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The anti-inflammatory role of SSRI and SNRI in the treatment of depression: a review of human and rodent research studies

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Abstract

Rationale

Depression has the topmost prevalence of all psychiatric diseases. It is characterized by a high recurrence rate, disability, and numerous and mostly unclear pathogenic mechanisms. Besides the monoamine or the neurotrophic hypothesis of depression, the inflammatory mechanism has begun to be supported by more and more evidence. At the same time, the current knowledge about the standard treatment of choice, the selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs), is expanding rapidly, adding more features to the initial ones.

Objectives

This review summarizes the in vivo anti-inflammatory effects of SSRIs and SNRIs in the treatment of depression and outlines the particular mechanisms of these effects for each drug separately. In addition, we provide an overview of the inflammation-related theory of depression and the underlying mechanisms.

Results

SSRIs and SNRIs decrease the neuroinflammation through multiple mechanisms including the reduction of blood or tissue cytokines or regulating complex inflammatory pathways: nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), inflammasomes, Toll-like receptor 4 (TLR4), peroxisome proliferator-activated receptor gamma (PPARγ). Also, SSRIs and SNRIs show these effects in association with an antidepressant action.

Conclusions

SSRIs and SNRIs have an anti-neuroinflammatory role which might contribute the antidepressant effect.

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Data availability

All data relevant to the study are included in the article.

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Acknowledgements

We thank Mrs. Ioana Robu for the professional English language assistance.

Funding

The authors received no financial support for the research, authorship and/or publication of this article.

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  1. Vlad Dionisie, Gabriela Adriana Filip and Mihnea Costin Manea contributed equally to this work.

Authors and Affiliations

  1. Department of Psychiatry and Psychology, Faculty of Dental Medicine, “Carol Davila” University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021, Bucharest, Romania

    Vlad Dionisie, Mihnea Costin Manea & Mirela Manea

  2. Department of Physiology, “Iuliu Hatieganu” University of Medicine and Pharmacy, 1 Clinicilor Street, 400006, Cluj-Napoca, Romania

    Gabriela Adriana Filip

  3. ”Prof. Dr. Alexandru Obregia” Clinical Hospital of Psychiatry, 10 Berceni Road, 041914, Bucharest, Romania

    Vlad Dionisie, Mihnea Costin Manea, Mirela Manea & Sorin Riga

  4. Romanian Academy of Medical Sciences, 1 IC Bratianu Boulevard, 927180, Bucharest, Romania

    Sorin Riga

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  1. Vlad Dionisie
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VD had the idea for the article. VD and MM performed the literature search and data analysis. VD and MCM drafted the manuscript. GAF and SR critically revised the work.

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Dionisie, V., Filip, G.A., Manea, M.C. et al. The anti-inflammatory role of SSRI and SNRI in the treatment of depression: a review of human and rodent research studies. Inflammopharmacol 29, 75–90 (2021). https://doi.org/10.1007/s10787-020-00777-5

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