Abstract 3593: Effect of regular antidepressants use on cancer morbidity and mortality: A propensity score matched cohort study

Abstract Background—Antidepressant use is rising globally and has shown potential anticancer properties in vitro, but findings from observational studies have been inconsistent. We aimed to investigate the association between regular antidepressant use and cancer risk in a large prospective cohort with long-term follow-up. Methods—A total of 421, 529 participants without cancer or cardiovascular disease at baseline were obtained from the UK Biobank, recruited between 2006 and 2010 from 22 assessment centres across the UK. Regular antidepressant users were matched to nonusers using propensity score matching (PSM), adjusting for 21 key covariates, including age, sex, race, socioeconomic status, lifestyle factors, and medical history. The primary outcomes were overall cancer morbidity and mortality, with site-specific cancer morbidity as a secondary outcome. The association between different antidepressant subtypes and cancer risk was also examined. Findings—The median follow-up was 13.6 years. Of the participants, 26, 796 were regular antidepressant users and 394, 733 were nonusers. After 1:1 PSM, 26, 372 matched pairs were identified. Regular antidepressant use was associated with a reduced risk of overall cancer morbidity (HR 0.83, 95% CI 0.79-0.88), particularly for colorectal cancer (HR 0.75, 95% CI 0.65-0.86), and lower cancer-related mortality (HR 0.91, 95% CI 0.84-0.99) compared with nonusers. Among antidepressant subtypes, selective serotonin reuptake inhibitors (SSRIs) were associated with a 17% reduced risk of overall cancer morbidity (HR 0.83, 95% CI 0.79-0.88), especially for fluoxetine, citalopram, and sertraline. SSRIs were also associated with a 23% reduced risk of cancer-related mortality (HR 0.77, 95% CI 0.70-0.85), particularly with fluoxetine and citalopram. However, tricyclic antidepressants (TCAs) were linked to an increased risk of cancer-related mortality (HR 1.19, 95% CI 1.07-1.32), especially for amitriptyline. Interpretation—These findings provide important evidence for the potential repurposing of antidepressants in cancer prevention and treatment. However, TCAs, such as amitriptyline, were associated with an increased risk, warranting caution. Further research is needed to confirm these findings. Citation Format: Jing He, Yue Ma, chenyang Li, Fubin Liu, Yaogang Wang, Fengju Song. Effect of regular antidepressants use on cancer morbidity and mortality: A propensity score matched cohort study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3593.