Peripheral Alterations in Cytokine and Chemokine Levels After Antidepressant Drug Treatment for Major Depressive Disorder: Systematic Review and Meta-Analysis

Mol Neurobiol. 2018 May;55(5):4195-4206. doi: 10.1007/s12035-017-0632-1. Epub 2017 Jun 13.


Mounting evidence suggests that aberrations in immune-inflammatory pathways contribute to the pathophysiology of major depressive disorder (MDD), and individuals with MDD may have elevated levels of predominantly pro-inflammatory cytokines and C-reactive protein. In addition, previous meta-analyses suggest that antidepressant drug treatment may decrease peripheral levels of interleukin-1 beta (IL-1β) and IL-6. Recently, several new studies examining the effect of antidepressants on these cytokines have been published, and so we performed an updated meta-analysis of studies that measured peripheral levels of cytokines and chemokines during antidepressant treatment in patients with MDD. The PubMed/MEDLINE, EMBASE, and PsycInfo databases were searched from inception through March 9, 2017. Forty-five studies met inclusion criteria (N = 1517). Peripheral levels of IL-6, tumor necrosis factor-alpha (TNF-α), IL-1β, IL-10, IL-2, IL-4, interferon-γ, IL-8, the C-C motif ligand 2 chemokine (CCL-2), CCL-3, IL-1 receptor antagonist, IL-13, IL-17, IL-5, IL-7, and the soluble IL-2 receptor were measured in at least three datasets and thus were meta-analyzed. Antidepressant treatment significantly decreased peripheral levels of IL-6 (Hedges g = -0.454, P <0.001), TNF-α (g = -0.202, P = 0.015), IL-10 (g = -0.566, P = 0.012), and CCL-2 (g = -1.502, P = 0.006). These findings indicate that antidepressants decrease several markers of peripheral inflammation. However, this meta-analysis did not provide evidence that reductions in peripheral inflammation are associated with antidepressant treatment response although few studies provided separate data for treatment responders and non-responders.

Keywords: Antidepressant; Chemokines; Cytokines; Depression; Inflammation; Meta-analysis.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Antidepressive Agents / pharmacology
  • Antidepressive Agents / therapeutic use*
  • Chemokines / metabolism*
  • Depressive Disorder, Major / drug therapy*
  • Humans
  • Treatment Outcome


  • Antidepressive Agents
  • Chemokines