This systematic review and meta-analysis aimed to quantify the magnitude of placebo and nocebo effects in pharmacological trials for OCRDs and identify clinical and methodological moderators influencing these effects.

A comprehensive literature search was conducted across multiple databases and clinical trial registries up to May 2025. Randomized, placebo-controlled trials involving pharmacological interventions for OCRDs were included. The primary outcomes were placebo effect size and placebo response rate; secondary outcomes included nocebo response rate and side effect profile. Data were extracted independently and meta-analysed using random-effects models. Meta-regression was performed to assess moderators of placebo response.

Fifteen eligible trials (N = 640; placebo N = 341) were included. The pooled placebo effect size was moderate (SMC = -0.63; 95% CI -0.77 to -0.48), with low heterogeneity (I2 = 4.73%). The placebo response rate was 21%, and the nocebo response rate was 18%. Despite testing a broad range of potential moderators, including clinical characteristics, methodological design, and medication class, no significant predictors of placebo effect size were identified. Side effects were reported in nearly one-third of placebo recipients, underscoring the relevance of nocebo effects.

Placebo and nocebo responses are noteworthy in trials for OCRDs and may influence perceived treatment efficacy. Variability in placebo responses is not well explained by currently measurable moderators. Further research is needed to explore neurobiological, psychological, and methodological contributors to expectancy effects in OCRD pharmacotherapy trials.