ANTIPSYCHOTIC MEDICATIONS AND RISK OF ALL-CAUSE, NATURAL, AND SUICIDE MORTALITY IN PATIENTS WITH SCHIZOPHRENIA: A NATIONWIDE COHORT STUDY
Authors: Kuo *Chian-Jue , Chen Wen-Yin , Chen Pao-Huan , Tsai Shang-Ying , Chen Chiao-Chicy 
Published: February 2025

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.

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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.