Vlad Dionisie1,2, Gabriela Adriana Filip3, Mihnea Costin Manea4,5, Mirela Manea4,5, Sorin Riga5,6. 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@gmail.com. 2. "Prof. Dr. Alexandru Obregia" Clinical Hospital of Psychiatry, 10 Berceni Road, 041914, Bucharest, Romania. vlad.dionisie@gmail.com. 3. Department of Physiology, "Iuliu Hatieganu" University of Medicine and Pharmacy, 1 Clinicilor Street, 400006, Cluj-Napoca, Romania. 4. Department of Psychiatry and Psychology, Faculty of Dental Medicine, "Carol Davila" University of Medicine and Pharmacy, 37 Dionisie Lupu Street, 020021, Bucharest, Romania. 5. "Prof. Dr. Alexandru Obregia" Clinical Hospital of Psychiatry, 10 Berceni Road, 041914, Bucharest, Romania. 6. Romanian Academy of Medical Sciences, 1 IC Bratianu Boulevard, 927180, Bucharest, Romania.
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.
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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