A systematic review found no consistent difference in effect between more and less intensive placebo interventions

Abstract Objectives It has been suggested that some placebo interventions might be associated with larger clinical effects than others. In a systematic review, we investigated whether there is evidence from direct comparisons in randomized clinical trials including two or more placebo groups supporting this hypothesis. Study Design and Setting Eligible trials were identified through electronic database searches and citation tracking up to February 2013. Placebo interventions in a trial were categorized into a more intense and a less intense intervention based on complexity, invasiveness, or route of administration and time needed for application. Results Twelve studies with 1,059 patients receiving placebo met the eligibility criteria. Studies were highly heterogeneous regarding patients, interventions, outcomes, and risk of bias. Seven studies did not find any significant differences between the more intense and the less intense placebo intervention, four studies found differences for single outcomes, and one study consistently reported significantly larger effects of the more intense placebo. An explorative meta-analysis yielded a standardized mean difference -0.22 (95% confidence interval: -0.46, 0.02; P = 0.07; I² = 68%). Conclusion In the studies included in this review, more intense placebos were not consistently associated with larger effects than less intense placebos.