ANTIPSYCHOTIC MEDICATIONS AND RISK OF ALL-CAUSE, NATURAL, AND SUICIDE MORTALITY IN PATIENTS WITH SCHIZOPHRENIA: A NATIONWIDE COHORT STUDY

Abstract Background Antipsychotic medications are indicated for the treatment of schizophrenia, and clozapine is indicated as the last-line drug for patients with refractory schizophrenia due to its side effects. Aims & Objects This study included an Asian schizophrenia population and investigated the effect of antipsychotic medications and clozapine on the risks of all-cause, natural, and suicide mortality. Method This study included a large-scale schizophrenia inpatient cohort derived from the National Health Insurance Research Database from January 1, 2001, to December 31, 2019 (n = 43,025). Of them, we selected those who received clozapine (clozapine cohort, n = 5800). From those who never used clozapine, we selected two individuals for each patient in the clozapine cohort by matching by age, sex, and the year of the index date (ratio: 1:2, control cohort, n = 11,583). The clozapine and nonclozapine control cohorts together were defined as the study cohort (n = 17,383). Multivariate Cox proportional- hazards regression with a time-dependent model was performed to investigate the effect of individual antipsychotic agents on mortality. Results All individual first-generation antipsychotics were not associated with mortality risk. However, most individual second-generation antipsychotics exerted protective effects against all-cause and natural mortality. Furthermore, only clozapine and risperidone were significantly associated with a low risk of suicide mortality. Only clozapine exhibited a dose- dependent relationship with all-cause, natural, and suicide mortality. Discussion & Conclusion This study provides robust evidence supporting the strong protective effect of clozapine on all-cause, suicide, and natural mortality risks in an Asian population. Under close monitoring, clozapine use can be advantageous in patients with schizophrenia who are at a high risk of suicide. References Kane, J., Honigfeld, G., Singer, J., Meltzer, H., 1988. Clozapine for the treatment-resistant schizophrenic. A double-blind comparison with chlorpromazine. Arch Gen Psychiatry 45(9), 789-796. Kuo, C.J., Yang, S.Y., Liao, Y.T., Chen, W.J., Lee, W.C., Shau, W.Y., Chang, Y.T., Tsai, S.Y., Chen, C.C., 2013. Second-generation antipsychotic medications and risk of pneumonia in schizophrenia. Schizophr Bull 39(3), 648-657. Chen, P.H.,Tsai, S.Y., Chen, P.Y., Pan, C.H., Su, S.S., Chen, C.C., Kuo, C.J., 2023. Mood stabilizers and risk of all-cause, natural, and suicide mortality in bipolar disorder: A nationwide cohort study. Acta Psychiatr Scand 147(3), 234-247. Tiihonen, J., Lonnqvist, J., Wahlbeck, K., Klaukka, T., Niskanen, L., Tanskanen, A., Haukka, J., 2009. 11- year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet 374(9690), 620-627. Chen WY, Chen PH, Pan CH, Su SS, Tsai SS, Chen CC, Kuo CJ*. Clozapine and its Protective Effect on All- Cause, Natural, and Suicide Mortality in Patients with Schizophrenia: A Nationwide Cohort Study in Taiwan. Schizophrenia Research 2023 Jul 19;S0920-9964(23)00240-2. doi: 10.1016/j.schres.2023.07.014.