Differential placebo effect of sham acupuncture for chronic pain: a network meta-analysis of randomized controlled trials.

Background: The clinical effects of acupuncture are often underestimated due to the placebo effect of sham acupuncture. While multiple sham acupuncture methods have been used in clinical practice, it is challenging to select the appropriate sham acupuncture technique due to the lack of head-to-head trials.

Purpose: The purpose of this study was to compare the differential placebo effects of diverse sham acupuncture interventions, providing evidence-based guidance for selecting optimal placebo controls in clinical practice.

Method: PubMed, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science were systematically searched for randomized controlled trials comparing acupuncture with sham acupuncture for the treatment of chronic non-cancer pain (from inceptions to May 1, 2025). The primary outcome measure was pain variation, while secondary outcome measures included adverse events and the assessment of acupuncture blinding. Frequentist random-effect models were employed to perform indirect treatment comparison meta-analysis, and Confidence in Network Meta-Analysis (CINeMA) was utilized to evaluate the level of evidence.

Results: A total of 45 randomized controlled trials (RCTs) were included, involving 7 sham acupuncture methods and 8287 participants. Regarding pain variation, the difference was noted between the waiting treatment group (mean difference 1.86 (95% confidence interval 1.36 to 2.35), SUCRA 97.4%; moderate confidence of evidence) and manual acupuncture group was most pronounced, followed by the difference between the acupoint and no penetration group (mean difference 1.14 (95% confidence interval 0.74 to 1.55), SUCRA 73.6%; low confidence of evidence) and the nonacupoint and no penetration group (mean difference 1.00 (95% confidence interval 0.35 to 1.65), SUCRA 64.8%; low confidence of evidence). Additionally, the rate of adverse events was comparable among the aforementioned sham acupuncture groups, and the blinding procedure was successfully implemented in the trials.

Conclusions: The placebo effect of sham acupuncture is significant, among which the no penetration (acupoint or nonacupoint) groups exhibited the lowest placebo effect. Nevertheless, further head-to-head trials are warranted to obtain direct evidence.

Systematic review registration: PROSPERO no. CRD42024535012.