A systematic review and meta analysis of open label placebo effects in chronic musculoskeletal pain

Abstract

Placebo effects have been linked to a range of clinical symptoms. Traditionally, it was believed that deception was necessary for placebos to work. However, emerging research shows that openly administered placebos can benefit patients with various medical conditions. This study aimed to analyze the effects of Open-Label Placebo (OLP) on physical function and pain in individuals with chronic musculoskeletal pain. We conducted, in August 2024, a systematic literature search in PubMed, Web of Science, PsycINFO, and EMBASE for RCTs comparing OLP with any other intervention or no treatment. The level of evidence was assessed with GRADE. The effects on physical function tests were analyzed descriptively, while patient-reported outcome measures (PROMs) on physical functioning and pain were synthesized using random-effects meta-analyses. Study quality was assessed using the revised Cochrane risk of bias tool, RoB2. From 1775 articles, seven RCTs with a total of 703 participants were included-five on back pain and two on knee pain. All seven studies had a high risk of bias for PROMs due to awareness of the intervention. Among the four studies that reported objective outcomes, two had a low risk of bias and two had some concerns. All studies included a follow-up between 3 and 12 weeks, except for one study that had a 3-year follow-up. With moderate evidence, we found that OLP as a stand-alone or add-on treatment had no effect on physical function tests, but concerning PROMs, there was low evidence for very small to moderate effects on self-reported physical function (SMD = 0.40, 95% CI 0.19-0.60) and small to moderate effects on pain intensity (SMD = 0.46, 95% CI 0.28-0.63) compared to treatment as usual or no treatment. These results suggest that OLP may enhance PROMs in chronic musculoskeletal pain patients, but one should keep in mind that the clinical value of OLP is not yet established. This study received no specific funding.Registered in PROSPERO: CRD42023487578.

Keywords: Back pain; Knee pain; Literature review; Long-lasting pain; Nonspecific pain; Placebo.

Fig. 1

PRISMA flow chart.

Fig. 2

Descriptive analysis for tests of physical function. OLP∆, Change in OLP group; Control∆, Change in control group; g, Hedge’s g; Direction 0, indicates no effect favoring either OLP or the control group.

Fig. 3

Forest plots for PROMs of physical function and pain.

Fig. 4

Sensitivity and subgroup analyses—only studies on back pain.

Fig. 5

Sensitivity and subgroup analyses—only studies on knee pain.