A new study led by Naoise Mac Giollabhui, PhD, and senior author Richard Liu, PhD, from the Department of Psychiatry at Mass General Brigham, reports that targeting inflammation may help reduce depression severity and anhedonia. The findings were published in the American Journal of Psychiatry.
Mac Giollabhui explains that more than 400 million people worldwide are living with depression, and many do not respond to existing antidepressants. Growing evidence over the past two decades suggests that a subset of patients experience chronic, low-grade inflammation that may contribute to their symptoms. This has prompted clinical trials exploring whether anti-inflammatory treatments could help. However, past results have been inconsistent.
The research team suspected those mixed findings occurred because many trials did not focus specifically on patients with measurable immune dysfunction. “If there is no inflammation to begin with, anti-inflammatory medication won’t be very helpful,” Mac Giollabhui said.
To examine this issue, the researchers conducted a systematic review and meta-analysis of randomized controlled trials involving depressed individuals with elevated inflammatory markers. Their analysis included 11 trials and up to 321 participants.
The results showed that anti-inflammatory treatments significantly reduced both overall depression severity and anhedonia by the end of the study periods.
According to the authors, the findings support the idea that there is a distinct subtype of depression linked to immune system dysregulation. This subgroup may benefit from targeted anti-inflammatory therapies or lifestyle interventions that address chronic inflammation.
The next challenge, they note, is developing reliable biomarkers to identify which patients will respond to these treatments. They also emphasize the need for safer and more precise anti-inflammatory options, as some existing medications carry notable side effects.
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