Predictors of successful anti-inflammatory drug trials in patients with schizophrenia: A meta-regression and critical commentary

•Anti-inflammatories have potential benefit in patients with schizophrenia.•This meta-analysis investigated potential predictors of successful trials.•Small sample size and geographic variation correlated with greater effect sizes.•Baseline variables, including inflammation, should be considered in future trial designs. Given evidence pointing toward a role for immune dysregulation in the pathogenesis of schizophrenia, anti-inflammatory agents are promising adjunctive treatments that have potential to support a causal relationship for inflammation and psychopathology and lead to novel treatments for individuals. Indeed, previous meta-analyses have demonstrated small-to-medium effect sizes (ES) in favor of various anti-inflammatory agents, though there is significant heterogeneity and challenges in the interpretation of this literature. Identifying predictors, including sociodemographic variables, trial duration, and/or symptoms themselves, of successful anti-inflammatory trials may help identify which patients who might benefit from these compounds. We performed a meta-regression analysis of 63 adjunctive anti-inflammatory trial arms (2232 patients randomized to adjunctive anti-inflammatory agents and 2207 patients randomized to placebo).Potential predictors of effect size estimates for changes in psychopathology scores from baseline to endpoint included geography, trial duration, sample size, age, sex, race, smoking, body mass index, illness duration, age of onset of psychosis, study quality score and psychopathology scores (total and subscale) at baseline. Geography (β = 0.31, p = 0.011), smaller sample size (β = 0.33, p = 0.009), and higher study quality score (β = 0.44, p