Association of fluvoxamine with mortality and symptom resolution among inpatients with COVID-19 in Uganda: a prospective interventional open-label cohort study

{ 'indexed': {'date-parts': [[2023, 3, 4]], 'date-time': '2023-03-04T05:44:07Z', 'timestamp': 1677908647897}, 'reference-count': 66, 'publisher': 'Springer Science and Business Media LLC', 'license': [ { 'start': { 'date-parts': [[2023, 3, 3]], 'date-time': '2023-03-03T00:00:00Z', 'timestamp': 1677801600000}, 'content-version': 'tdm', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}, { 'start': { 'date-parts': [[2023, 3, 3]], 'date-time': '2023-03-03T00:00:00Z', 'timestamp': 1677801600000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0'}], 'funder': [{'name': 'Government of Uganda through Makerere University Research and Innovations Fund'}], 'content-domain': {'domain': ['link.springer.com'], 'crossmark-restriction': False}, 'abstract': '<jats:title>Abstract</jats:title><jats:p>Prior research suggests that fluvoxamine, a ' 'selective serotonin reuptake inhibitor (SSRI) used for the treatment of obsessive-compulsive ' 'disorder and major depressive disorder, could be repurposed against COVID-19. We undertook a ' 'prospective interventional open-label cohort study to evaluate the efficacy and tolerability ' 'of fluvoxamine among inpatients with laboratory-confirmed COVID-19 in Uganda. The main ' 'outcome was all-cause mortality. Secondary outcomes were hospital discharge and complete ' 'symptom resolution. We included 316 patients, of whom 94 received fluvoxamine in addition to ' 'standard care [median age, 60 years (IQR\u2009=\u200937.0); women, 52.2%]. Fluvoxamine use ' 'was significantly associated with reduced mortality [AHR\u2009=\u20090.32; 95% CI\u2009=\u2009' '0.19–0.53; <jats:italic>p</jats:italic>\u2009&lt;\u20090.001, NNT\u2009=\u20094.46] and with ' 'increased complete symptom resolution [AOR\u2009=\u20092.56; 95% CI\u2009=\u20091.53–5.51; ' '<jats:italic>p</jats:italic>\u2009&lt;\u20090.001, NNT\u2009=\u20094.44]. Sensitivity ' 'analyses yielded similar results. These effects did not significantly differ by clinical ' 'characteristic, including vaccination status. Among the 161 survivors, fluvoxamine was not ' 'significantly associated with time to hospital discharge [AHR 0.81, 95% CI (0.54–1.23), ' '<jats:italic>p</jats:italic>\u2009=\u20090.32]. There was a trend toward greater side effects ' 'with fluvoxamine (7.45% versus 3.15%; SMD\u2009=\u20090.21; ' '<jats:italic>χ</jats:italic><jats:sup>2</jats:sup>\u2009=\u20093.46, ' '<jats:italic>p</jats:italic>\u2009=\u20090.06), most of which were light or mild in severity ' 'and none of which were serious. One hundred mg of fluvoxamine prescribed twice daily for 10 ' 'days was well tolerated and significantly associated with reduced mortality and with ' 'increased complete symptom resolution, without a significant increase in time to hospital ' 'discharge, among inpatients with COVID-19. Large-scale randomized trials are urgently needed ' 'to confirm these findings, especially for low- and middle-income countries, where access to ' 'vaccines and approved treatments against COVID-19 is limited.</jats:p>', 'DOI': '10.1038/s41380-023-02004-3', 'type': 'journal-article', 'created': {'date-parts': [[2023, 3, 3]], 'date-time': '2023-03-03T09:02:28Z', 'timestamp': 1677834148000}, 'update-policy': 'http://dx.doi.org/10.1007/springer_crossmark_policy', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Association of fluvoxamine with mortality and symptom resolution among inpatients with COVID-19 ' 'in Uganda: a prospective interventional open-label cohort study', 'prefix': '10.1038', 'author': [ {'given': 'Bruce J.', 'family': 'Kirenga', 'sequence': 'first', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-9423-2472', 'authenticated-orcid': False, 'given': 'Levicatus', 'family': 'Mugenyi', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-1121-8641', 'authenticated-orcid': False, 'given': 'Marina', 'family': 'Sánchez-Rico', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0001-6593-8727', 'authenticated-orcid': False, 'given': 'Henry', 'family': 'Kyobe', 'sequence': 'additional', 'affiliation': []}, {'given': 'Winters', 'family': 'Muttamba', 'sequence': 'additional', 'affiliation': []}, {'given': 'Raymond', 'family': 