Anti-inflammatory treatment helps ease anhedonia, depressive symptoms

Anti-inflammatory treatments appear useful in improving depressive symptoms and anhedonia in patients with depression who exhibit an inflammatory phenotype, results of a systematic review and meta-analysis have shown.

“The findings highlight the continued relevance of inflammatory physiology as a potential cause of depression as well as a treatment target, as conceived within a precision medicine approach,” said the researchers, who searched the databases of Medline, Embase, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and PsycINFO were searched in February 2025.

Randomized controlled trials (RCTs) of pharmacological anti-inflammatory treatment were identified. Those that examined anhedonia or depressive symptom severity and recruited individuals with depression who have an inflammatory phenotype or measured baseline inflammatory biomarkers that enabled a post hoc analysis were included in the meta-analysis.

Anti-inflammatory treatments reduced both anhedonia (Hedges’ g, 0.40, 95 percent confidence interval [CI], 0.08‒0.71) and depressive symptoms (Hedges’ g, 0.35, 95 percent CI, 0.05‒0.64) in RCTs that used an established cutoff for elevated inflammation (C-reactive protein ≥2 mg/L). [Am J Psychiatry 2026;doi:10.1176/appi.ajp.20241115]

However, treatment response (relative risk [RR], 1.28, 95 percent CI, 0.997‒1.64) or remission rates (RR, 1.18, 95 percent CI, 0.71‒1.95) did not differ. Furthermore, these results were consistent across clinical, interventional, or demographic characteristics.

Heterogeneity

The beneficial effects of anti-inflammatory treatment on symptoms of anhedonia and depressive symptom severity in depression are consistent with the results of previous RCTs in patients with unipolar or bipolar depression. [https://clinicaltrials.gov/ct2/show/NCT02473289; Brain Behav Immun 2020;88:631-639]

“However, it is important to note that there was considerable heterogeneity in the effect of anti-inflammatory treatment on depressive symptom severity,” the researchers said.

“Indeed, the three largest studies reported very small effect sizes (Cohen’s d<0.12), and the observed effect size for depressive symptom severity was driven by a modest number of small-sample RCTs,” they added. [Mol Psychiatry 2025;30:1407-1417; J Neurochem 2024;168:1817-1825]

On the other hand, anti-inflammatory treatment effects on anhedonia were “larger and … more consistent” relative to overall depressive symptoms.

“A specific effect of anti-inflammatory treatment on anhedonia is consistent with data from animal and human studies across a range of modalities and research designs demonstrating the sensitivity of reward circuitry to peripheral pro-inflammatory immune signalling,” the researchers said. [Pharmacol Rev 2021;73:1084-1117; Neuropsychopharmacology 2017;42:216-241]

Overall, the findings of this systematic review suggest the positive effects of anti-inflammatory treatment in improving depressive symptoms and anhedonia among patients with an inflammatory phenotype. The study also highlights the importance of considering a precision medicine approach that targets depressive symptoms, according to the researchers. [Mol Psychiatry 2022;27:1667-1675]

“A better understanding of the requisite dosage and duration of a specific medication that will meaningfully reduce levels of systemic inflammation and exert antidepressant effects is a prerequisite to their integration in clinical practice,” they added.

Depression, the chief cause of mental health-related disease burden worldwide, affects approximately 400 million individuals and accounts for nearly half (40 percent) of total days lost to poor mental health. [JAMA 2017;317:1517; Lancet 2012;379:1367-1368]