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All Studies   Meta Analysis    Recent:   

Mortality Risk Among Patients With COVID-19 Prescribed Selective Serotonin Reuptake Inhibitor Antidepressants

Oskotsky et al., JAMA Network Open, doi:10.1001/jamanetworkopen.2021.33090
Nov 2021  
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Mortality -58% Improvement Relative Risk Mortality, fluoxetine 26% Fluvoxamine for COVID-19  Oskotsky et al.  Prophylaxis Is prophylaxis with fluvoxamine beneficial for COVID-19? PSM retrospective 7,696 patients in the USA Study underpowed for fluvoxamine, only 11 patients c19early.org Oskotsky et al., JAMA Network Open, Nov 2021 Favorsfluvoxamine Favorscontrol 0 0.5 1 1.5 2+
26th 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.
4,300+ studies for 75 treatments. c19early.org
Retrospective database analysis of 83,584 patients in the USA, showing lower mortality with existing fluoxetine use in PSM analysis. There were 11 fluvoxamine patients, showing non-statistically significant higher mortality.
risk of death, 57.9% higher, RR 1.58, p = 0.62, treatment 2 of 11 (18.2%), control 19 of 165 (11.5%), fluvoxamine.
risk of death, 26.0% lower, RR 0.74, p = 0.04, treatment 48 of 481 (10.0%), control 956 of 7,215 (13.3%), NNT 31, fluoxetine.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Oskotsky et al., 15 Nov 2021, retrospective, propensity score matching, USA, peer-reviewed, 8 authors.
This PaperFluvoxamineAll
Mortality Risk Among Patients With COVID-19 Prescribed Selective Serotonin Reuptake Inhibitor Antidepressants
Marić, Wong, Sirota, Stevenson. Tomiko Oskotsky, PhD Ivana Marić, BS Alice Tang, PhD; Boris Oskotsky, PhD Ronald J Wong, PhD Nima Aghaeepour, PhD Marina Sirota, MD David K Stevenson
JAMA Network Open, doi:10.1001/jamanetworkopen.2021.33090
IMPORTANCE Antidepressant use may be associated with reduced levels of several proinflammatory cytokines suggested to be involved with the development of severe COVID-19. An association between the use of selective serotonin reuptake inhibitors (SSRIs)-specifically fluoxetine hydrochloride and fluvoxamine maleate-with decreased mortality among patients with COVID-19 has been reported in recent studies; however, these studies had limited power due to their small size. OBJECTIVE To investigate the association of SSRIs with outcomes in patients with COVID-19 by analyzing electronic health records (EHRs). DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study used propensity score matching by demographic characteristics, comorbidities, and medication indication to compare SSRItreated patients with matched control patients not treated with SSRIs within a large EHR database representing a diverse population of 83 584 patients diagnosed with COVID-19 from January to September 2020 and with a duration of follow-up of as long as 8 months in 87 health care centers across the US. EXPOSURES Selective serotonin reuptake inhibitors and specifically (1) fluoxetine, (2) fluoxetine or fluvoxamine, and (3) other SSRIs (ie, not fluoxetine or fluvoxamine). MAIN OUTCOMES AND MEASURES Death. RESULTS A total of 3401 adult patients with COVID-19 prescribed SSRIs (2033 women [59.8%]; mean [SD] age, 63.8 [18.1] years) were identified, with 470 receiving fluoxetine only (280 women [59.6%]; mean [SD] age, 58.5 [18.1] years), 481 receiving fluoxetine or fluvoxamine (285 women [59.3%]; mean [SD] age, 58.7 [18.0] years), and 2898 receiving other SSRIs (1733 women [59.8%]; mean [SD] age, 64.7 [18.0] years) within a defined time frame. When compared with matched untreated control patients, relative risk (RR) of mortality was reduced among patients prescribed any SSRI (497 of 3401 [14.6%] vs 1130 of 6802 [16.6%]; RR, 0.92 [95% CI, 0.85-0.99]; adjusted P = .03); fluoxetine (46 of 470 [9.8%] vs 937 of 7050 [13.3%]; RR, 0.72 [95% CI, 0.54-0.97]; adjusted P = .03); and fluoxetine or fluvoxamine (48 of 481 [10.0%] vs 956 of 7215 [13.3%]; RR, 0.74 [95% CI, 0.55-0.99]; adjusted P = .04). The association between receiving any SSRI that is not fluoxetine or fluvoxamine and risk of death was not statistically significant (447 of 2898 [15.4%] vs 1474 of 8694 [17.0%]; RR, 0.92 [95% CI, 0.84-1.00]; adjusted P = .06). CONCLUSIONS AND RELEVANCE These results support evidence that SSRIs may be associated with reduced severity of COVID-19 reflected in the reduced RR of mortality. Further research and randomized clinical trials are needed to elucidate the effect of SSRIs generally, or more specifically of fluoxetine and fluvoxamine, on the severity of COVID-19 outcomes.
