Placebo and Active Treatment Additivity in Placebo Analgesia: Research to Date and Future Directions

International Review of Neurobiology
Matthew J ColeshillBen Colagiuri

Abstract

Placebo analgesia is a robust experimental and clinical phenomenon. While our understanding of the mechanisms of placebo analgesia has developed rapidly, some central questions remain unanswered. Among the important questions is how placebo analgesia interacts with active analgesic effects. It is an assumption underlying double-blind randomized placebo-controlled trials (RCTs) that the true effect of a treatment can be determined by examining the effect of the active treatment arm and subtracting the response in the placebo group ("the assumption of additivity"). However, despite the importance of this assumption for the interpretation of RCTs, it has rarely been formally examined. This article reviews the assumption of additivity in placebo analgesia by examining studies employing factorial designs manipulating both the receipt of an active analgesic and instructions about the treatment being delivered. In reviewing the literature, we identified seven studies that allowed a test of additivity. Of these, four found evidence against additivity, while the remaining three studies found results consistent with additivity. While the limited available data are somewhat mixed, the evidence suggests that at least under some conditions ...Continue Reading

Citations

Sep 27, 2019·Clinical Pharmacology and Therapeutics·Rui-Sheng WangKathryn T Hall
Jun 22, 2021·Frontiers in Psychology·Iñigo R Arandia, Ezequiel A Di Paolo

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