'Mugume', 'sequence': 'additional', 'affiliation': []}, {'given': 'Eliya', 'family': 'Mwesigwa', 'sequence': 'additional', 'affiliation': []}, {'given': 'Ezra', 'family': 'Kalimo', 'sequence': 'additional', 'affiliation': []}, {'given': 'Vicky', 'family': 'Nyombi', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0002-4535-1694', 'authenticated-orcid': False, 'given': 'Ivan', 'family': 'Segawa', 'sequence': 'additional', 'affiliation': []}, {'given': 'Loryndah Olive', 'family': 'Namakula', 'sequence': 'additional', 'affiliation': []}, {'given': 'Rogers', 'family': 'Sekibira', 'sequence': 'additional', 'affiliation': []}, {'given': 'Wilberforce', 'family': 'Kabweru', 'sequence': 'additional', 'affiliation': []}, {'given': 'Rosemary', 'family': 'Byanyima', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0003-3159-4318', 'authenticated-orcid': False, 'given': 'Hellen', 'family': 'Aanyu', 'sequence': 'additional', 'affiliation': []}, { 'ORCID': 'http://orcid.org/0000-0003-0757-1968', 'authenticated-orcid': False, 'given': 'Pauline', 'family': 'Byakika-Kibwika', 'sequence': 'additional', 'affiliation': []}, {'given': 'Henry G.', 'family': 'Mwebesa', 'sequence': 'additional', 'affiliation': []}, {'given': 'Nicolas', 'family': 'Hoertel', 'sequence': 'additional', 'affiliation': []}, {'given': 'William', 'family': 'Bazeyo', 'sequence': 'additional', 'affiliation': []}], 'member': '297', 'published-online': {'date-parts': [[2023, 3, 3]]}, 'reference': [ { 'key': '2004_CR1', 'doi-asserted-by': 'publisher', 'first-page': '365', 'DOI': '10.1080/10408363.2020.1783198', 'volume': '57', 'author': 'M Ciotti', 'year': '2020', 'unstructured': 'Ciotti M, Ciccozzi M, Terrinoni A, Jiang WC, Wang CB, Bernardini S. The ' 'COVID-19 pandemic. Crit Rev Clin Lab Sci. 2020;57:365–88.', 'journal-title': 'Crit Rev Clin Lab Sci'}, { 'key': '2004_CR2', 'doi-asserted-by': 'publisher', 'first-page': '193', 'DOI': '10.1016/j.encep.2020.04.005', 'volume': '46', 'author': 'A Chevance', 'year': '2020', 'unstructured': 'Chevance A, Gourion D, Hoertel N, Llorca PM, Thomas P, Bocher P, et al. ' 'Ensuring mental health care during the SARS-CoV-2 epidemic in France: a ' 'narrative review. L’Encéphale. 2020;46:193–201.', 'journal-title': 'L’Encéphale'}, { 'key': '2004_CR3', 'doi-asserted-by': 'publisher', 'first-page': '1417', 'DOI': '10.1038/s41591-020-1001-6', 'volume': '26', 'author': 'N Hoertel', 'year': '2020', 'unstructured': 'Hoertel N, Blachier M, Blanco C, Olfson M, Masseti M, Sánchez-Rico M, et ' 'al. A stochastic agent-based model of the SARS-CoV-2 epidemic in France. ' 'Nat Med. 2020;26:1417–21.', 'journal-title': 'Nat Med'}, { 'key': '2004_CR4', 'doi-asserted-by': 'publisher', 'first-page': '1513', 'DOI': '10.1016/S0140-6736(21)02796-3', 'volume': '399', 'author': 'H Wang', 'year': '2022', 'unstructured': 'Wang H, Paulson KR, Pease SA, Watson S, Comfort H, Zheng P, et al. ' 'Estimating excess mortality due to the COVID-19 pandemic: a systematic ' 'analysis of COVID-19-related mortality, 2020–21. Lancet. ' '2022;399:1513–36.', 'journal-title': 'Lancet'}, { 'key': '2004_CR5', 'doi-asserted-by': 'publisher', 'first-page': '4609', 'DOI': '10.2147/RMHP.S339408', 'volume': '14', 'author': 'P Musoke', 'year': '2021', 'unstructured': 'Musoke P, Okot J, Nanfuka V, Rwamafa P, Masajjage J, Kisuule I, et al. A ' 'preliminary report on herbal medicine use among patients hospitalized at ' 'two-large COVID-19 treatment centers in Uganda. RMHP. 2021;14:4609–17.', 'journal-title': 'RMHP'}, { 'key': '2004_CR6', 'doi-asserted-by': 'publisher', 'first-page': '1774', 'DOI': '10.1056/NEJMc2101927', 'volume': '384', 'author': 'J Keehner', 'year': '2021', 'unstructured': 'Keehner J, Horton LE, Pfeffer MA, Longhurst CA, Schooley R, Currier JS, ' 'et al. SARS-CoV-2 infection after vaccination in health care workers in ' 'California. N Engl J Med. 2021;384:1774–5.', 'journal-title': 'N Engl J Med'}, { 'key': '2004_CR7', 'doi-asserted-by': 'publisher', 'first-page': 'ofac389', 'DOI': '10.1093/ofid/ofac389', 'volume': '9', 'author': 'S Lim', 'year': '2022', 'unstructured': 'Lim S, Tignanelli CJ, Hoertel N, Boulware DR, Usher MG. Prevalence of ' 'medical contraindications to nirmatrelvir/ritonavir in a cohort of ' 'hospitalized and nonhospitalized patients with COVID-19. Open Forum ' 'Infect Dis. 2022;9:ofac389.', 