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

Objective: To investigate the association between antidepressant use and cancer risk in a large prospective cohort.

Methods: 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.

Results: 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.

Conclusion: 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.