ANTI-INFLAMMATORY treatment reduced depressive symptom severity and anhedonia in individuals with depression and elevated inflammation, according to a new systematic review and meta-analysis of randomised controlled trials. The findings helped explain why earlier trials of inflammation-targeting therapies in depression have produced inconsistent results.
Anti-Inflammatory Treatment and Depression Outcomes
The preregistered analysis evaluated whether anti-inflammatory treatment for depression was effective specifically in patients with an inflammatory phenotype. Researchers pooled data from 11 randomised controlled trials that used established biomarkers of inflammation, most commonly C-reactive protein (CRP), with a threshold of ≥2 mg/L indicating heightened inflammatory status.
Across these trials, anti-inflammatory treatment significantly reduced anhedonia, defined as reduced capacity to experience pleasure, with a moderate effect size (Hedges’ g: 0.40; 95% confidence interval: 0.08–0.71). Depressive symptom severity was also reduced (Hedges’ g: 0.35; 95% confidence interval: 0.05–0.64). However, treatment response and remission rates did not differ significantly between treatment and placebo groups.
Depression is a heterogeneous condition, and growing evidence suggests that inflammation plays a causal role in a biologically distinct subgroup of patients. Elevated inflammatory markers such as CRP and interleukin-6 have been associated with poorer antidepressant response and more severe symptoms, particularly anhedonia.
Why Inflammatory Status Matters
Previous trials of anti-inflammatory treatment in depression have reported mixed findings, limiting clinical uptake. This meta-analysis demonstrated that failing to account for baseline inflammatory status likely diluted treatment effects in earlier studies. By focusing on patients with elevated inflammation, the analysis identified consistent symptom improvements regardless of demographic, clinical, or interventional characteristics.
The review included pharmacological anti-inflammatory agents across diverse mechanisms of action, supporting the broader concept of inflammation modulation rather than a single drug-specific effect. Importantly, no major safety concerns were identified in the analysed trials.
Clinical Implications and Future Directions
These findings suggested that anti-inflammatory treatment for depression could represent a precision-medicine strategy for a subset of patients with measurable inflammation. Routine assessment of inflammatory biomarkers may help guide treatment selection and improve outcomes.
However, the authors noted limitations, including relatively small trial numbers and short follow-up durations. Larger, longer-term studies are needed to determine whether symptom improvements translate into sustained remission and functional recovery.
Further research may also clarify which inflammatory markers best predict response, informing personalised approaches alongside existing antidepressant therapies.
Reference
Mac Giollabhui N et al. Effect of anti-inflammatory treatment on depressive symptom severity and anhedonia in depressed individuals with elevated inflammation: systematic review and meta-analysis of randomized controlled trials. Am J Psychiatry. 2026;183(1):70-9