'journal-title': 'Open Forum Infect Dis'}, { 'key': '2004_CR8', 'doi-asserted-by': 'publisher', 'first-page': 'e2242140', 'DOI': '10.1001/jamanetworkopen.2022.42140', 'volume': '5', 'author': 'N Hoertel', 'year': '2022', 'unstructured': 'Hoertel N, Boulware DR, Sánchez-Rico M, Burgun A, Limosin F. Prevalence ' 'of contraindications to nirmatrelvir-ritonavir among hospitalized ' 'patients with COVID-19 at risk for progression to severe disease. JAMA ' 'Netw Open. 2022;5:e2242140.', 'journal-title': 'JAMA Netw Open'}, { 'key': '2004_CR9', 'doi-asserted-by': 'publisher', 'first-page': 'e2136510', 'DOI': '10.1001/jamanetworkopen.2021.36510', 'volume': '4', 'author': 'N Hoertel', 'year': '2021', 'unstructured': 'Hoertel N. Do the selective serotonin reuptake inhibitor antidepressants ' 'fluoxetine and fluvoxamine reduce mortality among patients with ' 'COVID-19. JAMA Netw Open. 2021;4:e2136510.', 'journal-title': 'JAMA Netw Open'}, { 'key': '2004_CR10', 'doi-asserted-by': 'publisher', 'first-page': '1278', 'DOI': '10.1038/s41380-021-01393-7', 'volume': '27', 'author': 'N Hoertel', 'year': '2022', 'unstructured': 'Hoertel N, Sánchez-Rico M, Herrera-Morueco JJ, de la Muela P, Gulbins E, ' 'Kornhuber J, et al. Comorbid medical conditions are a key factor to ' 'understand the relationship between psychiatric disorders and ' 'COVID-19-related mortality: results from 49,089 COVID-19 inpatients. Mol ' 'Psychiatry. 2022;27:1278–80.', 'journal-title': 'Mol Psychiatry'}, { 'key': '2004_CR11', 'doi-asserted-by': 'publisher', 'first-page': '7098', 'DOI': '10.1038/s41380-021-01254-3', 'volume': '26', 'author': 'N Hoertel', 'year': '2021', 'unstructured': 'Hoertel N, Sánchez-Rico M, Cougoule C, Gulbins E, Kornhuber J, ' 'Carpinteiro A, et al. Repurposing antidepressants inhibiting the ' 'sphingomyelinase acid/ceramide system against COVID-19: current evidence ' 'and potential mechanisms. Mol Psychiatry. 2021;26:7098–9.', 'journal-title': 'Mol Psychiatry'}, { 'key': '2004_CR12', 'doi-asserted-by': 'publisher', 'first-page': '57', 'DOI': '10.2165/00023210-199401010-00006', 'volume': '1', 'author': 'KJ Palmer', 'year': '1994', 'unstructured': 'Palmer KJ, Benfield P. Fluvoxamine: an overview of its pharmacological ' 'properties and review of its therapeutic potential in non-depressive ' 'disorders. CNS Drugs. 1994;1:57–87.', 'journal-title': 'CNS Drugs'}, { 'key': '2004_CR13', 'doi-asserted-by': 'publisher', 'first-page': 'e226269', 'DOI': '10.1001/jamanetworkopen.2022.6269', 'volume': '5', 'author': 'TC Lee', 'year': '2022', 'unstructured': 'Lee TC, Vigod S, Bortolussi-Courval É, Hanula R, Boulware DR, Lenze EJ, ' 'et al. Fluvoxamine for outpatient management of COVID-19 to prevent ' 'hospitalization: a systematic review and meta-analysis. JAMA Netw Open. ' '2022;5:e226269.', 'journal-title': 'JAMA Netw Open'}, { 'key': '2004_CR14', 'doi-asserted-by': 'publisher', 'first-page': '516', 'DOI': '10.1080/07853890.2022.2034936', 'volume': '54', 'author': 'W Wen', 'year': '2022', 'unstructured': 'Wen W, Chen C, Tang J, Wang C, Zhou M, Cheng Y, et al. Efficacy and ' 'safety of three new oral antiviral treatment (molnupiravir, fluvoxamine ' 'and Paxlovid) for COVID-19: a meta-analysis. Ann Med. 2022;54:516–23.', 'journal-title': 'Ann Med'}, { 'key': '2004_CR15', 'first-page': '00672', 'volume': 'S0163-4453', 'author': 'R Marcec', 'year': '2022', 'unstructured': 'Marcec R, Dodig VM, Likic R. A meta-analysis regarding fluvoxamine and ' 'hospitalization risk of COVID-19 patients: TOGETHER making a difference. ' 'J Infect. 2022;S0163-4453:00672–7.', 'journal-title': 'J Infect'}, { 'key': '2004_CR16', 'first-page': '00032', 'volume': 'S1198-743X', 'author': 'J Deng', 'year': '2023', 'unstructured': 'Deng J, Rayner D, Ramaraju HB, Abbas U, García C, Heybati K, et al. ' 'Efficacy and safety of selective serotonin reuptake inhibitors in ' 'COVID-19 management: a systematic review and meta-analysis. Clin ' 'Microbiol Infect. 