The Place of Fluvoxamine in the Treatment of Non-critically ill Patients with COVID-19: A Living Systematic Review and Meta-analysis

Abstract

Background: Fluvoxamine is a selective serotonin reuptake inhibitor that is known to be used as antidepressant. Repurposing of Fluvoxamine for the treatment of COVID-19 is theorized to help in the prevention of the clinical deterioration of SARS CoV-2 patients. In our systematic review and meta-analysis, we aim to assess the safety and efficacy of the drug under study in terms of its effect on the mortality and the risk of hospitalization and mechanical ventilation in non-critically ill COVID-19 patients. Methods: We performed a systematic search of seven electronic databases. The search results were screened based on the previously determined inclusion and exclusion criteria. We determined the data related to our objectives. The mortality rates, rates of hospitalization, risk of mechanical ventilation and serious side effects were extracted from the studies that successfully met our inclusion and exclusion criteria. Then, the extracted data from the included studies was included in the meta-analysis. Results: Three studies, two randomized clinical trials and one observational cohort study, with 1762 patients, were the final outcome of our search and screening processes. Among all participants, 886 patients received Fluvoxamine while 876 were controls. Follow up periods ranged from 7 days to 28 days. There was no significant difference in the intention-to-treat mortality rates between the two groups (RR = 0.66; 95% CI: 0.36 - 1.21, p-value = 0.18; I2 = 0%). However, Fluvoxamine decreased the per-protocol mortality compared to both placebo alone or placebo/standard care (RR = 0.09; 95% CI: 0.01 - 0.64, p-value = 0.02; I2 = 0% and RR = 0.09; 95% CI: 0.01 - 0.72, respectively). As compared to placebo or standard care, the all-cause hospitalization was significantly reduced in the fluvoxamine group (RR = 0.71; 95% CI: 0.54 - 0.93, p-value = 0.01; I2 = 61%). This risk reduction was not significant when compared to placebo alone (RR = 0.76; 95% CI: 0.57 - 1.00; p-value = 0.051; I2 = 48%). Furthermore, the risk of mechanical ventilation was not improved in the fluvoxamine group as compared to placebo (RR = 0.71; 95% CI: 0.43 - 1.16, p-value = 0.17; I2 = 0%). The serious adverse effects were almost the same in the treatment group and the control (13% and 12% respectively). Conclusion: Fluvoxamine does not significantly reduce the mortality rates or the risk of mechanical ventilation in SARS CoV-2 patients. Nonetheless, it was found to have a good impact on reducing all cause hospitalization among patients with COVID-19 disease. Therefore, further clinical studies are needed to determine the effectiveness of the drug and its mechanisms of action.

Selective serotonin reuptake inhibitors: New hope in the fight against COVID-19

“…It suggests that Sig-1R as functional host-dependency factors for SARS-CoV-2, thus a key target for COVID-19 agent replication (Hashimoto and neuroscience, 2021). With this in hand, fluvoxamine, an effective Sig-1R agonist with immunomodulatory functions in animal studies, has been employed in the trials further to inspect the potential anti-viral properties ( Oussama Kacimi et al, 2021 ). Many theories investigate that inhibition of platelet aggregation, mast cell degranulation, and lysosomotropic associate the mechanisms that fluvoxamine might take to intervene in COVID-19 affliction efficiently ( Navin et al, 2020 ).…”

“…Sertraline and paroxetine attenuate mitogen-stimulated increases of STAT3 and Cyclooxygenases-2, which are also involved in COVID-19 immunopathology. This function is more prominent than dexamethasone, another keystone in COVID-19 therapy ( Oussama Kacimi et al, 2021 ).…”