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

DOI record: { "DOI": "10.1038/s41380-023-02004-3", "ISSN": [ "1359-4184", "1476-5578" ], "URL": "http://dx.doi.org/10.1038/s41380-023-02004-3", "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 = 37.0); women, 52.2%]. Fluvoxamine use was significantly associated with reduced mortality [AHR = 0.32; 95% CI = 0.19–0.53; <jats:italic>p</jats:italic> &lt; 0.001, NNT = 4.46] and with increased complete symptom resolution [AOR = 2.56; 95% CI = 1.53–5.51; <jats:italic>p</jats:italic> &lt; 0.001, NNT = 4.44]. 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> = 0.32]. There was a trend toward greater side effects with fluvoxamine (7.45% versus 3.15%; SMD = 0.21; <jats:italic>χ</jats:italic><jats:sup>2</jats:sup> = 3.46, <jats:italic>p</jats:italic> = 0.06), 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>", "alternative-id": [ "2004" ], "assertion": [ { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Received", "name": "received", "order": 1, "value": "17 November 2022" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Revised", "name": "revised", "order": 2, "value": "8 February 2023" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "Accepted", "name": "accepted", "order": 3, "value": "15 February 2023" }, { "group": { "label": "Article History", "name": "ArticleHistory" }, "label": "First Online", "name": "first_online", "order": 4, "value": "3 March 2023" }, { "group": { "label": "Competing interests", "name": "EthicsHeading" }, "name": "Ethics", "order": 1, "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." }, { "group": { "label": "Ethical approval", "name": "EthicsHeading" }, "name": "Ethics", "order": 2, "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." } ], "author": [ { "affiliation": [], "family": "Kirenga", "given": "Bruce J.", "sequence": "first" }, { "ORCID": "http://orcid.org/0000-0002-9423-2472", "affiliation": [], "authenticated-orcid": false, "family": "Mugenyi", "given": "Levicatus", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-1121-8641", "affiliation": [], "authenticated-orcid": false, "family": "Sánchez-Rico", "given": "Marina", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0001-6593-8727", "affiliation": [], "authenticated-orcid": false, "family": "Kyobe", "given": "Henry", "sequence": "additional" }, { "affiliation": [], "family": "Muttamba", "given": "Winters", "sequence": "additional" }, { "affiliation": [], "family": "Mugume", "given": "Raymond", "sequence": "additional" }, { "affiliation": [], "family": "Mwesigwa", "given": "Eliya", "sequence": "additional" }, { "affiliation": [], "family": "Kalimo", "given": "Ezra", "sequence": "additional" }, { "affiliation": [], "family": "Nyombi", "given": "Vicky", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0002-4535-1694", "affiliation": [], "authenticated-orcid": false, "family": "Segawa", "given": "Ivan", "sequence": "additional" }, { "affiliation": [], "family": "Namakula", "given": "Loryndah Olive", "sequence": "additional" }, { "affiliation": [], "family": "Sekibira", "given": "Rogers", "sequence": "additional" }, { "affiliation": [], "family": "Kabweru", "given": "Wilberforce", "sequence": "additional" }, { "affiliation": [], "family": "Byanyima", "given": "Rosemary", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0003-3159-4318", "affiliation": [], "authenticated-orcid": false, "family": "Aanyu", "given": "Hellen", "sequence": "additional" }, { "ORCID": "http://orcid.org/0000-0003-0757-1968", "affiliation": [], "authenticated-orcid": false, "family": "Byakika-Kibwika", "given": "Pauline", "sequence": "additional" }, { "affiliation": [], "family": "Mwebesa", "given": "Henry G.", "sequence": "additional" }, { "affiliation": [], "family": "Hoertel", "given": "Nicolas", "sequence": "additional" }, { "affiliation": [], "family": "Bazeyo", "given": "William", "sequence": "additional" } ], "container-title": "Molecular Psychiatry", "container-title-short": "Mol Psychiatry", "content-domain": { "crossmark-restriction": false, "domain": [ "link.springer.com" ] }, "created": { "date-parts": [ [ 2023, 3, 3 ] ], "date-time": "2023-03-03T09:02:28Z", "timestamp": 1677834148000 }, "deposited": { "date-parts": [ [ 2023, 3, 3 ] ], "date-time": "2023-03-03T10:05:59Z", "timestamp": 1677837959000 }, "funder": [ { "name": "Government of Uganda through Makerere University Research and Innovations Fund" } ], "indexed": { "date-parts": [ [ 2023, 3, 4 ] ], "date-time": "2023-03-04T05:44:07Z", "timestamp": 1677908647897 }, "is-referenced-by-count": 0, "issued": { "date-parts": [ [ 2023, 3, 3 ] ] }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "tdm", "delay-in-days": 0, "start": { "date-parts": [ [ 2023, 3, 3 ] ], "date-time": "2023-03-03T00:00:00Z", "timestamp": 1677801600000 } }, { "URL": "https://creativecommons.org/licenses/by/4.0", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2023, 3, 3 ] ], "date-time": "2023-03-03T00:00:00Z", "timestamp": 1677801600000 } } ], "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" } ], "member": "297", "original-title": [], "prefix": "10.1038", "published": { "date-parts": [ [ 2023, 3, 3 ] ] }, "published-online": { "date-parts": [ [ 2023, 3, 3 ] ] }, "publisher": "Springer Science and Business Media LLC", "reference": [ { "DOI": "10.1080/10408363.2020.1783198", "author": "M Ciotti", "doi-asserted-by": "publisher", "first-page": "365", "journal-title": "Crit Rev Clin Lab Sci", "key": "2004_CR1", "unstructured": "Ciotti M, Ciccozzi M, Terrinoni A, Jiang WC, Wang CB, Bernardini S. 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