The Impact of Clozapine Delay on Clinical Outcomes in Schizophrenia

Background: Clozapine is the drug of choice indicated for treatment-resistant schizophrenia (TRS), but delays in initiation and underutilization might have affected its effectiveness in practice. In this study, we sought to examine the clinical outcomes of patients on clozapine treatment and if a delay in initiation was associated with poorer outcomes.Methods: This study was conducted at a tertiary mental health institution in patients aged 21 to 80 years from January 2016 to October 2019 who were on a stable dose of clozapine for 2 weeks. All patients were assessed using the Structured Clinical Interview for DSM-IV-TR (SCID-I) to ascertain diagnoses of schizophrenia and schizoaffective disorder. Each patient was assessed on the Positive and Negative Syndrome Scale (PANSS) and Social Occupational Functioning Assessment Scale (SOFAS). Past antipsychotic treatment trials were obtained from the medical records. Symptom remission status was defined using the PANSS symptom criteria proposed by Andreasen and colleagues in 2005. Functional remission was defined as a SOFAS score ≥ 60.Results: A total of 159 individuals with schizophrenia or schizoaffective disorder were recruited. The mean age of patients was 40.01 years, and the majority of patients were male (64.2%) and Chinese (85.5%). Thirty-seven patients (23.3%) achieved symptom remission, and 101 (63.5%) achieved functional remission. The median number of antipsychotic trials before clozapine initiation was 6 (interquartile range, 5-8). Patients in either symptom or functional remission had shorter time periods and fewer numbers of antipsychotic trials before first clozapine initiation. However, the trend was statistically significant only for median number of antipsychotic trials in the functional remission (P = .027) and symptom remission (P = .011) groups.Conclusion: Our study found a significant delay in the initiation of clozapine despite current guidelines indicating it for TRS. This delay might have contributed to the poorer clinical outcomes. Further research is needed to provide a clearer understanding of clozapine delay, evaluate its impact on outcomes, and find ways to improve access to clozapine.