2023;S1198-743X:00032–0.', 'journal-title': 'Clin Microbiol Infect'}, { 'key': '2004_CR17', 'doi-asserted-by': 'publisher', 'first-page': 'ofab050', 'DOI': '10.1093/ofid/ofab050', 'volume': '8', 'author': 'D Seftel', 'year': '2021', 'unstructured': 'Seftel D, Boulware DR. Prospective cohort of fluvoxamine for early ' 'treatment of Coronavirus Disease 19. Open Forum Infect Dis. ' '2021;8:ofab050.', 'journal-title': 'Open Forum Infect Dis'}, { 'key': '2004_CR18', 'doi-asserted-by': 'publisher', 'unstructured': 'Reis G, dos Santos Moreira-Silva EA, Silva DCM, Thabane L, Milagres AC, ' 'dos Santos CVQ, et al. Effect of early treatment with fluvoxamine on ' 'risk of emergency care and hospitalisation among patients with COVID-19: ' 'the TOGETHER randomised, platform clinical trial. Lancet Glob Health. ' '2021:S2214109X21004484. https://doi.org/10.1016/S2214-109X(21)00448-4.', 'DOI': '10.1016/S2214-109X(21)00448-4'}, { 'key': '2004_CR19', 'doi-asserted-by': 'publisher', 'first-page': '2292', 'DOI': '10.1001/jama.2020.22760', 'volume': '324', 'author': 'EJ Lenze', 'year': '2020', 'unstructured': 'Lenze EJ, Mattar C, Zorumski CF, Stevens A, Schweiger J, Nicol GE, et ' 'al. Fluvoxamine vs placebo and clinical deterioration in outpatients ' 'with symptomatic COVID-19: a randomized clinical trial. JAMA. ' '2020;324:2292–300.', 'journal-title': 'JAMA'}, { 'key': '2004_CR20', 'doi-asserted-by': 'publisher', 'unstructured': 'Calusic M, Marcec R, Luksa L, Jurkovic I, Novac N, Mihaljevic S, et al. ' 'Safety and efficacy of fluvoxamine in COVID-19 ICU patients: an open ' 'label, prospective cohort trial with matched controls. Br J Clin ' 'Pharmacol. 2021. https://doi.org/10.1111/bcp.15126.', 'DOI': '10.1111/bcp.15126'}, { 'key': '2004_CR21', 'doi-asserted-by': 'publisher', 'first-page': '599', 'DOI': '10.1056/NEJMoa2201662', 'volume': '387', 'author': 'CT Bramante', 'year': '2022', 'unstructured': 'Bramante CT, Huling JD, Tignanelli CJ, Buse JB, Liebovitz DM, Nicklas ' 'JM, et al. Randomized trial of metformin, ivermectin, and fluvoxamine ' 'for Covid-19. N Engl J Med. 2022;387:599–610.', 'journal-title': 'N Engl J Med'}, { 'key': '2004_CR22', 'doi-asserted-by': 'publisher', 'first-page': '2245', 'DOI': '10.1080/22221751.2020.1829082', 'volume': '9', 'author': 'S Schloer', 'year': '2020', 'unstructured': 'Schloer S, Brunotte L, Goretzko J, Mecate-Zambrano A, Korthals N, Gerke ' 'V, et al. Targeting the endolysosomal host-SARS-CoV-2 interface by ' 'clinically licensed functional inhibitors of acid sphingomyelinase ' '(FIASMA) including the antidepressant fluoxetine. Emerg Microbes Infect. ' '2020;9:2245–55.', 'journal-title': 'Emerg Microbes Infect'}, { 'key': '2004_CR23', 'doi-asserted-by': 'publisher', 'first-page': '100142', 'DOI': '10.1016/j.xcrm.2020.100142', 'volume': '1', 'author': 'A Carpinteiro', 'year': '2020', 'unstructured': 'Carpinteiro A, Edwards MJ, Hoffmann M, Kochs G, Gripp B, Weigang S, et ' 'al. Pharmacological inhibition of acid sphingomyelinase prevents uptake ' 'of SARS-CoV-2 by epithelial cells. Cell Rep Med. 2020;1:100142.', 'journal-title': 'Cell Rep Med'}, { 'key': '2004_CR24', 'doi-asserted-by': 'publisher', 'first-page': 'eaau5266', 'DOI': '10.1126/scitranslmed.aau5266', 'volume': '11', 'author': 'DA Rosen', 'year': '2019', 'unstructured': 'Rosen DA, Seki SM, Fernández-Castañeda A, Beiter R, Eccles J, Woodfolk ' 'JA, et al. Modulation of the sigma-1 receptor–IRE1 pathway is beneficial ' 'in preclinical models of inflammation and sepsis. Sci Transl Med. ' '2019;11:eaau5266.', 'journal-title': 'Sci Transl Med'}, { 'key': '2004_CR25', 'doi-asserted-by': 'publisher', 'first-page': '652688', 'DOI': '10.3389/fphar.2021.652688', 'volume': '12', 'author': 'VP Sukhatme', 'year': '2021', 'unstructured': 'Sukhatme VP, Reiersen AM, Vayttaden SJ, Sukhatme VV. Fluvoxamine: a ' 'review of its mechanism of action and its role in COVID-19. Front Pharm. ' '2021;12:652688.', 'journal-title': 'Front Pharm'}, { 'key': '2004_CR26', 'doi-asserted-by': 'publisher', 'first-page': '1898', 'DOI': '10.1038/s41380-021-01432-3', 'volume': '27', 'author': 'Y Hashimoto', 'year': '2022', 'unstructured': 'Hashimoto Y, Suzuki T, Hashimoto K. Mechanisms of action of fluvoxamine ' 'for COVID-19: a historical review. Mol Psychiatry. 2022;27:1898–907.', 'journal-title': 'Mol Psychiatry'}, { 'key': '2004_CR27', 'doi-asserted-by': 'publisher', 'first-page': '307', 'DOI': '10.1038/s41380-021-01309-5', 'volume': '27', 'author': 'J Kornhuber', 'year': '2022', 'unstructured': 'Kornhuber J, Hoertel N, Gulbins E. The acid sphingomyelinase/ceramide ' 'system in COVID-19. Mol Psychiatry. 