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

Cytokine. 2020 Jul:131:155100. doi: 10.1016/j.cyto.2020.155100. Epub 2020 Apr 18.

Abstract

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.

Keywords: Cytokine; Fluoxetine; Inflammatory; Interleukin.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antidepressive Agents, Second-Generation / therapeutic use*
  • Child
  • Depressive Disorder, Major / blood
  • Depressive Disorder, Major / drug therapy*
  • Fluoxetine / therapeutic use*
  • Humans
  • Inflammation Mediators / blood
  • Interleukin-6 / blood*
  • Middle Aged
  • Selective Serotonin Reuptake Inhibitors / therapeutic use*
  • Tumor Necrosis Factor-alpha / blood*
  • Young Adult

Substances

  • Antidepressive Agents, Second-Generation
  • IL6 protein, human
  • Inflammation Mediators
  • Interleukin-6
  • Serotonin Uptake Inhibitors
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • Fluoxetine