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Mechanisms of action of fluvoxamine for COVID-19: a historical review

Hashimoto et al., Molecular Psychiatry, doi:10.1038/s41380-021-01432-3
Jan 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.
5,100+ studies for 109 treatments. c19early.org
Review of the potential mechanisms of action of fluvoxamine for COVID-19.
Reviews covering fluvoxamine for COVID-19 include1-7.
Hashimoto et al., 7 Jan 2022, peer-reviewed, 3 authors.
This PaperFluvoxamineAll
Mechanisms of action of fluvoxamine for COVID-19: a historical review
Yaeko Hashimoto, Takuji Suzuki, Kenji Hashimoto
Molecular Psychiatry, doi:10.1038/s41380-021-01432-3
The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) accelerates the discovery of prophylactic and therapeutic drugs for persons infected with the virus. Drug repurposing for the COVID-19 pandemic has received particular attention. Increasing clinical data suggest that antidepressant use in early-stage subjects with COVID-19 might be associated with a reduced risk of intubation or death. Among the antidepressants, fluvoxamine is the most attractive drug for mild to moderate subjects with COVID-19. In this article, we review the mechanisms of action (i.e., serotonin transporter, sigma-1 receptor, and acid sphingomyelinase) of fluvoxamine for COVID-19. Furthermore, we discuss a possible link between maternal COVID-19 infection and a risk for neuropsychiatric disorders (i.e., autism spectrum disorder and schizophrenia) in offspring.
AUTHOR CONTRIBUTIONS Y.H., T.S., and K.H. did the reference search and wrote the manuscript. Y.H. and K.H. prepared the figures and table. All authors approved the final manuscript. CONFLICT OF INTEREST Dr. Y. Hashimoto and Dr. T. Suzuki have no conflict of interest. Dr. K. Hashimoto is the inventor of filed patent applications on "The use of R-Ketamine in the treatment of psychiatric diseases", "(S)-norketamine and salt thereof as pharmaceutical", "R-Ketamine and derivative thereof as a prophylactic or therapeutic agent for neurodegeneration disease or recognition function disorder", "Preventive or therapeutic agent and pharmaceutical composition for inflammatory diseases or bone diseases", and "R-Ketamine and its derivatives as a preventive or therapeutic agent for a neurodevelopmental disorder" by the Chiba University. Dr. K. Hashimoto has also received speakers' honoraria, consultant fees, or research support from Abbott, Meiji Seika Pharma, Dainippon-Sumitomo, Taisho, Otsuka, Murakami Farm, and Perception Neuroscience. ADDITIONAL INFORMATION Correspondence and requests for materials should be addressed to Kenji Hashimoto. Reprints and permission information is available at http://www.nature.com/reprints Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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JAMA Pediatr. 2021;175:817–26.', 'journal-title': 'JAMA Pediatr'}, { 'key': '1432_CR109', 'doi-asserted-by': 'crossref', 'first-page': '2273', 'DOI': '10.1056/NEJMoa2104983', 'volume': '384', 'author': 'TT Shimabukuro', 'year': '2021', 'unstructured': 'Shimabukuro TT, Kim SY, Meyers TR, Moro PL, Oduyebo T, Panagiotakopoulos ' 'L, et al. Preliminary findings of mRNA Covid-19 vaccine safety in ' 'pregnant persons. N. Eng J Med. 2021;384:2273–82.', 'journal-title': 'N. Eng J Med'}, { 'key': '1432_CR110', 'volume': '8', 'author': 'A Matsuura', 'year': '2018', 'unstructured': 'Matsuura A, Ishima T, Fujita Y, Iwayama Y, Hasegawa S, Kawahara-Miki R, ' 'et al. Dietary glucoraphanin prevents the onset of psychosis in the ' 'adult offspring after maternal immune activation. Sci Rep. 2018;8:2158.', 'journal-title': 'Sci Rep.'