Design: Updated systematic review and meta-analysis
Population: 24 studies of adults with major depression starting antidepressants
Primary outcome: Baseline peripheral inflammatory markers in responders vs non-responders
Effect: No marker significant in primary analysis; exploratory IL-6 in SSRI/SNRI studies SMD −0.37 (95% CI −0.69 to −0.05)

An update of a 2022 meta-analysis pooled 24 studies of adults with major depression whose inflammatory markers were measured before at least four weeks of antidepressant treatment, comparing responders with non-responders.

In the main pooled analysis, no baseline marker, including CRP and IL-8, separated responders from non-responders. Exploratory analyses of studies published since 2021 found lower IL-2 among responders, and lower IL-6 in those treated with SSRIs or SNRIs, but these were nominal findings with wide intervals, and the IL-6 result was sensitive to single studies.

The practical message is negative: there is no inflammatory blood test that tells you which patient will respond to an antidepressant. The subgroup signals are hypotheses for trials, not for clinic. It appeared in September 2026 and searched only PubMed for new studies.

Do not order CRP or cytokine panels to choose or predict response to an antidepressant.
Judge response clinically after an adequate dose and duration, as now.
Treat the IL-2 and IL-6 subgroup signals as research questions only.
Check for physical illness where inflammation is raised, but not to guide antidepressant choice.

Why it matters

It closes off, for now, a test some clinicians and patients hope will personalise treatment.

The statistics, in plain English

A standardised mean difference compares groups in units of spread; −0.37 is a small-to-moderate difference. The IL-6 and IL-2 findings came from exploratory subgroups with upper limits close to zero (−0.05 and −0.03), which is where chance findings usually sit. When many markers and subgroups are tested, some will cross p < 0.05 by chance alone.