors with fatigue. This was followed by an exploratory 21-day study in which TAU participants received OLPs while OLP participants in the main study were followed after discontinuing placebos. Cancer survivors (N = 74) who completed cancer treatment 6 months to 10 years prior to enrollment reporting at least moderate fatigue (i.e., ≥4 on a 0–10 scale) were randomized to OLP or TAU. Those randomized to OLP took 2 placebo pills twice a day for 21 days. Compared to those randomized to TAU, OLP participants reported a 29% improvement in fatigue severity (average difference in the mean change scores (MD) 12.47, 95% CI 3.32, 21.61; P = 0.008), medium effect (d = 0.63), and a 39% improvement in fatigue-disrupted quality of life (MD = 11.76, 95% CI 4.65, 18.86; P = 0.002), a large effect (d = 0.76). TAU participants who elected to try OLP for 21-days after the main study reported reductions in fatigue of a similar magnitude for fatigue severity and fatigue-disrupted quality of life (23% and 35%, respectively). OLP may reduce fatigue symptom severity and fatigue-related quality of life disruption in cancer survivors.

Placebos Without Deception: Outcomes, Mechanisms, and Ethics

“…This is counterintuitive since placebos supposedly work because people believe they do, but (presumably) knowing a treatment is a mere sugar pill makes it difficult to believe they will work. In spite of the lack of intuitive appeal, numerous studies have demonstrated that deception may not be needed to elicit placebo effects and have also demonstrated potential effectiveness at improving significant clinical outcomes in patients with irritable bowel syndrome (IBS) (Kaptchuk et al, 2010), chronic low back pain (Carvalho et al, 2016), depression (Park & Covi, 1965), attention-deficit hyperactivity disorder (ADHD) (Sandler, Glesne, & Geller, 2008), rhinitis (Schaefer, Harke, & Denke, 2016), and cancer-related fatigue (Hoenemeyer, Kaptchuk, Mehta, & Fontaine, 2018). …”

“…Importantly, all these trials are characterized by the lack of blinding that can be achieved by comparing open placebos vs hidden placebos and the comparison with the best available treatment to estimate the relevance of open placebo potential effectiveness. Recently, open label placebos have been tested in 74 cancer survivors in a 21-day assessor blinded, randomized-controlled trial that compared an open-label placebo to TAU for fatigue (Hoenemeyer et al, 2018). Two placebo pills taken twice induced a 29% improvement in fatigue severity, and a 39% improvement in fatigue-disrupted quality of life.…”

“…Two placebo pills taken twice induced a 29% improvement in fatigue severity, and a 39% improvement in fatigue-disrupted quality of life. Open label placebos were tested in 74 cancer survivors ( N =74) in a 21-day assessor blinded, randomized-controlled trial that compared an open-label placebo to TAU for fatigue (Hoenemeyer et al, 2018). Two placebo pills taken twice induced a 29% improvement in fatigue severity, and a 39% improvement in fatigue-disrupted quality of life (Table 1).…”

“…Often, the open-label placebos were delivered in addition to the TAUs and importantly with explicit positive suggestions (Carvalho et al, 2016; Hoenemeyer et al, 2018; Kaptchuk et al, 2010; Schaefer et al, 2016) proving a rationale (e.g., “Pavlovian conditioning”) and instilling some hope of improvement. The only study that lacked any positive framing and instruction sets had the smallest effect size (Kelley et al., 2012).…”

Placebos in the era of open‐label trials: An update for clinicians

“…Finally, a recent randomized blinded controlled trial compared the use of OLP to the standard therapy for 74 cancer survivors with chronic fatigue. OLP participants reported a 29% improvement in fatigue severity and a 39% improvement in fatigue‐disrupted quality of life compared to the standard of care . In a systematic review of the five aforementioned OLP trials, a positive effect of OLP groups was found compared to no‐treatment groups .…”