Sertraline as an Antidepressant and Inflammatory Cytokines in Depressive Disorders: A Systematic Review and Meta-Analysis of Randomized Double-Blind Placebo-Controlled Trials

Background: Sertraline, a selective serotonin reuptake inhibitor widely prescribed for depressive disorders, has been proposed to exert immunomodulatory effects through modulation of inflammatory pathways; however, clinical evidence regarding its effects on circulating cytokines remains inconsistent. This systematic review and meta-analysis evaluated the effects of sertraline on inflammatory cytokines in adults. Methods: Searches were conducted in LILACS, CINAHL, MEDLINE/PubMed, Cochrane Library, Scopus, and Web of Science to identify randomized single- or double-blind placebo-controlled trials assessing sertraline and inflammatory biomarkers. Ten studies met the eligibility criteria. Random-effects meta-analyses were performed for interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α). Results: Sertraline did not significantly reduce circulating IL-6 (MD −1.06, 95% CI −2.32 to 0.19; I2 = 86%; p = 0.10), IL-10 (MD < 0.01, 95% CI −0.23 to 0.23; I2 = 72%; p = 0.98), or TNF-α levels (MD −0.84, 95% CI −4.04 to 2.37; I2 = 72%; p = 0.61). Heterogeneity was substantial, all studies showed high overall risk of bias, and the certainty of evidence was very low for all outcomes. Conclusions: Current evidence does not support a significant or reliable anti-inflammatory effect of sertraline on circulating cytokines, and further well-designed trials using standardized inflammatory assessments are warranted.