{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T12:21:35Z","timestamp":1777724495459,"version":"3.51.4"},"reference-count":14,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2024,4,30]],"date-time":"2024-04-30T00:00:00Z","timestamp":1714435200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"University of Virginia Strategic investment fund","award":["176"],"award-info":[{"award-number":["176"]}]},{"name":"NIH-","award":["R01DA054992"],"award-info":[{"award-number":["R01DA054992"]}]},{"name":"NIH--","award":["R01EY029799"],"award-info":[{"award-number":["R01EY029799"]}]},{"name":"NIH---","award":["R01EY031039"],"award-info":[{"award-number":["R01EY031039"]}]},{"name":"NIH----","award":["R01AG078892"],"award-info":[{"award-number":["R01AG078892"]}]},{"name":"NIH-----","award":["R01AG078892"],"award-info":[{"award-number":["R01AG078892"]}]},{"name":"NIH------","award":["R01AG082108"],"award-info":[{"award-number":["R01AG082108"]}]},{"name":"DuPont Guerry"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Investigative Medicine"],"published-print":{"date-parts":[[2024,8]]},"abstract":"<jats:p>Cisplatin use is often limited by its ototoxic side effects, which can lead to irreversible hearing loss. Preventing cisplatin-induced ototoxicity is crucial to improve patient outcomes. Fluoxetine and fluvoxamine, both selective serotonin reuptake inhibitors antidepressants, inhibit the NLR pyrin domain-containing protein 3 inflammasome, a potential therapeutic target for preventing ototoxicity. However, human studies have not evaluated if these antidepressants may protect against cisplatin-induced ototoxicity. The object of this study is to assess the association between fluoxetine or fluvoxamine use and incidence of hearing loss or tinnitus in a large cohort of patients receiving cisplatin chemotherapy. We use a retrospective cohort study within the U.S. Department of Veterans Affairs healthcare system. Adult patients with cancer who received cisplatin chemotherapy between 2000 and 2023 are included. Incidence of ototoxicity, defined by international classification of diseases revision 9-CM or international classification of diseases revision 10-CM diagnoses of hearing loss or tinnitus is compared between concurrent use of fluoxetine or fluvoxamine and cisplatin alone. A total of 20,552 patients were included. Of those, 489 received cisplatin and fluoxetine or fluvoxamine. After propensity score adjustment, the hazard of ototoxicity was lower in the group receiving fluoxetine or fluvoxamine compared to the group receiving cisplatin alone (HR\u2009=\u20090.62, 95% CI\u2009=\u2009(0.41\u20130.94)). Fluoxetine or fluvoxamine use may be associated with a reduced risk of cisplatin-induced ototoxicity. Randomized clinical trials are needed to confirm these findings and establish the efficacy of the medications in ototoxicity prevention. Further research is also warranted to investigate the potential mechanisms underlying this protective effect.<\/jats:p>","DOI":"10.1177\/10815589241247796","type":"journal-article","created":{"date-parts":[[2024,4,10]],"date-time":"2024-04-10T06:47:46Z","timestamp":1712731666000},"page":"579-586","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Fluoxetine, fluvoxamine, and hearing loss or tinnitus after cisplatin treatment: A retrospective cohort study"],"prefix":"10.1177","volume":"72","author":[{"given":"Joseph","family":"Magagnoli","sequence":"first","affiliation":[{"name":"Dorn Research Institute, Columbia VA Health Care System, Columbia, SC, USA"},{"name":"Department of Clinical Pharmacy and Outcomes Sciences, University of South Carolina College of Pharmacy, Columbia, SC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tammy H.","family":"Cummings","sequence":"additional","affiliation":[{"name":"Dorn Research Institute, Columbia VA Health Care System, Columbia, SC, USA"},{"name":"Department of Clinical Pharmacy and Outcomes Sciences, University of South Carolina College of Pharmacy, Columbia, SC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James W.","family":"Hardin","sequence":"additional","affiliation":[{"name":"Dorn Research Institute, Columbia VA Health Care System, Columbia, SC, USA"},{"name":"Department of Epidemiology and Biostatistics, University of South Carolina, Columbia, SC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. Scott","family":"Sutton","sequence":"additional","affiliation":[{"name":"Dorn Research Institute, Columbia VA Health Care System, Columbia, SC, USA"},{"name":"Department of Clinical Pharmacy and Outcomes Sciences, University of South Carolina College of Pharmacy, Columbia, SC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jayakrishna","family":"Ambati","sequence":"additional","affiliation":[{"name":"Center for Advanced Vision Science, University of Virginia School of Medicine, Charlottesville, VI, USA"},{"name":"Department of Ophthalmology, University of Virginia School of Medicine, Charlottesville, VI, USA"},{"name":"Department of Pathology, University of Virginia School of Medicine, Charlottesville, VI, USA"},{"name":"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2024,4,30]]},"reference":[{"key":"bibr1-10815589241247796","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2015.06.012"},{"key":"bibr2-10815589241247796","unstructured":"U.S. Food and Drug Administration. Prescribing information for cisplatin [online]. Silver Spring, MD: FDA, 1978, https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2019\/018057s089lbl.pdf (accessed 4 October 2023)."},{"key":"bibr3-10815589241247796","doi-asserted-by":"publisher","DOI":"10.1097\/00000421-199906000-00020"},{"key":"bibr4-10815589241247796","doi-asserted-by":"publisher","DOI":"10.1080\/14992027.2017.1417644"},{"key":"bibr5-10815589241247796","doi-asserted-by":"publisher","DOI":"10.1200\/OP.22.00710"},{"key":"bibr6-10815589241247796","unstructured":"U.S. Food and Drug Administration. FDA approves sodium thiosulfate to reduce the risk of ototoxicity associated with cisplatin in pediatric patients with localized, non-metastatic solid tumors [online]. Silver Spring, MD: FDA, 2019, https:\/\/www.fda.gov\/drugs\/resources-information-approved-drugs\/fda-approves-sodium-thiosulfate-reduce-risk-ototoxicity-associated-cisplatin-pediatric-patients (accessed 4 October 2023)."},{"key":"bibr7-10815589241247796","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01837-1"},{"key":"bibr8-10815589241247796","first-page":"196","volume":"10","author":"McCabe B. 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