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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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27th treatment shown to reduce risk in November 2021
 
*, now with p = 0.00014 from 21 studies, recognized in 3 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 79 treatments. c19early.org
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].
8 meta analyses show significant improvements with fluvoxamine for mortality1,2, hospitalization1,3-7, progression2,7, and severity8.
Nakhaee et al., 16 Apr 2022, peer-reviewed, 6 authors. Contact: zangiabadian1998@gmail.com, s_rakhshanderou@sbmu.ac.ir.
This PaperFluvoxamineAll
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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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.</jats:p>\n' '</jats:sec>\n' '<jats:sec id="sec002">\n' '<jats:title>Methods</jats:title>\n' '<jats:p>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 &lt; 0.05 as statistically significant ' 'for publication bias. Data were analyzed by Comprehensive Meta-Analysis software, Version 2.0 ' '(Biostat, Englewood, NJ).</jats:p>\n' '</jats:sec>\n' '<jats:sec id="sec003">\n' '<jats:title>Results</jats:title>\n' '<jats:p>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 that fluvoxamine could significantly decrease the severity outcomes of COVID-19 (RR: ' '0.763; 95% CI: 0.602–0.966, I2: 0.0)</jats:p>\n' '</jats:sec>\n' '<jats:sec id="sec004">\n' '<jats:title>Findings</jats:title>\n' '<jats:p>Most evidence supports that the use of antidepressant medications, mainly ' 'Fluvoxamine, may decrease the severity and improve the outcome in hospitalized patients with ' 'SARS-CoV-2. Some studies showed contradictory findings regarding the effects of ' 'antidepressants on the severity of COVID-19. 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Higgins', 'year': '2002', 'journal-title': 'Statistics in medicine'}, { 'key': 'pone.0267423.ref016', 'doi-asserted-by': 'crossref', 'first-page': '1088', 'DOI': '10.2307/2533446', 'article-title': 'Operating characteristics of a rank correlation test for publication ' 'bias', 'author': 'C.B. Begg', 'year': '1994', 'journal-title': 'Biometrics'}, { 'key': 'pone.0267423.ref017', 'first-page': '991', 'article-title': 'Is it possible that antidepressants protect against COVID-19?', 'author': 'E.S. Bora', 'year': '2021', 'journal-title': 'Annals of Clinical and Analytical Medicine'}, { 'key': 'pone.0267423.ref018', 'article-title': 'Can SSRI/SNRI antidepressants decrease the’cytokine storm’in the course ' 'of COVID-19 pneumonia?', 'author': 'L. 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Late treatment
is less effective
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
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