Effects of placebos without deception compared with no treatment: a systematic review and meta-analysis

Aim
Our aim was to address the clinical efficacy of open-label placebos compared with no treatment by systematic review, and meta-analysis where possible.

Methods
We searched the Cochrane Injuries Group's Specialised Register, The Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE(R) In-Process & Other NonIndexed Citations (OvidSP), EMBASE (OvidSP), and clinical trials registers and screened reference lists. We ran the most recent search on April 27 2015. All randomised controlled trials of any medical condition, which had both open-label placebo and no-treatment or treatment as usual groups were included. Two authors independently applied the selection criteria and extracted data. The risk of bias of included studies was assessed using the Cochrane criteria. We used random-effects model for meta-analysis.

Results
After removing duplicates we screened 348 publications, assessed 24 articles for eligibility and identified 5 trials (260 participants) that met our inclusion criteria. The clinical conditions were: irritable bowel syndrome (IBS), depression, allergic rhinitis, back pain and attention deficit hyperactivity disorder (ADHD). The overall risk of bias was moderate. All 5 trials were eligible for meta-analysis. We found a positive effect for non-deceptive placebos (standardized mean difference (SMD) 0.88, 95% CI 0.62 to 1.14, P<0.00001, I2= 1%).

Conclusions
Open-label placebos appear to have favorable clinical outcomes, compared to no treatment or no additional treatment. Caution is warranted when interpreting the results due to the limitations including the small number of trials and lack of blinding. Larger definitive trials are now warranted to explore the potential patient benefit of open-label placebos.