In patients with chronic low back pain (cLBP), the addition of open-label placebo to treatment-as-usual (TAU) resulted in greater pain reduction in patients than the use of TAU alone, according to results from a randomized controlled trial published online October 13 in Pain.1
Cláudia Carvalho, PhD of Lisbon’s Instituto Universitário de Ciências Psicológicas and colleagues sought to determine whether placebo analgesia in cLBP could be ethically elicited by providing disclosure to patients regarding the inert nature of the pills they were receiving.
Co-author Irving Kirsch, PhD, told Clinical Pain Advisor that the ability of placebo to modulate pain is well-established, but the presumption that deception is necessary has presented a barrier to placebo use.
“Our study shows that clinically significant placebo effects can be produced even when patients are told that they are being given placebos. This provides an ethical means of harnessing the placebo effect in clinical practice,” he stated. Dr Kirsch is Associate Director of the Program in Placebo Studies and lecturer in medicine at the Harvard Medical School and Beth Israel Deaconess Medical Center.
High Yield Data Summary
- Open-label placebo presented in a positive context was found to be associated with decreases in back-related dysfunction, assessed on the Roland-Morris Disability Questionnaire, and pain scores in patients with chronic low back pain
Dr Carvalho and colleagues conducted the study in 97 patients recruited through advertisements for “a novel mind–body clinical study of chronic low back pain.” Patients were randomized to receive placebo plus TAU or TAU alone.
After providing informed consent, patients from both study arms were advised of 4 “discussion points”: that the placebo effect can be powerful; that similar to Pavlov’s dogs who salivated at the sound of a bell, the body automatically can respond to placebo; that a positive attitude can be helpful but is not necessary; and that adherence to the pill-taking regimen was critical.
These instructions were provided in concordance with the prevailing theory that placebo effects constitute a learned response. Expectations and beliefs may affect central nervous system mechanisms, thus influencing behavioral and clinical outcomes.2
Following the 3-week treatment period, patients in the placebo arm experienced a 30% reduction in both usual and maximum pain vs reductions of 9% and 16% in usual and maximum pain among patients in the TAU arm, respectively.
Minimum pain dropped by 16% among placebo-receiving patients but increased by 25% in patients receiving only TAU. Pain-related disability was reduced by 29% in the placebo arm compared to 0.02% in the TAU arm.
Alain Braillon, MD, PhD, a public health expert who critiqued the use of placebo in The American Journal of Bioethics,3 expressed skepticism about the study’s results in an interview with Clinical Pain Advisor.
“The patients had to modify their habits and took carefully their orange gelatin capsules,” he noted. “This may have improved the compliance with the other treatments against pain and accordingly decreased pain. This should have been monitored. The design of this study was very poor. The authors expected a response and did not want to look for alternative solutions or bias.”
Summary and Clinical Applicability
“Our data suggest that harnessing placebo effects without deception is possible in the context of a plausible rationale. More research on this possibility is warranted in cLBP and other conditions defined by self-appraisal,” the investigators wrote in the article’s conclusion.
- Carvalho C, Caetano JM, Cunha L, Rebouta P, Kaptchuk TJ, Kirsch I. Open-label placebo treatment in chronic low back pain: a randomized controlled trial. Pain. 2016 Oct 13. doi:10.1097/j.pain.0000000000000700 [Epub ahead of print]
- Colloca L, Miller FG. How placebo responses are formed: a learning perspective. Philos Trans R Soc B Biol Sci. 2011;366(1572):1859-1869. doi:10.1098/rstb.2010.0398.
- Braillon A. Placebo is far from benign: it is disease-mongering. Am J Bioeth AJOB. 2009;9(12):36-38. doi:10.1080/15265160903234078.