Clinical Utility and Safety of Slower-than-Recommended Titration of Clozapine for Treatment-Resistant Schizophrenia: a Retrospective Cohort Study

Slow titration of clozapine is recommended given the risk of serious adverse effects. However, the utility and safety of slower-than-recommended titration of clozapine remain unclear. Consequently, we aimed to investigate the clinical utility and safety of slower-than-recommended titration of clozapine for treatment-resistant schizophrenia. We conducted a retrospective chart review of 152 inpatients with treatment-resistant schizophrenia who had been newly started on clozapine in a tertiary psychiatric public hospital between April 2012 and March 2018. The primary outcome was clozapine continuation for the first 18 weeks. We performed multivariate logistic regression to identify the association between the rate of clozapine dose titration and clozapine continuation for the first 18 weeks. Among the 152 inpatients, 122 (80%) could continue clozapine for the first 18 weeks. There was no significant association between the rate of clozapine dose titration and clozapine continuation for the first 18 weeks (adjusted odds ratio 1.23; 95% CI 0.29-5.26;p = 0.78). Our findings indicate that slower-than-recommended titration of clozapine may not improve toward clozapine continuation for the first 18 weeks. Therefore, it may not be a beneficial option in terms of safe clozapine continuation when starting clozapine for treatment-resistant schizophrenia.