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Tricyclic antidepressants, such as amitriptyline, are the most researched and have shown significant gastroprotective effects, reducing ulcer size and severity, and inhibiting NOX2 and NOX4 (enzymes from the NADPH oxidase family) expression in gastric mucosa. Selective serotonin reuptake inhibitors also exhibit gastroprotective effects. Fluoxetine decreased ulcer size in a stress and indomethacin model while increasing antioxidant production and decreasing inflammation in indomethacin-induced ulcers, but one study found that fluoxetine had a greater gastroprotective effect in male rodents than in females, highlighting the need for further research on sex differences. Mirtazapine and duloxetine have also shown gastroprotective benefits. Mirtazapine reduced ulcer size in an indomethacin model. In a stress and indomethacin model, duloxetine reduced ulcer size while also decreasing NOX1 and NOX4 expression. The mechanisms underlying the gastroprotective effects of antidepressants involve peripheral reduction of mucosal oxidative stress and central modulation of vagal stimulus and an increase in noradrenergic and serotonergic neurotransmission.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Overall, the trials examined show that antidepressants are effective in preventing ulcers and may be useful in protecting against gastric ulcer development, especially in people with depression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10787-026-02240-3","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T15:41:40Z","timestamp":1776872500000},"page":"2889-2905","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Protective effects of antidepressants against ulcerogenic agents: insights from nonclinical studies"],"prefix":"10.1007","volume":"34","author":[{"given":"Caroline","family":"Stringari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heloisa","family":"Stringari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiago Farias","family":"de Queiroz e Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caio Henrique","family":"Willrich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa Mota","family":"da Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"2240_CR1","first-page":"25","volume":"16","author":"AR Abdel-Hamed","year":"2022","unstructured":"Abdel-Hamed AR et al (2022) Antisecretory and antioxidative effects of the antidepressants fluvoxamine and mirtazapine on water immersion stress and pyloric ligation-induced gastric ulcer in rats. 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