}, { 'key': '1432_CR111', 'doi-asserted-by': 'crossref', 'first-page': '268', 'DOI': '10.1002/npr2.12112', 'volume': '40', 'author': 'Y Fujita', 'year': '2020', 'unstructured': 'Fujita Y, Fujita A, Ishima T, Hirai A, Suzuki S, Suganuma H, et al. ' 'Dietary intake of glucoraphanin during pregnancy and lactation prevents ' 'the behavioral abnormalities in the offspring after maternal immune ' 'activation. Neuropsychopharmacol Rep. 2020;40:268–74.', 'journal-title': 'Neuropsychopharmacol Rep.'}, { 'key': '1432_CR112', 'doi-asserted-by': 'crossref', 'DOI': '10.1007/s11920-019-1063-7', 'volume': '21', 'author': 'K Hashimoto', 'year': '2019', 'unstructured': 'Hashimoto K. Recent advances in the early intervention in schizophrenia: ' 'future direction from preclinical findings. Curr Psychiatry Rep. 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Pediatr Investig. 2020;4:118–26.', 'journal-title': 'Pediatr Investig'}, { 'key': '1432_CR115', 'doi-asserted-by': 'crossref', 'first-page': '100297.', 'DOI': '10.1016/j.bbih.2021.100297', 'volume': '16', 'author': 'B Lins', 'year': '2021', 'unstructured': 'Lins B. Maternal immune activation as a risk factor for psychiatric ' 'illness in the context of the SARS-CoV-2 pandemic. Brain Behav Immun ' 'Health. 2021;16:100297.', 'journal-title': 'Brain Behav Immun Health'}, { 'key': '1432_CR116', 'doi-asserted-by': 'crossref', 'first-page': '1', 'DOI': '10.1016/j.clnesp.2021.04.019', 'volume': '43', 'author': 'MC Hoffman', 'year': '2021', 'unstructured': 'Hoffman MC, Freedman R, Law AJ, Clark AM, Hunter SK. Maternal nutrients ' 'and effects of gestational COVID-19 infection on fetal brain ' 'development. Clin Nutr ESPEN. 2021;43:1–8.', 'journal-title': 'Clin Nutr ESPEN'}, { 'key': '1432_CR117', 'doi-asserted-by': 'crossref', 'first-page': '161', 'DOI': '10.1016/j.eurpsy.2017.06.001', 'volume': '45', 'author': 'S Andalib', 'year': '2017', 'unstructured': 'Andalib S, Emamhadi MR, Yousefzadeh-Chabok S, Shakouri SK, ' 'Høilund-Carlsen PF, Vafaee MS, et al. Maternal SSRI exposure increases ' 'the risk of autistic offspring: a meta-analysis and systematic review. ' 'Eur Psychiatry. 2017;45:161–6.', 'journal-title': 'Eur Psychiatry'}, { 'key': '1432_CR118', 'doi-asserted-by': 'crossref', 'first-page': '555', 'DOI': '10.1001/jamapediatrics.2017.0124', 'volume': '171', 'author': 'A Mezzacappa', 'year': '2017', 'unstructured': 'Mezzacappa A, Lasica PA, Gianfagna F, Cazas O, Hardy P, Falissard B, et ' 'al. Risk for autism spectrum disorders according to period of prenatal ' 'antidepressant exposure: a systematic review and meta-analysis. JAMA ' 'Pediatr. 2017;171:555–63.', 'journal-title': 'JAMA Pediatr'}, { 'key': '1432_CR119', 'doi-asserted-by': 'crossref', 'first-page': '1553', 'DOI': '10.1001/jama.2017.3413', 'volume': '317', 'author': 'AC Sujan', 'year': '2017', 'unstructured': 'Sujan AC, Rickert ME, Öberg AS, Quinn PD, Hernández-Díaz S, Almqvist C, ' 'et al. Associations of maternal antidepressant use during the first ' 'trimester of pregnancy with preterm birth, small for gestational age, ' 'autism spectrum disorder, and attention-deficit/hyperactivity disorder ' 'in offspring. JAMA. 2017;317:1553–62.', 'journal-title': 'JAMA'}, { 'key': '1432_CR120', 'doi-asserted-by': 'crossref', 'first-page': '1241', 'DOI': '10.1001/jamapsychiatry.2019.2859', 'volume': '76', 'author': 'E Dragioti', 'year': '2019', 'unstructured': 'Dragioti E, Solmi M, Favaro A, Fusar-Poli P, Dazzan P, Thompson T, et ' 'al. Association of antidepressant use with adverse health outcomes: a ' 'systematic umbrella review. JAMA Psychiatry. 2019;76:1241–55.', 'journal-title': 'JAMA Psychiatry'}, { 'key': '1432_CR121', 'doi-asserted-by': 'crossref', 'first-page': '506', 'DOI': '10.1176/appi.ajp.2020.18070766', 'volume': '177', 'author': 'ML Vega', 'year': '2020', 'unstructured': 'Vega ML, Newport GC, Bozhdaraj D, Saltz SB, Nemeroff CB, Newport DJ. ' 'Implementation of advanced methods for reproductive pharmacovigilance in ' 'autism: a meta-analysis of the effects of prenatal antidepressant ' 'exposure. Am J Psychiatry. 