Paracetamol and the placebo effect in osteoarthritis trials: a missing link?

This paper addresses the role of paracetamol in placebo-controlled osteoarthritis (OA) trials and the potential contribution to the large placebo response in such trials. Paracetamol is used as rescue medication in nearly all OA placebo-controlled trials. Triggered by the discussion about the placebo effect in general and because of the lack of systematic reviews of placebo effect in OA trials, a recent meta-analysis examined the placebo effect and its potential determinants in the treatment of OA, as the main result came out that placebo is very effective in the treatment of OA, especially for pain, stiffness, and self-reported function. However, mostly limited data are available from published OA trials on the starting dose, final dose, dose over time of paracetamol use, and the percentage of patients who used rescue medication during the study. Paracetamol may be an important additional simulated effect of placebo administration mimicking the true placebo effect and thus a missing link contributing partially to the large placebo response in OA trials. Therefore, the positive effect of paracetamol on symptom relief as well as the need for standardized recording of rescue medication should be taken into account when designing, executing, and interpreting placebo-controlled OA studies.