2022;27:307–14.', 'journal-title': 'Mol Psychiatry'}, { 'key': '2004_CR28', 'doi-asserted-by': 'publisher', 'first-page': '771', 'DOI': '10.1136/pgmj.49.577.771', 'volume': '49', 'author': 'SDM Court', 'year': '1973', 'unstructured': 'Court SDM. The definition of acute respiratory illnesses in children. ' 'Postgrad Med J. 1973;49:771–6.', 'journal-title': 'Postgrad Med J'}, { 'key': '2004_CR29', 'doi-asserted-by': 'publisher', 'first-page': '636', 'DOI': '10.1016/j.tips.2019.07.006', 'volume': '40', 'author': 'HR Schmidt', 'year': '2019', 'unstructured': 'Schmidt HR, Kruse AC. The molecular function of σ receptors: past, ' 'present, and future. Trends Pharmacol Sci. 2019;40:636–54.', 'journal-title': 'Trends Pharmacol Sci'}, { 'key': '2004_CR30', 'doi-asserted-by': 'publisher', 'first-page': '167', 'DOI': '10.1016/j.ejphar.2014.01.064', 'volume': '727', 'author': 'T Ishima', 'year': '2014', 'unstructured': 'Ishima T, Fujita Y, Hashimoto K. Interaction of new antidepressants with ' 'sigma-1 receptor chaperones and their potentiation of neurite outgrowth ' 'in PC12 cells. Eur J Pharmacol. 2014;727:167–73.', 'journal-title': 'Eur J Pharmacol'}, { 'key': '2004_CR31', 'doi-asserted-by': 'publisher', 'first-page': '934', 'DOI': '10.1038/nm.3214', 'volume': '19', 'author': 'E Gulbins', 'year': '2013', 'unstructured': 'Gulbins E, Palmada M, Reichel M, Lüth A, Böhmer C, Amato D, et al. Acid ' 'sphingomyelinase–ceramide system mediates effects of antidepressant ' 'drugs. Nat Med. 2013;19:934–8.', 'journal-title': 'Nat Med'}, { 'key': '2004_CR32', 'doi-asserted-by': 'publisher', 'first-page': '100701', 'DOI': '10.1016/j.jbc.2021.100701', 'volume': '296', 'author': 'A Carpinteiro', 'year': '2021', 'unstructured': 'Carpinteiro A, Gripp B, Hoffmann M, Pöhlmann S, Hoertel N, Edwards MJ, ' 'et al. Inhibition of acid sphingomyelinase by ambroxol prevents ' 'SARS-CoV-2 entry into epithelial cells. J Biol Chem. 2021;296:100701.', 'journal-title': 'J Biol Chem'}, { 'key': '2004_CR33', 'doi-asserted-by': 'publisher', 'first-page': '1498', 'DOI': '10.1002/cpt.2317', 'volume': '110', 'author': 'N Hoertel', 'year': '2021', 'unstructured': 'Hoertel N, Sánchez-Rico M, Gulbins E, Kornhuber J, Carpinteiro A, Lenze ' 'EJ, et al. Association between FIASMAs and reduced risk of intubation or ' 'death in individuals hospitalized for severe COVID-19: an observational ' 'multicenter study. Clin Pharm Ther. 2021;110:1498–511.', 'journal-title': 'Clin Pharm Ther'}, { 'key': '2004_CR34', 'doi-asserted-by': 'publisher', 'first-page': '5199', 'DOI': '10.1038/s41380-021-01021-4', 'volume': '26', 'author': 'N Hoertel', 'year': '2021', 'unstructured': 'Hoertel N, Sánchez-Rico M, Vernet R, Beeker N, Jannot AS, Neuraz A, et ' 'al. Association between antidepressant use and reduced risk of ' 'intubation or death in hospitalized patients with COVID-19: results from ' 'an observational study. Mol Psychiatry. 2021;26:5199–212.', 'journal-title': 'Mol Psychiatry'}, { 'key': '2004_CR35', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/s41398-022-01804-5', 'volume': '12', 'author': 'N Hoertel', 'year': '2022', 'unstructured': 'Hoertel N, Sánchez-Rico M, Gulbins E, Kornhuber J, Carpinteiro A, ' 'Abellán M, et al. Association between FIASMA psychotropic medications ' 'and reduced risk of intubation or death in individuals with psychiatric ' 'disorders hospitalized for severe COVID-19: an observational multicenter ' 'study. Transl Psychiatry. 2022;12:90.', 'journal-title': 'Transl Psychiatry'}, { 'key': '2004_CR36', 'doi-asserted-by': 'publisher', 'first-page': '5882', 'DOI': '10.3390/jcm11195882', 'volume': '11', 'author': 'N Hoertel', 'year': '2022', 'unstructured': 'Hoertel N, Sánchez-Rico M, Kornhuber J, Gulbins E, Reiersen AM, Lenze E, ' 'et al. Antidepressant use and its association with 28-day mortality in ' 'inpatients with SARS-CoV-2: support for the FIASMA model against ' 'COVID-19. JCM. 2022;11:5882.', 'journal-title': 'JCM'}, { 'key': '2004_CR37', 'doi-asserted-by': 'publisher', 'first-page': 'e2133090', 'DOI': '10.1001/jamanetworkopen.2021.33090', 'volume': '4', 'author': 'T Oskotsky', 'year': '2021', 'unstructured': 'Oskotsky T, Maric I, Tang A, Oskotsky B, Wong RJ, Aghaeepour N, et al. ' 'Mortality risk among patients with COVID-19 prescribed selective ' 'serotonin reuptake inhibitor antidepressants. JAMA Netw Open. ' '2021;4:e2133090.', 'journal-title': 'JAMA Netw Open'}, { 'key': '2004_CR38', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/s41398-022-02109-3', 'volume': '12', 'author': 'BA Fritz', 'year': '2022', 'unstructured': 'Fritz BA, Hoertel N, Lenze EJ, Jalali F, Reiersen AM. Association ' 'between antidepressant use and ED or hospital visits in outpatients with ' 'SARS-CoV-2. Transl Psychiatry. 