Effects of open-label placebos in clinical trials: a systematic review and meta-analysis

Abstract

Open-label placebos (OLPs) are placebos without deception in the sense that patients know that they are receiving a placebo. The objective of our study is to systematically review and analyze the effect of OLPs in comparison to no treatment in clinical trials. A systematic literature search was carried out in February 2020. Randomized controlled trials of any medical condition or mental disorder comparing OLPs to no treatment were included. Data extraction and risk of bias rating were independently assessed. 1246 records were screened and thirteen studies were included into the systematic review. Eleven trials were eligible for meta-analysis. These trials assessed effects of OLPs on back pain, cancer-related fatigue, attention deficit hyperactivity disorder, allergic rhinitis, major depression, irritable bowel syndrome and menopausal hot flushes. Risk of bias was moderate among all studies. We found a significant overall effect (standardized mean difference = 0.72, 95% Cl 0.39-1.05, p < 0.0001, I² = 76%) of OLP. Thus, OLPs appear to be a promising treatment in different conditions but the respective research is in its infancy. More research is needed, especially with respect to different medical and mental disorders and instructions accompanying the OLP administration as well as the role of expectations and mindsets.

Figure 1

PRISMA flow chart for study selection.

Figure 2

Within studies ‘risk of bias assessment for RCT on five ROB 2 criteria and overall. The risk of bias evaluation in the categories: bias arising from the randomization process (R), bias due to deviations from intended interventions (D), bias due to missing outcome data (Mi), bias in measurement of the outcome (Me), bias in selection of the reported result (S); overall risk of bias (O). Red symbols: high risk of bias; yellow symbols: some concerns; green symbols: low risk of bias.

Figure 3

Funnel plot of standardized between-group OLP vs. NT scores. Funnel plot of standardized mean difference (SMD) vs. standard error. The dotted lines indicate the triangular region within which 95% of studies are expected to lie in the absence of publication bias.

Figure 4

Forest plot for main outcome. Studies with open-label placebo (OLP) group and no treatment group were weighted using sample size (Total), means and standard deviations (SD). The means are shown by the green squares and the whiskers are representing the 95% confidence interval (CI). Overall standardized mean difference was calculated using the random effects model.