title: A systematic review found no consistent difference in effect between more and less intensive placebo interventions.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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; I(2) = 68%).
  
  
  CONCLUSIONS
  In the studies included in this review, more intense placebos were not consistently associated with larger effects than less intense placebos.
authors: Institute of General Practice, Klinikum rechts der Isar, Technische Universität München, Orleansstrasse 47, 81667 Munich, Germany. Electronic address: faessler@ethik.uzh.ch.
authors: Margrit
authors: M
authors: Fässler
authors: Institute of General Practice, Klinikum rechts der Isar, Technische Universität München, Orleansstrasse 47, 81667 Munich, Germany.
authors: Karin
authors: K
authors: Meissner
authors: School for Public Health and Primary Care (CAPHRI), Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
authors: Jos
authors: J
authors: Kleijnen
authors: Nordic Cochrane Centre, Rigshospitalet, 7811, Blegdamsvej 9, 2100 Copenhagen, Denmark.
authors: Asbjørn
authors: A
authors: Hróbjartsson
authors: Institute of General Practice, Klinikum rechts der Isar, Technische Universität München, Orleansstrasse 47, 81667 Munich, Germany.
authors: Klaus
authors: K
authors: Linde
mesh_terms: D006801:Humans; D015990:Placebo Effect; D010919:Placebos; D016032:Randomized Controlled Trials as Topic / Q000379:methods* / Q000706:statistics & numerical data*
chemical_list: D010919:Placebos
keywords: Placebo effect; Placebos; Randomized controlled trial; Systematic review; Therapy; Treatment outcome