Inflammatory modulation of fluoxetine use in patients with depression: A systematic review and meta-analysis

There is growing evidence that there is a relationship between major depressive disorder (MDD), also simply known as "depression", and inflammatory processes. Selective serotonin inhibitors, such as fluoxetine, are used as a first-line treatment for depression, and it is hypothesized that its use can reduce levels of proinflammatory cytokines. The aim of this systematic review and meta-analysis is to enable a better understanding of how treatment with the antidepressant fluoxetine modulates inflammation, and the roles of the main cytokines in this process. Risk of bias (RoB) in the included studies was assessed using the Cochrane Risk of Bias Assessment tool for Non-randomized studies (RoBANS). In the meta-analysis, standardized mean difference (SMD) was used as a summary statistic and grouped statistics using the generic inverse variation method in RevMan 5 with random effects model. Heterogeneous changes in cytokine levels were also evaluated from the SMD forest plot of individual studies. After analysis, we observed that fluoxetine was able to decrease TNF-α levels (SMD ± 0.90, 95% CI = 0.16, 1.165, Z ± 2.40, p = 0.02), but not change IL-6 levels (SMD ± 0.37, 95% CI = 0.21, 0.95, Z ± 1.25, p = 0.21).Fluoxetine acts by modulating neuroimmunology, and not only by acting only on the independent restoration of neurotransmission and neuroinflammation pathways.