Factors associated with placebo response in depression trials: A systematic review of published meta-analyses (1990–2017)

Background:
Placebo response is common in patients with major depressive disorder (MDD) and decreases the likelihood of demonstrating drug superiority over placebo in a randomized, controlled trial (RCT). This paper aims to review the collective evidence for particular patient characteristics and trial features being associated
with placebo response in MDD.
Methods:
MEDLINE/PubMed publication database and Cochrane Library were searched for meta-analyses of placebo response in MDD, published in English from January 1990 to December 2017. The evidence for factors predicting a low or high placebo response was tabulated and weighted on the basis of methods, results, and quality of supporting studies.
Results:
We identified 58 papers, examining the possible association of 40 different factors with placebo response in MDD. Research methods varied considerably across articles so that our reporting remained descriptive. The evidence for any factor being associated with placebo response in MDD appeared very weak to weak.
Limitations:
Since none of the pooled analyses that we included could be regarded as a meta-analysis in its strict sense, and analytical approaches varied considerably, the current work is descriptive only, and without formal statistical analysis.
Conclusions:
Despite 25 years of pooling data from RCTs in MDD, there is no single factor for which strong evidence exists that it influences placebo response.