The Association between Selective Serotonin Reuptake Inhibitors (SSRIs) Use and the Risk of Bladder Cancer: A Nationwide Population-Based Cohort Study

Background: Past studies suggest mixed associations between selective serotonin reuptake inhibitor (SSRI) prescription and carcinogenic risk. There is no epidemiological study reporting on the association between SSRI use and the incidence of bladder cancer. The aim of this study is to determine whether SSRI use influences the risk of bladder cancer. Methods: We conducted a nationwide retrospective cohort study by Taiwan's National Health Insurance Research Database from January 1, 1997 to December 31, 2013. 192,392 SSRI prescribed individuals were randomly matched 1 to 1 with 191,786 individuals who had never received any SSRIs by propensity scores match. The Cox Proportional Hazard models were conducted to examine the risk of bladder cancer between individuals prescribed SSRIs and individuals not prescribed SSRIs. Results: SSRIs were associated with significant reduced risk of bladder cancer with 0.5, 1, and 2 year induction periods (adjusted hazard ratio (aHR) = 0.86, 95% CI (confidence interval) = 0.76-0.98, aHR = 0.85, 95% CI = 0.75-0.97, and aHR = 0.77, 95% CI = 0.66-0.89). When examining the effect of specific SSRI, there was significantly lower risk of bladder cancer in individuals prescribed fluoxetine (6 month induction period: aHR = 0.78, 95% CI = 0.65-0.93; 1 year induction period: aHR = 0.78, 95% CI = 0.65-0.94; 2 year induction period: aHR = 0.73, 95% CI = 0.60-0.89), paroxetine (6 month induction period: aHR = 0.78, 95% CI = 0.61-0.99; 1 year induction period: aHR = 0.79, 95% CI = 0.61-1.01; 2 year induction period: aHR = 0.72, 95% CI = 0.54-0.95), and citalopram (6 month induction period: aHR = 0.74, 95% CI = 0.53-1.03; 1 year induction period: aHR = 0.70, 95% CI = 0.50-0.99; 2 year induction period: aHR = 0.60, 95% CI = 0.41-0.88). Conclusions: Individuals prescribed fluoxetine, paroxetine, or citalopram had a reduced risk of bladder cancer in this large, cross-national database.