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The effect of antidepressants on the severity of COVID-19 in hospitalized patients: A systematic review and meta-analysis

Nakhaee et al., PLOS ONE, doi:10.1371/journal.pone.0267423 (date from preprint)
Apr 2022  
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Meta analysis of 12 studies concluding that evidence supports the use of antidepressants, mainly fluvoxamine, for COVID-19. Fluvoxamine significantly reduced severity, RR 0.76 [0.60-0.97].
5 meta analyses show significant improvements with fluvoxamine for mortality Deng, hospitalization Deng, Lee, Lu, Marcec, and severity Nakhaee.
Nakhaee et al., 16 Apr 2022, peer-reviewed, 6 authors.
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The effect of antidepressants on the severity of COVID-19 in hospitalized patients: A systematic review and meta-analysis
Hosein Nakhaee, Moein Zangiabadian, Reza Bayati, Mohammad Rahmanian, Amir Ghaffari Jolfayi, Sakineh Rakhshanderou
PLOS ONE, doi:10.1371/journal.pone.0267423
Introduction Clinical Depression and the subsequent low immunity is a comorbidity that can act as a risk factor for the severity of COVID-19 cases. Antidepressants such as Selective serotonin reuptake inhibitor and Serotonin-norepinephrine reuptake inhibitors are associated with immune-modulatory effects, which dismiss inflammatory responses and reduce lung tissue damage. The current systematic review and meta-analysis aims to evaluate the effect of antidepressant drugs on the prognosis and severity of COVID-19 in hospitalized patients. Methods A systematic search was carried out in PubMed/Medline, EMBASE, and Scopus up to June 14, 2022. The following keywords were used: "COVID-19", "SARS-CoV-2", "2019-nCoV", "SSRI", "SNRI", "TCA", "MAOI", and "Antidepressant". A fixed or random-effect model assessed the pooled risk ratio (RR) with 95% CI. We considered P < 0.05 as statistically significant for publication bias. Data were analyzed by Comprehensive Meta-Analysis software, Version 2.0 (Biostat, Englewood, NJ). Results Fourteen studies were included in our systematic review. Five of them were experimental with 2350, and nine of them were observational with 290,950 participants. Eight out of fourteen articles revealed the effect of antidepressants on reducing the severity of COVID-19. Selective serotonin reuptake inhibitors drugs, including Fluvoxamine, Escitalopram, Fluoxetine, and Paroxetine, and among the Serotonin-norepinephrine inhibitors medications Venlafaxine, are reasonably associated with reduced risk of intubation or death. Five studies showed no significant effect, and only one high risk of bias article showed the negative effect of antidepressants on the prognosis of Covid-19. The meta-analysis of clinical trials showed
Author Contributions Data curation: Reza Bayati, Mohammad Rahmanian. Formal analysis: Moein Zangiabadian. Investigation: Reza Bayati, Mohammad Rahmanian, Amir Ghaffari Jolfayi. Methodology: Moein Zangiabadian. Supervision: Sakineh Rakhshanderou. Writing -original draft: Hosein Nakhaee, Moein Zangiabadian.
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Late treatment
is less effective
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