Placebo eff ects in psychiatry: mediators and moderators

Area of Science:

• Psychiatry
• Clinical Psychology
• Psychopharmacology

Background:

• The placebo response significantly impacts psychiatric clinical trials.
• Identifying reliable predictors of placebo response is crucial for treatment efficacy assessment.
• Previous research has explored various factors, including clinical and biological markers.

Purpose of the Study:

• To systematically review and synthesize findings on predictors of placebo response across diverse psychiatric disorders.
• To evaluate the success of meta-analyses, systematic reviews, and laboratory studies in identifying placebo response predictors.
• To determine the current state of knowledge regarding factors influencing placebo effects in psychiatry.

Main Methods:

• Conducted a comprehensive review of 31 meta-analyses and systematic reviews.
• Analyzed over 500 randomized placebo-controlled trials across multiple psychiatric conditions.
• Examined 20 potential predictors discussed in the literature, including trial design and patient characteristics.

Main Results:

• Only three factors were consistently associated with higher placebo responses: low baseline symptom severity, more recent trials, and unbalanced randomization (more participants assigned to active treatment).
• Randomized controlled trials of non-drug therapies did not yield additional predictors.
• Laboratory studies employing psychological, brain imaging, and genetic approaches failed to identify reliable predictors.

Conclusions:

• Predictors for placebo response in psychiatric disorders are not yet definitively established.
• The placebo response likely involves multiple mediators and distinct moderators.
• Further research is needed to uncover the underlying mechanisms and identify reliable predictors of placebo effects in psychiatry and beyond.