Association Between Antipsychotic Agents and Risk of Lung Cancer: a Nested Case‐control Study

Dear Editor, Antipsychotics are a class of psychotropic medication primarily used for the treatment of schizophrenia and a range of other psychotic disorders. They are antagonists of multiple receptors, such as dopamine D1, dopamine D2, serotonin 5HT2A, and serotonin 5HT1A receptors. Serotonin antagonists have been identified as growthinhibiting agents in cancer cells, and they not only inhibit the growth of cancer cells but may also induce apoptosis in these cells [1]. Several studies have examined the association between antipsychotics and certain cancers, but the relationship between antipsychotics and lung cancer remains largely unknown. Here, we conducted a population-based nested casecontrol study, consisting of 38,318 lung cancer cases diagnosed from November 2011 to December 2019, and matched 191,590 population controls. Detailed descriptions of the study can be found in the Supplementary Materials and Methods section, Supplementary Table S1-S3, and Supplementary Figure S1. Briefly, exposure to antipsychotics was obtained from medication records and medical insurance databases. The exposure level was measured by olanzapine equivalent doses (OEDs). The odds ratios (ORs) for lung cancer associated with antipsychotics were estimated using the conditional logistic regression models. The effects of different classes of antipsychotics and individual antipsychotics on lung cancer risk were also assessed. The restricted cubic spline (RCS) with 3 knots was used to fit the nonlinear association between antipsychotics and lung cancer risk, and ANOVA for the nonlinearity test. We also conducted three sensitivity analyses to test the robustness of the main findings. The median age was 66 [inter quartile range (IQR), 5974] years in the entire cohort, and 60.09% of the study subjects were males. A total of 1077 subjects (0.47%) had