Abstract

Clozapine treatment remains the gold standard for treatment-resistant schizophrenia. This study aimed to describe temporal trends in clozapine use at discharge among patients with schizophrenia at two of the largest public psychiatric hospitals in Taiwan over a twelve-year period. Patients with schizophrenia discharged from the two study hospitals between 2006 and 2017 (n = 24,101) were included in the analysis. Antipsychotic augmentation was defined as concomitant use of a second antipsychotic as augmentation to clozapine treatment. Changes in the rate of clozapine use and antipsychotic augmentation at discharge over time were analyzed using the Cochran-Armitage trend test. Patients discharged on clozapine had significantly longer hospital stays than other patients. The rate of clozapine use at discharge increased from 13.8% to 20.0% over time (Z = 6.88, p < .0001). Concomitant use of anticholinergic medication was more common in patients receiving antipsychotic augmentation than clozapine antipsychotic monotherapy. Among patients discharged on clozapine, the rate of augmentation with a second antipsychotic increased from 19.1% to 36.2% over time (Z = 6.58, p < .0001). Among patients receiving antipsychotic augmentation, use of another second-generation antipsychotic as the augmentation agent grew from 32.6% to 65.5% over time (Z = 8.90, p < .0001). The increase in clozapine use was accompanied by an increase in concomitant use of a second antipsychotic as augmentation during the study period. Further studies are warranted to clarify the risk/benefit of this augmentation strategy. Clozapine may still be underutilized, and educational programs are needed to promote clinical use of clozapine.

Highlights

  • Many agree clozapine is by far the most effective treatment for T­ RS6–8

  • Not all patients with TRS will respond to clozapine antipsychotic monotherapy

  • It is estimated that approximately 40–70% of patients with TRS do not respond to clozapine antipsychotic monotherapy of adequate dose and ­duration[22,23]

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Summary

Introduction

Many agree clozapine is by far the most effective treatment for T­ RS6–8. Clozapine is often underused in patients with TRS despite its proven efficacy. Potential adverse effects, such as metabolic syndrome, bowel obstruction, agranulocytosis, pneumonia, and myocarditis may have limited its u­ se[13,14,15]. In the event of clozapine antipsychotic monotherapy failure, rates of augmentation with a second antipsychotic agent fluctuate from 18 to 44%26,27. The aim of this study was to illustrate the temporal trends in clozapine use and augmentation with a second antipsychotic to clozapine treatment at time of discharge among patients with schizophrenia discharged from two public psychiatric hospitals in Taiwan over a twelve-year period (2006–2017)

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