2022;12:341.', 'journal-title': 'Transl Psychiatry'}, { 'key': '2004_CR39', 'doi-asserted-by': 'publisher', 'first-page': '755600', 'DOI': '10.3389/fphar.2021.755600', 'volume': '12', 'author': 'SM Fred', 'year': '2022', 'unstructured': 'Fred SM, Kuivanen S, Ugurlu H, Casarotto PC, Levanov L, Saksela K, et ' 'al. Antidepressant and antipsychotic drugs reduce viral infection by ' 'SARS-CoV-2 and fluoxetine shows antiviral activity against the novel ' 'variants in vitro. Front Pharm. 2022;12:755600.', 'journal-title': 'Front Pharm'}, { 'key': '2004_CR40', 'doi-asserted-by': 'publisher', 'first-page': 'e0124522', 'DOI': '10.1128/jvi.01245-22', 'volume': '96', 'author': 'Y Chen', 'year': '2022', 'unstructured': 'Chen Y, Wu Y, Chen S, Zhan Q, Wu D, Yang C, et al. Sertraline is an ' 'effective SARS-CoV-2 entry inhibitor targeting the spike protein. J ' 'Virol. 2022;96:e0124522.', 'journal-title': 'J Virol'}, { 'key': '2004_CR41', 'doi-asserted-by': 'publisher', 'first-page': '121023', 'DOI': '10.1016/j.ijpharm.2021.121023', 'volume': '607', 'author': 'SE Khater', 'year': '2021', 'unstructured': 'Khater SE, El-khouly A, Abdel-Bar HM, Al-mahallawi AM, Ghorab DM. ' 'Fluoxetine hydrochloride loaded lipid polymer hybrid nanoparticles ' 'showed possible efficiency against SARS-CoV-2 infection. Int J Pharm. ' '2021;607:121023.', 'journal-title': 'Int J Pharm'}, { 'key': '2004_CR42', 'doi-asserted-by': 'publisher', 'first-page': '1400', 'DOI': '10.3390/pharmaceutics13091400', 'volume': '13', 'author': 'L Brunotte', 'year': '2021', 'unstructured': 'Brunotte L, Zheng S, Mecate-Zambrano A, Tang J, Ludwig S, Rescher U, et ' 'al. Combination therapy with fluoxetine and the nucleoside analog ' 'GS-441524 exerts synergistic antiviral effects against different ' 'SARS-CoV-2 variants in vitro. Pharmaceutics. 2021;13:1400.', 'journal-title': 'Pharmaceutics'}, { 'key': '2004_CR43', 'doi-asserted-by': 'publisher', 'first-page': '339', 'DOI': '10.3390/microorganisms9020339', 'volume': '9', 'author': 'A Dechaumes', 'year': '2021', 'unstructured': 'Dechaumes A, Nekoua MP, Belouzard S, Sane F, Engelmann I, Dubuisson J, ' 'et al. Fluoxetine can inhibit SARS-CoV-2 in vitro. Microorganisms. ' '2021;9:339.', 'journal-title': 'Microorganisms'}, { 'key': '2004_CR44', 'doi-asserted-by': 'publisher', 'first-page': '2339', 'DOI': '10.1111/bph.15418', 'volume': '178', 'author': 'S Schloer', 'year': '2021', 'unstructured': 'Schloer S, Brunotte L, Mecate-Zambrano A, Zheng S, Tang J, Ludwig S, et ' 'al. Drug synergy of combinatory treatment with remdesivir and the ' 'repurposed drugs fluoxetine and itraconazole effectively impairs ' 'SARS-CoV-2 infection in vitro. Br J Pharm. 2021;178:2339–50.', 'journal-title': 'Br J Pharm'}, { 'key': '2004_CR45', 'doi-asserted-by': 'publisher', 'DOI': '10.1038/s41598-021-85049-0', 'volume': '11', 'author': 'M Zimniak', 'year': '2021', 'unstructured': 'Zimniak M, Kirschner L, Hilpert H, Geiger N, Danov O, Oberwinkler H, et ' 'al. The serotonin reuptake inhibitor Fluoxetine inhibits SARS-CoV-2 in ' 'human lung tissue. Sci Rep. 2021;11:5890.', 'journal-title': 'Sci Rep'}, { 'key': '2004_CR46', 'doi-asserted-by': 'publisher', 'first-page': '13623', 'DOI': '10.3390/ijms232113623', 'volume': '23', 'author': 'D Péricat', 'year': '2022', 'unstructured': 'Péricat D, Leon-Icaza SA, Sánchez-Rico M, Mühle C, Zoicas I, Schumacher ' 'F, et al. Antiviral and anti-inflammatory activities of fluoxetine in a ' 'SARS-CoV-2 infection mouse model. Int J Mol Sci. 2022;23:13623.', 'journal-title': 'Int J Mol Sci'}, { 'key': '2004_CR47', 'doi-asserted-by': 'publisher', 'first-page': '1357', 'DOI': '10.1016/S0140-6736(17)32802-7', 'volume': '391', 'author': 'A Cipriani', 'year': '2018', 'unstructured': 'Cipriani A, Furukawa TA, Salanti G, Chaimani A, Ogawa Y, Leucht S, et ' 'al. Comparative efficacy and acceptability of 21 antidepressant drugs ' 'for the acute treatment of adults with major depressive disorder: a ' 'systematic review and network meta-analysis. Lancet. 