Abstract
(1) Background: The potential of old drugs in novel indications is being greatly valued. We propose a triple-model study involving population-based, cell, and animal studies to investigate the effects of risperidone, a type of second-generation antipsychotic (SGA) drug, on colorectal cancer. (2) Methods: We used data from Taiwan’s National Health Insurance Research Database between 1997 and 2013 to compare 101,989 patients with colorectal cancer and 101,989 controls. Conditional logistic regression analyses were used to explore the association between SGA exposure and the risk of colorectal cancer. The following bench studies were performed to evaluate the findings of the population-based study. (3) Results: We found that SGAs had been less commonly used in colorectal cancer patients than in controls. The colorectal cancer risk was reduced with an increase in the cumulative defined daily dose (cDDD) of SGAs. The adjusted odds ratio of antipsychotic use for cDDD days was 0.32 (95% CI: 0.25–0.42). Risperidone exhibited the most prominent tumor inhibition effect in a cell screen study. Bench data revealed that risperidone significantly induced apoptosis and elevated intracellular ROS in human SW480 cells and suppressed the proliferation of the xenografted SW480 tumor in nude mice. (4) Conclusion: This triple-model study demonstrates the association between risperidone usage and a lower risk of colorectal cancer.
Highlights
Investigation of the treatment potential of old drugs in novel indications is currently encouraged through the application of existing health information data (e.g., National Health Insurance [NHI]records) because the long-term real-world data readily provides established effect and safety records [1]further validation is often required because of the limitations of observational data, those from routine sources, including unmeasured confounding factors
Researchers have been interested in the potential beneficial effects of antipsychotic agents on cancer risk because of the reduced risk of certain cancers, prostate and colorectal cancer, reported in patients with schizophrenia [3,4,5,6] despite the substantial wider health disadvantages described in this population [7]
We propose a triple-model study comprising a nationwide population-based case–control study, a cell study, and an animal study to assess the role of second-generation antipsychotics (SGAs) on the risk of colorectal cancer and identify the drug with the greatest potential
Summary
Investigation of the treatment potential of old drugs in novel indications is currently encouraged through the application of existing health information data (e.g., National Health Insurance [NHI]records) because the long-term real-world data readily provides established effect and safety records [1]further validation is often required because of the limitations of observational data, those from routine sources, including unmeasured confounding factors. Researchers have been interested in the potential beneficial effects of antipsychotic agents on cancer risk because of the reduced risk of certain cancers, prostate and colorectal cancer, reported in patients with schizophrenia [3,4,5,6] despite the substantial wider health disadvantages described in this population [7]. No other population-based study has evaluated the risk of colorectal cancer among users of antipsychotics since the Danish study published in 2006, and associations with new generations of antipsychotics are unknown. We propose a triple-model study comprising a nationwide population-based case–control study, a cell study, and an animal study to assess the role of second-generation antipsychotics (SGAs) on the risk of colorectal cancer and identify the drug with the greatest potential.
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