Summary: New analysis indicates that anti-inflammatory medications can reduce symptoms in a specific group of people with depression who also have persistent, low-grade inflammation. By reviewing randomized controlled trials that enrolled participants with elevated inflammatory markers, researchers found that anti-inflammatory treatments produced significant reductions in overall depressive symptoms and in anhedonia (reduced ability to experience pleasure).
These results point to a biological subtype of depression driven in part by immune dysregulation and suggest a route to more personalized treatment strategies. Future research will focus on identifying reliable biomarkers to predict treatment response and on developing safer, targeted anti-inflammatory therapies.
Key Facts
- Inflammation-linked depression: Anti-inflammatory drugs reduced the severity of depression among people who had measurable, chronic inflammation.
- Reduced anhedonia: Treatments also improved anhedonia, indicating effects beyond mood alone.
- Distinct subtype: Findings support an immune-related subtype of depression that may respond to tailored anti-inflammatory approaches.
Source: Mass General
Naoise Mac Giollabhui, PhD, Department of Psychiatry at Mass General Brigham, is the lead author of a paper published in American Journal of Psychiatry, titled “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.” Richard Liu, PhD, Department of Psychiatry at Mass General Brigham, is the senior author.
Q: How would you summarize your study for a lay audience?
Depression affects more than 400 million people worldwide at any time, and many do not benefit from existing antidepressant options. Over the past two decades, growing evidence has shown that a subset of people with depression experience chronic, low-grade inflammation that may contribute to their symptoms.
That observation prompted clinical trials testing various anti-inflammatory treatments in depressed patients, but results were inconsistent. We suspected these mixed findings stemmed from treating broad groups rather than focusing on those with measurable inflammation—if inflammation is absent, anti-inflammatory drugs are unlikely to help.
Our study set out to determine whether anti-inflammatory medications are effective when given specifically to depressed individuals who show evidence of chronic, low-grade inflammation.
Q: What question were you investigating?
We asked whether anti-inflammatory treatments reduce overall depressive symptom severity and anhedonia in depressed individuals who exhibit an inflammatory phenotype—meaning they have elevated inflammatory markers.
Q: What methods or approach did you use?
We performed a preregistered systematic review and meta-analysis of randomized controlled trials that enrolled depressed participants with evidence of inflammation or provided biomarker data permitting subgroup analyses. Trials included pharmacological anti-inflammatory agents and reported outcomes for depressive symptom severity or anhedonia. Multiple databases were searched, and independent reviewers screened studies, extracted data, and resolved discrepancies by consensus.
Q: What did you find?
We identified up to 11 randomized controlled trials including a total of as many as 321 depressed individuals with elevated inflammation. Across these trials, anti-inflammatory treatments significantly reduced both depressive symptom severity and anhedonia at study endpoints compared with placebo.
Q: What are the implications?
The findings support the existence of a depression subtype characterized by immune dysregulation that may respond to anti-inflammatory medications and to lifestyle interventions that lower inflammation. Recognizing and measuring inflammatory status could help clinicians match treatments to the patients most likely to benefit.
Q: What are the next steps?
Future work should develop and validate immune biomarkers that reliably predict which patients will respond to anti-inflammatory interventions, and it should refine therapies that selectively target harmful inflammatory pathways. Some potent anti-inflammatory medications carry serious side effects today, so safer and more targeted options will be necessary for routine clinical use.
Authorship: In addition to Mac Giollabhui and Liu, Mass General Brigham authors include Melis Lydston.
Funding: This research was supported by grants from the National Institute of Mental Health (K23MH132893, NMG; R01 MH115905, RTL; R01 MH124899, RTL; R21 MH130767, RTL; R01MH137793, RTL; K24 MH136418, RTL), a L.I.F.E. Foundation Research Grant (NMG), Harvard University’s Mind Brain Behavior Interfaculty Initiative (NMG), and Massachusetts General Hospital Translational Clinical Research Center’s Early Career Investigator award (NMG).
Disclosures: Richard T. Liu is a consultant for Relmada Therapeutics. Andrew H. Miller consults for Cerevel Therapeutics, Sirtsei Pharmaceuticals Inc., and Freedom Biosciences. Naoise Mac Giollabhui consults for Boehringer Ingelheim. No other authors reported disclosures.
Key Questions Answered:
A: People with depression who also show biological signs of chronic, low-grade inflammation—measured by elevated inflammatory markers—appear most likely to benefit. The study found that focusing on this subgroup yields the clearest therapeutic effects.
A: No. The evidence suggests benefit mainly when inflammation is present. In people without immune dysregulation, anti-inflammatory drugs did not show symptom reduction, underscoring the importance of personalized treatment selection.
A: The analysis included a range of pharmacological approaches, from agents that directly reduce inflammation to drugs that modulate immune signaling. Despite differences in mechanisms, the overall pattern showed symptom improvement in patients with elevated inflammation.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The journal article was reviewed in full by our editorial team.
- Additional explanatory context was added by staff to clarify the findings.
About this psychopharmacology and depression research news
Author: Cassandra Falone
Source: Mass General
Contact: Cassandra Falone – Mass General
Image: Image credited to Neuroscience News
Original Research: Closed access.
“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” by Naoise Mac Giollabhui et al., American Journal of Psychiatry.
Abstract
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
Objective:
Results from trials testing anti-inflammatory treatments for depression have been mixed. In this preregistered systematic review and meta-analysis, the authors examined whether anti-inflammatory interventions versus placebo reduce anhedonia and overall depressive symptom severity in depressed people who exhibit an inflammatory phenotype.
Methods:
Included studies were randomized controlled trials of pharmacological anti-inflammatory treatments that reported outcomes on anhedonia or depressive symptom severity and that either recruited participants with an inflammatory phenotype or provided baseline biomarker data enabling subgroup analysis. Searches were conducted in February 2025 across MEDLINE, Embase, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and PsycINFO. Multiple reviewers independently applied eligibility criteria, and two reviewers independently extracted and cross-checked data.
Results:
In randomized controlled trials (k=11) using a common cutoff for elevated inflammation (C-reactive protein ≥2 mg/L), anti-inflammatory treatment produced reductions in anhedonia (Hedges’ g = 0.40, 95% CI = 0.08 to 0.71) and in depressive symptoms (Hedges’ g = 0.35, 95% CI = 0.05 to 0.64). No significant differences were observed in treatment response rates (relative risk = 1.28, 95% CI = 0.997 to 1.64) or remission rates (relative risk = 1.18, 95% CI = 0.71 to 1.95). Effects did not vary meaningfully by clinical, intervention, or demographic factors reported in the trials.
Conclusions:
Anti-inflammatory treatments may be effective and safe for reducing depressive symptoms and anhedonia in depressed individuals with elevated inflammation. Prior inconsistent findings may reflect failure to account for patients’ inflammatory status when enrolling and analyzing clinical trials.