2018;391:1357–66.', 'journal-title': 'Lancet.'}, { 'key': '2004_CR48', 'doi-asserted-by': 'publisher', 'first-page': 'e000646', 'DOI': '10.1136/bmjresp-2020-000646', 'volume': '7', 'author': 'B Kirenga', 'year': '2020', 'unstructured': 'Kirenga B, Muttamba W, Kayongo A, Nsereko C, Siddharthan T, Luisba J, et ' 'al. Characteristics and outcomes of admitted patients infected with ' 'SARS-CoV-2 in Uganda. BMJ Open Resp Res. 2020;7:e000646.', 'journal-title': 'BMJ Open Resp Res'}, { 'key': '2004_CR49', 'unstructured': 'Jazz Pharmaceuticals. Luvox (fluvoxamine maleate)—full prescribing ' 'information. 2008. ' 'https://www.accessdata.fda.gov/drugsatfda_docs/label/2008/022235lbl.pdf.'}, { 'key': '2004_CR50', 'doi-asserted-by': 'publisher', 'first-page': 'ITC161', 'DOI': '10.7326/AITC202111160', 'volume': '174', 'author': 'TM Uyeki', 'year': '2021', 'unstructured': 'Uyeki TM. Influenza. Ann Intern Med. 2021;174:ITC161–76.', 'journal-title': 'Ann Intern Med'}, { 'key': '2004_CR51', 'doi-asserted-by': 'publisher', 'first-page': '1228', 'DOI': '10.1080/03610910902859574', 'volume': '38', 'author': 'PC Austin', 'year': '2009', 'unstructured': 'Austin PC. Using the standardized difference to compare the prevalence ' 'of a binary variable between two groups in observational research. ' 'Commun Stat Simul Comput. 2009;38:1228–34.', 'journal-title': 'Commun Stat Simul Comput'}, { 'key': '2004_CR52', 'doi-asserted-by': 'publisher', 'first-page': '550', 'DOI': '10.1097/00001648-200009000-00011', 'volume': '11', 'author': 'JM Robins', 'year': '2000', 'unstructured': 'Robins JM, Hernán MÁ, Brumback B. Marginal structural models and causal ' 'inference in epidemiology. Epidemiology. 2000;11:550–60.', 'journal-title': 'Epidemiology'}, { 'key': '2004_CR53', 'doi-asserted-by': 'publisher', 'first-page': 'e18', 'DOI': '10.1017/S2045796021000743', 'volume': '31', 'author': 'N Hoertel', 'year': '2022', 'unstructured': 'Hoertel N, Sánchez-Rico M, Gulbins E, Kornhuber J, Vernet R, Beeker N, ' 'et al. Association between benzodiazepine receptor agonist use and ' 'mortality in patients hospitalised for COVID-19: a multicentre ' 'observational study. Epidemiol Psychiatr Sci. 2022;31:e18.', 'journal-title': 'Epidemiol Psychiatr Sci'}, { 'key': '2004_CR54', 'doi-asserted-by': 'publisher', 'first-page': '221', 'DOI': '10.1007/s40261-021-01001-0', 'volume': '41', 'author': 'N Hoertel', 'year': '2021', 'unstructured': 'Hoertel N, Sánchez-Rico M, Vernet R, Jannot AS, Neuraz A, Blanco C, et ' 'al. Observational study of chlorpromazine in hospitalized patients with ' 'COVID-19. Clin Drug Investig. 2021;41:221–33.', 'journal-title': 'Clin Drug Investig'}, { 'key': '2004_CR55', 'doi-asserted-by': 'publisher', 'first-page': 'e0247122', 'DOI': '10.1371/journal.pone.0247122', 'volume': '16', 'author': 'N Hoertel', 'year': '2021', 'unstructured': 'Hoertel N, Sánchez-Rico M, Vernet R, Jannot AS, Neuraz A, Blanco C, et ' 'al. Observational study of haloperidol in hospitalized patients with ' 'COVID-19. PLoS ONE. 2021;16:e0247122.', 'journal-title': 'PLoS ONE'}, { 'key': '2004_CR56', 'doi-asserted-by': 'publisher', 'first-page': '139', 'DOI': '10.2307/3314608', 'volume': '9', 'author': 'B Efron', 'year': '1981', 'unstructured': 'Efron B. Nonparametric standard errors and confidence intervals. Can J ' 'Stat. 1981;9:139–58.', 'journal-title': 'Can J Stat'}, { 'key': '2004_CR57', 'unstructured': 'Kassambara A, Kosinski M, Biecek P. Survminer: Drawing Survival Curves ' 'Using “Ggplot2”. 2020. https://CRAN.R-project.org/package=survminer.'}, { 'key': '2004_CR58', 'doi-asserted-by': 'publisher', 'unstructured': 'Ho DE, Imai K, King G, Stuart EA. MatchIt: nonparametric preprocessing ' 'for parametric causal inference. J Stat Softw. 2011;42. ' 'https://doi.org/10.18637/jss.v042.i08.', 'DOI': '10.18637/jss.v042.i08'}, { 'key': '2004_CR59', 'doi-asserted-by': 'publisher', 'first-page': '51', 'DOI': '10.4103/2229-3485.173773', 'volume': '7', 'author': 'P Ranganathan', 'year': '2016', 'unstructured': 'Ranganathan P, Pramesh C, Aggarwal R. Common pitfalls in statistical ' 'analysis: absolute risk reduction, relative risk reduction, and number ' 'needed to treat. Perspect Clin Res. 2016;7:51.', 'journal-title': 'Perspect Clin Res'}, { 'key': '2004_CR60', 'unstructured': 'Yang Z. Nnt: the number needed to treat (NNT) for survival endpoint. ' '2020. https://CRAN.R-project.org/package=nnt.'