Research Spotlight: A Subset of Patients with Depression Could Benefit from Anti-Inflammatory Treatment

Naoise Mac Giollabhui, PhD, of the Department of Psychiatry at Mass General Brigham, is the lead author of a paper published in American Journal of Psychiatry, “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, of the Department of Psychiatry at Mass General Brigham, is the senior author.

Q: How would you summarize your study for a lay audience?

At any given moment in time, more than 400 million individuals worldwide are battling depression. The antidepressant treatments that we currently have don’t work for many and there is a real need for new, effective treatments.

Over the last 20 years, there has been increasing evidence that some depressed individuals have chronic, low-grade inflammation that might be driving their symptoms. This observation of a dysregulated immune system led to clinical trials in which depressed individuals were given a variety of anti-inflammatory treatments. The results of these clinical trials, however, were mixed.

We hypothesized that results may have been mixed because these trials did not target the subset of depressed individuals exhibiting immune dysfunction—if there is no inflammation to begin with, anti-inflammatory medication won’t be very helpful!

So, our study was designed to determine whether anti-inflammatory medications are effective when given to depressed individuals who are actively exhibiting chronic, low-grade inflammation.

Q: What question were you investigating?

We investigated whether anti-inflammatory medications are effective in reducing depressive symptom severity and anhedonia (decreased ability to feel pleasure) in a subset of depressed individuals with chronic, low-grade inflammation.

Q: What methods or approach did you use?

We conducted a systematic review and meta-analysis of all randomized controlled trials in which we could determine the effect of anti-inflammatory medication on depressive symptom severity and anhedonia in depressed individuals with elevated levels of inflammation.

Q: What did you find?

We identified up to 11 randomized controlled trials in which anti-inflammatory medications were administered in up to 321 depressed individuals with elevated levels of inflammation.

We found that anti-inflammatory medications significantly reduced both depressive symptom severity and anhedonia at the study endpoint. 

Q: What are the implications?

This suggests that there is a subtype of depression characterized by a dysregulated immune system that could be effectively treated using anti-inflammatory medications and lifestyle-based interventions.

Q: What are the next steps?

There’s a lot of work that needs to be done to develop immune biomarkers that more accurately identify who will benefit from anti-inflammatory treatment for depression and to develop treatment approaches that selectively target dysfunctional inflammatory physiology. At the moment, some of the more potent anti-inflammatory medications have serious side-effects that make them sub-optimal for use in a clinical setting.

Authorship: In addition to Mac Giollabhui and Liu, Mass General Brigham authors include Melis Lydston.

Paper cited: 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.” American Journal of Psychiatry. DOI: 10.1176/appi.ajp.20241115

Funding: This work 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's General Hospital Translational Clinical Research Center's Early Career Investigator (NMG).

Disclosures: Richard T. Liu is a consultant for Relmada Therapeutics. Andrew H. Miller is a consultant for Cerevel Therapeutics, Sirtsei Pharmaceuticals Inc., Freedom Biosciences. Naoise Mac Giollabhui is a consultant for Boehringer Ingelheim. No other authors have disclosures to report.