Some Placebos More Effective Than Others in Osteoarthritis


A review and meta-analysis of 149 randomized clinical trials of adults with knee osteoarthritis, shows that some placebos can trigger clinically relevant responses.

Many widely-used drugs for knee osteoarthritis have a treatment effect so small that randomized controlled trials contradict each other, contradict the clinical experience of many rheumatologists, and sometimes have difficulty distinguishing the drugs from placebos. Now, a review and meta-analysis of 149 randomized clinical trials of adults with knee osteoarthritis, shows that some placebos can trigger clinically relevant responses. The article appears in the July 27, 2015 online edition of the Annals of Internal Medicine. [[{"type":"media","view_mode":"media_crop","fid":"40098","attributes":{"alt":"","class":"media-image media-image-left","id":"media_crop_3218258847482","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"4065","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.0080003738403px; line-height: 1.538em; float: left;","title":" ","typeof":"foaf:Image"}}]]“Our study found significant differences among the effect sizes of different placebos administered to patients enrolled in knee osteoarthritis trials,” the authors wrote. Led by Raveendhara R. Bannuru, MD, of Tufts Medical Center, Boston, the authors of the review conducted a network meta-analysis comparing pharmaceutical treatments to the most commonly used placebo interventions for knee osteoarthritis–related pain, specifically, oral placebos in 46 trials, intra-articular placebo in 63 trials, topical placebo in nine trials, and a combined oral and topical placebo in three trials.


  • Placebos were more effective than many widely-used drugs
  • Injected and topical placebos were more effective than oral placebos
  • Injected placebo was more effective than acetaminophen, and topical placebo was equivalent to acetaminophen
  • Hyaluronic acid was effective in this network meta-analysis and in an earlier one

 They reported that intra-articular and topical placebo interventions were associated with greater responses than oral placebo. The pharmaceuticals featured in this review included, intra-articular hyaluronic acid, intra-articular corticosteroids, non-selective NSAIDs, topical NSAIDs, COX-2 – selective NSAIDs and acetaminophen. The authors were surprised to find that intra-articular placebo had an effect size substantially greater than that of acetaminophen, and that topical placebo had an effect size equivalent to acetaminophen. “Knowledge of these effects is important for designing new clinical trials and framing clinical practice guidelines and health care policy decisions,” the authors wrote. The mode of treatment delivery apparently has an impact on benefits observed in patients. The placebeo and contextual effects are an integral part of any treatment, write the authors of an editorial that accompanied the article. The authors of the editorial, of the University of Nottingham in the United Kingdom, write that "Bannuru and colleagues reaffirm that placebos are not equal and demonstrate that use of different placebos may affect determination of relative specific treatment efficacy in network meta-analyses." “Understandably, but regrettably, the emphasis in reporting of individual randomized, placebo-controlled trials has been on the difference between treatment and placebo. This focus detracts from the larger overall improvement that participants have from the treatment and the often impressive placebo effects,” the authors of the review wrote.


The study's lead author, Raveendhara R. Bannuru, MD, Tufts Medical Center, Boston, reports grants from the Agency for Healthcare Research and Quality and the American College of Rheumatology. The other authors also made a number of disclosures.



Bannuru RR, McAlindon TE, Sullivan MC, et al.

Effectiveness and Implications of Alternative Placebo Treatments: A Systematic Review and Network Meta-Analysis of Osteoarthritis Trials.

Annals of Internal Medicine.

Published online July 28, 2015. doi:10.7326/M15-0623  Zhang W, Zou K, and Michael Doherty M. Editorial, "

Placebos for Knee Osteoarthritis: Reaffirmation of “Needle Is Better Than Pill.”

Annals of Internal Medicine.

Published online July 28, 2015. doi:10.7326/M15-1580  

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