}, { 'key': '2004_CR61', 'doi-asserted-by': 'crossref', 'unstructured': 'Therneau TM, Grambsch PM. Modeling survival data: extending the Cox ' 'model. Springer; New York, USA; 2000.', 'DOI': '10.1007/978-1-4757-3294-8'}, { 'key': '2004_CR62', 'doi-asserted-by': 'publisher', 'first-page': '515', 'DOI': '10.1093/biomet/81.3.515', 'volume': '81', 'author': 'PM Grambsch', 'year': '1994', 'unstructured': 'Grambsch PM, Therneau TM. Proportional hazards tests and diagnostics ' 'based on weighted residuals. Biometrika. 1994;81:515–26.', 'journal-title': 'Biometrika.'}, { 'key': '2004_CR63', 'unstructured': 'R Core Team. R: a language and environment for statistical computing. R ' 'Foundation for Statistical Computing. Auckland, New Zealand; 2022. ' 'https://www.R-project.org/.'}, { 'key': '2004_CR64', 'doi-asserted-by': 'publisher', 'first-page': 'e6', 'DOI': '10.1192/bjo.2021.1053', 'volume': '8', 'author': 'CL Clelland', 'year': '2021', 'unstructured': 'Clelland CL, Ramiah K, Steinberg L, Clelland JD. Analysis of the impact ' 'of antidepressants and other medications on COVID-19 infection risk in a ' 'chronic psychiatric in-patient cohort. BJPsych Open. 2021;8:e6.', 'journal-title': 'BJPsych Open'}, { 'key': '2004_CR65', 'doi-asserted-by': 'publisher', 'first-page': '111437', 'DOI': '10.1016/j.biopha.2021.111437', 'volume': '138', 'author': 'JF Creeden', 'year': '2021', 'unstructured': 'Creeden JF, Imami AS, Eby HM, Gillman C, Becker KN, Reigle J, et al. ' 'Fluoxetine as an anti-inflammatory therapy in SARS-CoV-2 infection. ' 'Biomed Pharmacother. 2021;138:111437.', 'journal-title': 'Biomed Pharmacother'}, { 'key': '2004_CR66', 'doi-asserted-by': 'publisher', 'first-page': 'e333', 'DOI': '10.1016/S2214-109X(21)00588-X', 'volume': '10', 'author': 'G Reis', 'year': '2022', 'unstructured': 'Reis G, Mills E. Fluvoxamine for the treatment of COVID-19—author’s ' 'reply. Lancet Glob Health. 2022;10:e333.', 'journal-title': 'Lancet Glob Health'}], 'container-title': 'Molecular Psychiatry', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://www.nature.com/articles/s41380-023-02004-3.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.nature.com/articles/s41380-023-02004-3', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.nature.com/articles/s41380-023-02004-3.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 3, 3]], 'date-time': '2023-03-03T10:05:59Z', 'timestamp': 1677837959000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.nature.com/articles/s41380-023-02004-3'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2023, 3, 3]]}, 'references-count': 66, 'alternative-id': ['2004'], 'URL': 'http://dx.doi.org/10.1038/s41380-023-02004-3', 'relation': {}, 'ISSN': ['1359-4184', '1476-5578'], 'subject': ['Cellular and Molecular Neuroscience', 'Psychiatry and Mental health', 'Molecular Biology'], 'container-title-short': 'Mol Psychiatry', 'published': {'date-parts': [[2023, 3, 3]]}, 'assertion': [ { 'value': '17 November 2022', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '8 February 2023', 'order': 2, 'name': 'revised', 'label': 'Revised', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '15 February 2023', 'order': 3, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '3 March 2023', 'order': 4, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': 'NH is an inventor on a patent application related to methods of treating ' 'COVID-19 (FIASMA antidepressants), filled by Assistance Publique-Hopitaux de ' 'Paris in France. The other authors have no conflicts of interest related to ' 'this work to declare.', 'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Competing interests'}}, { 'value': 'Compassionate use approval of fluvoxamine for the treatment of COVID-19 was ' 'obtained from the Ministry of Health of Uganda (clearance reference no. ' 'ADM.180/O1 dated 2nd January 2022). All patients were informed that this ' 'medication was under evaluation by health authorities. Patients willing to be ' 'treated with this medication gave verbal informed consent. All data used in ' 'this study were collected as part of routine care.', 'order': 2, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Ethical approval'}}]}