Abstract
BACKGROUND: Anti-inflammatory agents have emerged as a potential new therapy for major depressive disorder (MDD). In this meta-analysis, our aim was to evaluate the antidepressant effect of anti-inflammatory agents and compare their efficacy. METHODS: We conducted a comprehensive search across multiple databases, including PubMed, Embase, Web of Science, Cochrane Review, Cochrane Trial, and ClinicalTrials.gov, to identify eligible randomized clinical trials. The primary outcome measures of our meta-analysis were efficacy and acceptability, while the secondary outcome measures focused on remission rate and dropout rate due to adverse events. We used odds ratio (OR) and 95% confidence interval (95% CI) to present our results. RESULTS: A total of 48 studies were included in our analysis. In terms of efficacy, anti-inflammatory agents demonstrated a significant antidepressant effect compared to placebo (OR = 2.04, 95% CI: 1.41-2.97, p = 0.0002). Subgroup analyses revealed that anti-inflammatory agents also exhibited significant antidepressant effects in the adjunctive therapy subgroup (OR = 2.17, 95% CI: 1.39-3.37, p = 0.0006) and in MDD patients without treatment-resistant depression subgroup (OR = 2.33, 95% CI: 1.53-3.54, p < 0.0001). Based on the surface under the cumulative ranking curve (SUCRA) value of network meta-analysis, nonsteroidal anti-inflammatory drugs (NSAIDs) (SUCRA value = 81.6) demonstrated the highest acceptability among the included anti-inflammatory agents. CONCLUSION: In summary, our meta-analysis demonstrates that anti-inflammatory agents have significant antidepressant effects and are well-accepted. Furthermore, adjunctive therapy with anti-inflammatory agents proved effective in treating MDD. Among the evaluated anti-inflammatory agents, NSAIDs exhibited the highest acceptability, although its efficacy is comparable to placebo. SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=422004), identifier CRD42023422004.