2020;177:506–17.', 'journal-title': 'Am J Psychiatry'}, { 'key': '1432_CR122', 'doi-asserted-by': 'crossref', 'first-page': '113912', 'DOI': '10.1016/j.psychres.2021.113912', 'volume': '300', 'author': 'LM Tomfohr-Madsen', 'year': '2021', 'unstructured': 'Tomfohr-Madsen LM, Racine N, Giesbrecht GF, Lebel C, Madigan S. ' 'Depression and anxiety in pregnancy during COVID-19: A rapid review and ' 'meta-analysis. Psychiatry Res. 2021;300:113912.', 'journal-title': 'Psychiatry Res'}, { 'key': '1432_CR123', 'first-page': 'CD013825', 'volume': '9', 'author': 'N Kreuzberger', 'year': '2021', 'unstructured': 'Kreuzberger N, Hirsch C, Chai KL, Tomlinson E, Khosravi Z, Popp M, et ' 'al. SARS-CoV-2-neutralising monoclonal antibodies for treatment of ' 'COVID-19. Cochrane Database Syst Rev. 2021;9:CD013825.', 'journal-title': 'Cochrane Database Syst Rev'}, { 'key': '1432_CR124', 'doi-asserted-by': 'crossref', 'first-page': 'n2422.', 'DOI': '10.1136/bmj.n2422', 'volume': '375', 'author': 'E Mahase', 'year': '2021', 'unstructured': 'Mahase E. Covid-19: molnupiravir reduces risk of hospital admission or ' 'death by 50% in patients at risk, MSD reports. BMJ. 2021;375:n2422.', 'journal-title': 'BMJ'}, { 'key': '1432_CR125', 'doi-asserted-by': 'publisher', 'unstructured': 'Sidik SM. Common antidepressant slashes risk of COVID-19 death. Nature. ' '2021. https://doi.org/10.1038/d41586-021-02988-4.', 'DOI': '10.1038/d41586-021-02988-4'}], 'container-title': ['Molecular Psychiatry'], 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://www.nature.com/articles/s41380-021-01432-3.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.nature.com/articles/s41380-021-01432-3', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.nature.com/articles/s41380-021-01432-3.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2022, 1, 7]], 'date-time': '2022-01-07T11:06:11Z', 'timestamp': 1641553571000}, 'score': 1, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2022, 1, 7]]}, 'references-count': 125, 'alternative-id': ['1432'], 'URL': 'http://dx.doi.org/10.1038/s41380-021-01432-3', 'relation': {}, 'ISSN': ['1359-4184', '1476-5578'], 'issn-type': [{'value': '1359-4184', 'type': 'print'}, {'value': '1476-5578', 'type': 'electronic'}], 'subject': ['Cellular and Molecular Neuroscience', 'Psychiatry and Mental health', 'Molecular Biology'], 'published': {'date-parts': [[2022, 1, 7]]}, 'assertion': [ { 'value': '4 October 2021', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '13 December 2021', 'order': 2, 'name': 'revised', 'label': 'Revised', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '23 December 2021', 'order': 3, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '7 January 2022', 'order': 4, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': 'Dr. Y. Hashimoto and Dr. T. Suzuki have no conflict of interest. Dr. K. ' 'Hashimoto is the inventor of filed patent applications on “The use of ' '<i>R</i>-Ketamine in the treatment of psychiatric diseases”, ' '“(<i>S</i>)-norketamine and salt thereof as pharmaceutical”, “<i>R</i>-Ketamine ' 'and derivative thereof as a prophylactic or therapeutic agent for ' 'neurodegeneration disease or recognition function disorder”, “Preventive or ' 'therapeutic agent and pharmaceutical composition for inflammatory diseases or ' 'bone diseases”, and “<i>R</i>-Ketamine and its derivatives as a preventive or ' 'therapeutic agent for a neurodevelopmental disorder” by the Chiba University. ' 'Dr. K. Hashimoto has also received speakers’ honoraria, consultant fees, or ' 'research support from Abbott, Meiji Seika Pharma, Dainippon-Sumitomo, Taisho, ' 'Otsuka, Murakami Farm, and Perception Neuroscience.', 'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Conflict of interest'}}, { 'value': 'This content has been made available to all.', 'name': 'free', 'label': 'Free to read'}]}
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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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