The Role of Inflammatory Markers as Predictors of Response to Antidepressants in Major Depressive Disorder: A Meta-Analysis.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of clinical studies
PubMed 42205644 · doi:10.7759/cureus.107728
What was done
A systematic review and random-effects meta-analysis (PRISMA 2020) searched PubMed/MEDLINE, EMBASE, Web of Science, Cochrane CENTRAL, and PsycINFO from January 1995 to December 2025. Studies were included if they evaluated adults with major depressive disorder (MDD) who had baseline inflammatory biomarkers measured prior to antidepressant treatment and reported response or remission. Pooled odds ratios (ORs) for nonresponse in patients with elevated versus normal inflammatory markers were calculated using DerSimonian-Laird random-effects models. Risk of bias was assessed with Cochrane RoB 2.0 and ROBINS-I tools.
What was found
Seventeen studies including 1,535 participants were analyzed. Elevated baseline inflammatory markers were significantly associated with higher odds of antidepressant nonresponse (pooled OR = 2.11, 95% CI: 1.84–2.43, p < 0.001, I² = 15%). Subgroup analysis indicated CRP, especially at thresholds around ≥3 mg/L, demonstrated the most consistent association (OR = 2.47, 95% CI: 1.96–3.11).
Why it matters
This meta-analysis demonstrates that baseline inflammation is correlated with worse clinical response to antidepressants in MDD. However, the findings are associative and do not yet support using inflammatory biomarkers to guide clinical treatment decisions.
Limits
Definitions and thresholds for elevated inflammation varied substantially across the included studies. Major confounding factors such as obesity, smoking, and metabolic comorbidities were not consistently controlled. The analysis pooled randomized and observational studies, and no prospective biomarker-guided treatment trials were identified.