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

Abstract

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.

• Authors: Cristiano A Köhler, Thiago H Freitas, Brendon Stubbs, Michael Maes, Marco Solmi, Nicola Veronese, Nayanna Q de Andrade, Gerwyn Morris, Brisa S Fernandes, André R Brunoni, Nathan Herrmann, Charles L Raison, Brian J Miller, Krista L Lanctôt, André F Carvalho
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 55 Issue 5 Pg. 4195-4206 (May 2018) ISSN: 1559-1182 [Electronic] United States
• PMID: 28612257 (Publication Type: Journal Article, Meta-Analysis, Systematic Review)

Chemical References

• Antidepressive Agents
• Chemokines

Topics

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