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Purpose:  To examine the effects of risperidone, an atypical antipsychotic agent, on gastric cancer.   Methods:  A triangulation method comprising bench studies, including cell and animal experiments, and a retrospective cohort study, was subsequently performed.   Results:  The bench study indicated that risperidone exerted more prominent tumor inhibition effects than other atypical antipsychotics on the proliferation of KATO-III cells, a human gastric cancer cell line. Significant and dose-dependent cell viability was observed in Hs27 cells (control cells) in the presence of risperidone compared with in KATO-III cells. Both  in vivo  and  in vitro  results indicated that risperidone significantly inhibited the proliferation of KATO-III cells by inducing ROS and apoptosis, and that it suppressed the growth of xenografted KATO-III tumors in nude mice. In addition, the population-based cohort study found that risperidone users had reduced risks of gastric cancer compared with non-users, with lowered adjusted hazard ratios (HRs) for two induction periods (HR = 0.75; 95% confidence interval [CI] 0.68–0.83 for the one-year induction period, and HR = 0.68; 95% CI 0.61–0.75 for the two-year induction period).   Conclusion:  The findings are consistent with anticancer effects associated with risperidone, but further research and evaluations are warranted.

Association of Risperidone With Gastric Cancer: Triangulation Method From Cell Study, Animal Study, and Cohort Study