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This has intensified concern about possible genotoxicity and DNA damage. Citalopram is emphasized because it has the most extensive and consistently positive in\u00a0vivo genotoxicity evidence among SSRIs, particularly in rodent comet and micronucleus endpoints. This review summarizes genotoxicity data for SSRIs, focusing on citalopram, across in\u00a0vitro assays, animal studies, human biomonitoring, and environmental research. We briefly define mutagenicity and clastogenic and aneugenic effects, describe major DNA lesions, and review commonly applied methods: comet, micronucleus, and chromosomal aberration tests, plus biomarker approaches such as \u03b3H2AX and measures of oxidative DNA damage. Potential off\u2010target mechanisms are considered in light of SSRI pharmacology and pharmacokinetics, including direct DNA interactions, mitochondrial dysfunction, reactive oxygen species generation, and disruption of chromosome segregation. Comparative findings indicate that citalopram and fluoxetine show the most consistent experimental genotoxic signals, whereas paroxetine and escitalopram are less frequently implicated. For citalopram, rodent studies report DNA strand breaks, combined clastogenic\/aneugenic effects in bone marrow, germ cell DNA damage, and reproductive toxicity, with additional positive findings in non\u2010mammalian models. Human studies are few and provide mixed, largely indirect evidence. Work suggests antioxidants can reduce SSRI\u2010related oxidative stress and DNA damage in some models. Environmental studies raise concern for aquatic organisms. Overall, citalopram shows genuine experimental genotoxic potential, but clinical relevance in humans remains uncertain and warrants robust longitudinal investigation and careful risk\u2013benefit assessment in practice.<\/jats:p>","DOI":"10.1002\/jat.70099","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T23:05:19Z","timestamp":1770851119000},"page":"1417-1432","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genotoxicity and DNA Damage in Long\u2010Term SSRI Therapy: A Review Across SSRIs With Citalopram as a Case Study"],"prefix":"10.1002","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1279-9564","authenticated-orcid":false,"given":"Emadeldin\u00a0M.","family":"Kamel","sequence":"first","affiliation":[{"name":"Chemistry Department, Faculty of Science Beni\u2010Suef University  Beni\u2010Suef Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sally\u00a0Mostafa","family":"Khadrawy","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science Imam Mohammad Ibn Saud Islamic University (IMSIU)  Riyadh Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nour\u00a0Y.\u00a0S.","family":"Yassin","sequence":"additional","affiliation":[{"name":"Physiology Division, Zoology Department, Faculty of Science Beni\u2010Suef University  Beni\u2010Suef Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5080-0933","authenticated-orcid":false,"given":"Noha\u00a0A.","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Physiology Division, Zoology Department, Faculty of Science Beni\u2010Suef University  Beni\u2010Suef Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,11]]},"reference":[{"key":"e_1_2_18_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13319"},{"key":"e_1_2_18_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-55035-6_8"},{"key":"e_1_2_18_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/0269881119874461"},{"key":"e_1_2_18_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-020-05550-8"},{"key":"e_1_2_18_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/10520295.2023.2233417"},{"key":"e_1_2_18_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyab086"},{"key":"e_1_2_18_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1201023"},{"key":"e_1_2_18_9_1","doi-asserted-by":"publisher","DOI":"10.31351\/vol30iss1pp81-90"},{"key":"e_1_2_18_10_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-199426030-00004"},{"key":"e_1_2_18_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-016-0338-3"},{"key":"e_1_2_18_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-016-0985-3"},{"key":"e_1_2_18_13_1","doi-asserted-by":"publisher","DOI":"10.4103\/1008-682X.192637"},{"key":"e_1_2_18_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.2859"},{"key":"e_1_2_18_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2012.11.051"},{"key":"e_1_2_18_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2023.119573"},{"key":"e_1_2_18_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19040970"},{"key":"e_1_2_18_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcpt.12095"},{"key":"e_1_2_18_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004850-199603001-00002"},{"key":"e_1_2_18_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mrrev.2011.11.002"},{"key":"e_1_2_18_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemosphere.2011.03.027"},{"key":"e_1_2_18_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2021.05.005"},{"key":"e_1_2_18_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1383-5718(98)00028-X"},{"key":"e_1_2_18_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.70168"},{"key":"e_1_2_18_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-006-9194-8"},{"key":"e_1_2_18_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0924-977X(01)00101-8"},{"key":"e_1_2_18_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14205110"},{"key":"e_1_2_18_28_1","doi-asserted-by":"publisher","DOI":"10.1159\/000447034"},{"key":"e_1_2_18_29_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.f288"},{"key":"e_1_2_18_30_1","doi-asserted-by":"crossref","unstructured":"Cavanah L. 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