key: cord-0875249-0i5b29gl authors: Pashaei, Yaser title: Drug repurposing of selective serotonin reuptake inhibitors: could these drugs help fight COVID-19 and save lives? date: 2021-03-19 journal: J Clin Neurosci DOI: 10.1016/j.jocn.2021.03.010 sha: 7a52ed4cb52cfc38fe765e1db18a89e6423c3d47 doc_id: 875249 cord_uid: 0i5b29gl The current 2019 novel coronavirus disease (COVID-19), an emerging infectious disease, is undoubtedly the most challenging pandemic in the 21st century. A total of 92,977,768 confirmed cases of COVID-19 and 1,991,289 deaths were reported globally up to January 14, 2021. COVID-19 also affects people’s mental health and quality of life. At present, there is no effective therapeutic strategy for the management of this disease. Therefore, in the absence of a specific vaccine or curative treatment, it is an urgent need to identify safe, effective and globally available drugs for reducing COVID-19 morbidity and fatalities. In this review, we focus on selective serotonin reuptake inhibitors (SSRIs: a class of antidepressant drugs with widespread availability and an optimal tolerability profile) that can potentially be repurposed for COVID-19 and are currently being tested in clinical trials. We also summarize the existing literature on what is known about the link between serotonin (5-HT) and the immune system. From the evidence reviewed here, we propose fluoxetine as an adjuvant therapeutic agent for COVID-19 based on its known immunomodulatory, anti-inflammatory and antiviral properties. Fluoxetine may potentially reduce pro-inflammatory chemokine/cytokines levels (such as CCL-2, IL-6, and TNF-α) in COVID-19 patients. Furthermore, fluoxetine may help to attenuate neurological complications of COVID-19. isoenzymes, they and some of their metabolites can indeed inhibit the CYP isoenzymes (see Table 1 for 185 further details) [55] . Table 1 [57] demonstrated that in vitro exposure of mononuclear cells to fluoxetine and paroxetine directly 195 increase NK-cell activity. Several authors also found significant increases in NK cells counts or activity [69] found that sertraline and fluoxetine significantly reduced IFN-γ and increased IL-10 218 production. Hence, both SSRIs significantly decreased the IFN-γ/IL-10 production ratio. Tuglu et al. [70] 219 found a significant decrease of TNF-α plasma levels after 6 weeks of SSRI treatment. Sluzewska et al. [71] also found a decrease of elevated IL-6 levels in depressed patients after 8 weeks of fluoxetine. [92] found that an increase in IL-6 levels 259 during 8 weeks of fluoxetine treatment is a risk factor for the emergence of SSRI-associated suicidality. In general, despite some conflicting data, it appears that SSRI drugs are able to modulate the immune 261 response. 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These drugs should not be co-administered; Zone