ARTICLE INFORMATION Accepted for Publication
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inhibitors, venlafaxine, ' 'and mirtazapine in major depression: a systematic review and ' 'dose-response meta-analysis.', 'volume': '6', 'author': 'Furukawa', 'year': '2019', 'journal-title': 'Lancet Psychiatry'}, { 'key': 'zoi210938r28', 'doi-asserted-by': 'crossref', 'DOI': '10.1016/j.mehy.2020.110140', 'article-title': 'The possible immunoregulatory and anti-inflammatory effects of ' 'selective serotonin reuptake inhibitors in coronavirus disease ' 'patients.', 'volume': '144', 'author': 'Hamed', 'year': '2020', 'journal-title': 'Med Hypotheses'}, { 'issue': '0', 'key': 'zoi210938r29', 'doi-asserted-by': 'crossref', 'first-page': '163', 'DOI': '10.1016/j.jocn.2021.03.010', 'article-title': 'Drug repurposing of selective serotonin reuptake inhibitors: could ' 'these drugs help fight COVID-19 and save lives?', 'volume': '88', 'author': 'Pashaei', 'year': '2021', 'journal-title': 'J Clin Neurosci'}, { 'issue': '1', 'key': 'zoi210938r30', 'doi-asserted-by': 'publisher', 'first-page': '29', 'DOI': '10.1016/j.coph.2011.02.004', 'article-title': '5-HT and the immune system.', 'volume': '11', 'author': 'Ahern', 'year': '2011', 'journal-title': 'Curr Opin Pharmacol'}, { 'issue': '5', 'key': 'zoi210938r31', 'first-page': '4195', 'article-title': 'Peripheral alterations in cytokine and chemokine levels after ' 'antidepressant drug treatment for major depressive disorder: systematic ' 'review and meta-analysis.', 'volume': '55', 'author': 'Köhler', 'year': '2018', 'journal-title': 'Mol Neurobiol'}, { 'issue': '1', 'key': 'zoi210938r32', 'doi-asserted-by': 'publisher', 'first-page': '474', 'DOI': '10.1111/j.1749-6632.1995.tb32372.x', 'article-title': 'Interleukin-6 serum levels in depressed patients before and after ' 'treatment with fluoxetine.', 'volume': '762', 'author': 'Sluzewska', 'year': '1995', 'journal-title': 'Ann N Y Acad Sci'}, { 'key': 'zoi210938r33', 'doi-asserted-by': 'publisher', 'first-page': '167', 'DOI': '10.1016/j.ejphar.2014.01.064', 'article-title': 'Interaction of new antidepressants with sigma-1 receptor chaperones and ' 'their potentiation of neurite outgrowth in PC12 cells.', 'volume': '727', 'author': 'Ishima', 'year': '2014', 'journal-title': 'Eur J Pharmacol'}, { 'issue': '3', 'key': 'zoi210938r34', 'doi-asserted-by': 'publisher', 'first-page': '209', 'DOI': '10.1016/S0924-8579(99)00157-0', 'article-title': 'Inhibition of HIV replication by neuroleptic agents and their potential ' 'use in HIV infected patients with AIDS related dementia.', 'volume': '14', 'author': 'Kristiansen', 'year': '2000', 'journal-title': 'Int J Antimicrob Agents'}, { 'issue': '9', 'key': 'zoi210938r35', 'doi-asserted-by': 'publisher', 'first-page': '4838', 'DOI': '10.1128/AAC.00983-12', 'article-title': 'Fluoxetine is a potent inhibitor of coxsackievirus replication.', 'volume': '56', 'author': 'Zuo', 'year': '2012', 'journal-title': 'Antimicrob Agents Chemother'}, { 'key': 'zoi210938r1', 'doi-asserted-by': 'crossref', 'article-title': 'Association 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M, . 6-Month follow up of 8679 ' 'hospitalized COVID-19 patients in Germany: a nationwide cohort study.? ' 'medRxiv. Preprint posted online April 24, 2012. ' 'doi:10.1101/2021.04.24.21256029', 'DOI': '10.1101/2021.04.24.21256029'}, { 'key': 'zoi210938r23', 'unstructured': 'ICD-10 Version:2019. Updated April 16, 2020. Accessed August 9, 2021. ' 'https://icd.who.int/browse10/2019/en#/U07.1'}, { 'key': 'zoi210938r27', 'unstructured': 'CDC/National Center for Health Statistics. Antidepressant use among ' 'adults: United States, 2015-2018. September 8, 2020. Accessed September ' '3, 2021. https://www.cdc.gov/nchs/products/databriefs/db377.htm'}], 'container-title': ['JAMA Network Open'], 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://jamanetwork.com/journals/jamanetworkopen/articlepdf/2786136/oskotsky_2021_oi_210938_1636051230.14579.pdf', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2021, 11, 15]], 'date-time': '2021-11-15T16:35:57Z', 'timestamp': 1636994157000}, 'score': 1, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2021, 11, 15]]}, 'references-count': 35, 'journal-issue': {'issue': '11', 'published-print': {'date-parts': [[2021, 11, 1]]}}, 'URL': 'http://dx.doi.org/10.1001/jamanetworkopen.2021.33090', 'relation': {}, 'ISSN': ['2574-3805'], 'issn-type': [{'value': '2574-3805', 'type': 'electronic'}], 'subject': ['General Medicine'], 'published': {'date-parts': [[2021, 11, 15]]}}
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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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