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Effects of SSRIs on peripheral inflammatory markers in patients with major depressive disorder: a systematic review and meta-analysis

Effects of SSRIs on peripheral inflammatory markers in patients with major depressive disorder: a systematic review and meta-analysis
Effects of SSRIs on peripheral inflammatory markers in patients with major depressive disorder: a systematic review and meta-analysis
Introduction: Peripheral levels of inflammatory markers are elevated in major depressive disorder (MDD). Selective serotonin reuptake inhibitors (SSRIs) affect levels of inflammatory markers in patients with MDD, but studies have reported inconsistent findings. This systematic review and meta-analysis aims to investigate the effects of SSRI treatment on peripheral levels of a range of inflammatory markers in MDD patients. Methods: Systematic literature search (Pubmed, Web of Science, Embase, Cochrane) for studies published before
November 2018. Studies were included if they used SSRI monotherapy and peripheral levels of interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were measured before and after treatment in patients with MDD. Meta-analysis was conducted using Comprehensive Meta-analysis (version 2). Effect sizes were calculated using bias-corrected standardized mean difference (Hedges’ g) between pre- and post-treatment. Sub-group analyses, meta-regression and publication bias estimates were undertaken; sensitivity analyses were performed using different estimated pre- and post-treatment correlations and after removing poor quality studies.
Results: Twenty two eligible studies including 827 MDD patients were included in the meta-analysis: fifteen studies for IL-6; eleven for TNF-α; eight for IL-10; seven for IL-1β; six for IL-4; five for IL-2; and four for IFN-γ. The pooled effect estimate indicates SSRI treatment decreased levels of pro-inflammatory markers IL-6 (Hedges’ g, -0.418; 95%CI, −0.663 to −0.174; I⁠2=89.412), TNF-α (Hedges’ g, −0.554; 95%CI, −0.990 to −0.118; I⁠2=95.438) and IL-1β (Hedges’ g=−0.574; 95%CI, −1.014 to −0.135; I⁠2=91.622), and anti-inflammatory marker IL-10 (Hedges’ g=−0.615; 95%CI, −0.989 to −0.242; I⁠2=90.406). There were no significant treatment effects on levels of IL-2, IL-4, or IFN-γ. There was a high level of heterogeneity between studies. Sensitivity analyses indicated the robustness of the primary analyses. Conclusions: The current review and meta-analysis indicates moderate immunomodulating effects of SSRI treatment
for MDD, which suggests SSRIs may owe some of their therapeutic effect to their anti-inflammatory properties. High heterogeneity across studies may limit interpretation of the findings and larger randomized clinical trials are warranted.
0889-1591
24-38
Wang, Lina
2693c9b9-ae7d-4c2b-8867-adc2c53bf4df
Wang, Ruzhan
8fc87376-e3f9-47af-9957-df30348a7d3a
Liu, Lanfen
8925ae63-9bad-4d39-b5d9-bab4f3cef606
Qiao, Dongdong
a11b05f7-feb7-46f0-bdd4-3eafcaf18789
Baldwin, David
1beaa192-0ef1-4914-897a-3a49fc2ed15e
Hou, Ruihua
470bdcbc-93a9-4dad-aac5-26d455c34376
Wang, Lina
2693c9b9-ae7d-4c2b-8867-adc2c53bf4df
Wang, Ruzhan
8fc87376-e3f9-47af-9957-df30348a7d3a
Liu, Lanfen
8925ae63-9bad-4d39-b5d9-bab4f3cef606
Qiao, Dongdong
a11b05f7-feb7-46f0-bdd4-3eafcaf18789
Baldwin, David
1beaa192-0ef1-4914-897a-3a49fc2ed15e
Hou, Ruihua
470bdcbc-93a9-4dad-aac5-26d455c34376

Wang, Lina, Wang, Ruzhan, Liu, Lanfen, Qiao, Dongdong, Baldwin, David and Hou, Ruihua (2019) Effects of SSRIs on peripheral inflammatory markers in patients with major depressive disorder: a systematic review and meta-analysis. Brain, Behavior and Immunity, 79, 24-38. (doi:10.1016/j.bbi.2019.02.021).

Record type: Article

Abstract

Introduction: Peripheral levels of inflammatory markers are elevated in major depressive disorder (MDD). Selective serotonin reuptake inhibitors (SSRIs) affect levels of inflammatory markers in patients with MDD, but studies have reported inconsistent findings. This systematic review and meta-analysis aims to investigate the effects of SSRI treatment on peripheral levels of a range of inflammatory markers in MDD patients. Methods: Systematic literature search (Pubmed, Web of Science, Embase, Cochrane) for studies published before
November 2018. Studies were included if they used SSRI monotherapy and peripheral levels of interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ were measured before and after treatment in patients with MDD. Meta-analysis was conducted using Comprehensive Meta-analysis (version 2). Effect sizes were calculated using bias-corrected standardized mean difference (Hedges’ g) between pre- and post-treatment. Sub-group analyses, meta-regression and publication bias estimates were undertaken; sensitivity analyses were performed using different estimated pre- and post-treatment correlations and after removing poor quality studies.
Results: Twenty two eligible studies including 827 MDD patients were included in the meta-analysis: fifteen studies for IL-6; eleven for TNF-α; eight for IL-10; seven for IL-1β; six for IL-4; five for IL-2; and four for IFN-γ. The pooled effect estimate indicates SSRI treatment decreased levels of pro-inflammatory markers IL-6 (Hedges’ g, -0.418; 95%CI, −0.663 to −0.174; I⁠2=89.412), TNF-α (Hedges’ g, −0.554; 95%CI, −0.990 to −0.118; I⁠2=95.438) and IL-1β (Hedges’ g=−0.574; 95%CI, −1.014 to −0.135; I⁠2=91.622), and anti-inflammatory marker IL-10 (Hedges’ g=−0.615; 95%CI, −0.989 to −0.242; I⁠2=90.406). There were no significant treatment effects on levels of IL-2, IL-4, or IFN-γ. There was a high level of heterogeneity between studies. Sensitivity analyses indicated the robustness of the primary analyses. Conclusions: The current review and meta-analysis indicates moderate immunomodulating effects of SSRI treatment
for MDD, which suggests SSRIs may owe some of their therapeutic effect to their anti-inflammatory properties. High heterogeneity across studies may limit interpretation of the findings and larger randomized clinical trials are warranted.

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Accepted/In Press date: 20 February 2019
e-pub ahead of print date: 21 February 2019
Published date: July 2019

Identifiers

Local EPrints ID: 428929
URI: http://eprints.soton.ac.uk/id/eprint/428929
ISSN: 0889-1591
PURE UUID: 1d57146e-b0b4-4911-9907-eaeb9be426d6
ORCID for David Baldwin: ORCID iD orcid.org/0000-0003-3343-0907
ORCID for Ruihua Hou: ORCID iD orcid.org/0000-0001-6127-1478

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Date deposited: 14 Mar 2019 17:30
Last modified: 09 Jan 2022 08:03

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Contributors

Author: Lina Wang
Author: Ruzhan Wang
Author: Lanfen Liu
Author: Dongdong Qiao
Author: David Baldwin ORCID iD
Author: Ruihua Hou ORCID iD

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