Effect of Antidepressants Use on Cancer Morbidity and Mortality: A Propensity Score-Matched Longitudinal Cohort Study

• Published in: Journal of affective disorders Vol. 387; p. 119554
• Main Authors: Ma, Yue, He, Jing, Li, Chen-yang, Liu, Fu-bin, Wang, Yao-gang, Song, Feng-ju
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.10.2025
• Subjects: Adult; Aged; Antidepressant; Antidepressive Agents - adverse effects; Antidepressive Agents - therapeutic use; Cancer morbidity; Cohort; Female; Humans; Longitudinal Studies; Male; Middle Aged; Mortality; Neoplasms - epidemiology; Neoplasms - mortality; Propensity Score; Prospective Studies; Psychiatric/Mental Health; Selective Serotonin Reuptake Inhibitors - adverse effects; Selective Serotonin Reuptake Inhibitors - therapeutic use; United Kingdom - epidemiology; United Kingdom; Antidepressant; Cancer morbidity; Propensity score; Cohort; Mortality
• ISSN: 0165-0327; 1573-2517; 1573-2517
• DOI: 10.1016/j.jad.2025.119554

To investigate the association between antidepressant use and cancer risk in a large prospective cohort. A prospective cohort study involving participants without cancer or cardiovascular disease at baseline in the UK Biobank. Antidepressant users were matched to non-users using propensity score matching (PSM). The primary outcomes included overall cancer morbidity and mortality, with site-specific cancer morbidity as a secondary outcome. The median follow-up was 13.6 years. Of the 421,529 participants, 26,796 were antidepressant users, and 394,733 were non-users. After 1:1 PSM, 26,372 matched pairs were identified. Antidepressant use was associated with a reduced risk of overall cancer morbidity (HR 0.89, 95 % CI 0.85–0.94), particularly for CRC (HR 0.75, 95 % CI 0.65–0.86), and a lower risk of cancer-related mortality (HR 0.91, 95 % CI 0.84–0.99) compared to nonusers. Among antidepressant subtypes, selective serotonin reuptake inhibitors (SSRIs) were associated with a lower risk of overall cancer morbidity, especially fluoxetine, citalopram, and sertraline. SSRIs were also associated with a reduced risk of cancer-related mortality, particularly 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. The use of antidepressants, particularly SSRIs, was associated with a lower risk of cancer morbidity and mortality, whereas the use of TCAs, such as amitriptyline, was linked to an increased risk of cancer-related mortality. Although causal relationships cannot be established, these findings should be interpreted with caution and warrant further investigation. •Antidepressant use is increasing worldwide and potential anti-cancer effects have been observed in vitro.•The use of SSRIs was associated with a lower risk of overall cancer morbidity and cancer-related mortality.•The use of TCAs, particularly amitriptyline, were related to a higher risk of mesothelioma, lung cancer, and cancer-related mortality.