What is it about?
This study investigates whether anti-inflammatory treatments improve symptoms of depression in depressed individuals with chronic inflammation. In this paper, we demonstrate that when individuals with an inflammatory phenotype (most commonly blood levels of C reactive protein > 2 or 3mg/L) are treated with anti-inflammatory agents, we observe a meaningful improvement in symptoms, particularly anhedonia.
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Why is it important?
Depression is the leading cause of disability worldwide, and most people do not find symptom relief with a first-line antidepressant treatment. Most likely, there are multiple causes of depression, yet it continues to be treated with a one-size-fits-all approach. Over time, when patients repeatedly receive the wrong treatment, they can begin to lose hope that there is anything they can do to combat their depression. That is why identifying who will respond to which treatment is critically important so that we can quickly intervene and effectively target symptoms of depression.
Perspectives
Does this mean that we are ready to start deploying anti-inflammatory treatments tomorrow? I personally don’t think so. Many of the more potent anti-inflammatory strategies analyzed in this study have side effects and long-term health risks. This concern is especially important given that depression often begins early in life, making these treatments particularly problematic for youth, especially at a time when chronic inflammation is on the rise and may affect as many as 40% of individuals aged 18–25. That said, I do think these findings support a causal role for immune dysfunction in depression for some individuals and underscore the urgency of identifying specific immune-based mechanisms that can be safely targeted with therapies, be they pharmacologic, behavioral, dietary, or nutritional supplements. Importantly, we need well-powered clinical trials to rigorously test this and identify the intervention, dose and duration that is needed.
Naoise Mac Giollabhui
Massachusetts General Hospital
Read the Original
This page is a summary of: 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, December 2025, American Psychiatric Association,
DOI: 10.1176/appi.ajp.20241115.
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