OBJECTIVES: To assess the rate of hospitalizations for schizophrenia and extrapyramidal symptoms during the combination use of clozapine and long-acting injectable antipsychotics (CLO+LAIA) and during the clozapine monotherapy (CLO-mono) among people with schizophrenia.

METHODS: In this population-based study, we utilized the electronic medical records of the Clinical Data Analysis and Reporting System (CDARS) in Hong Kong to identify individuals diagnosed with schizophrenia and prescribed clozapine and LAIA during 2004-2019. Rate of hospitalizations for schizophrenia and extrapyramidal symptoms during the full treatment periods of CLO+LAIA and CLO-mono were reported. The rate beyond the first 90 days of each treatment was further assessed to reduce potential indication bias and assess the outcomes during subsequent treatment periods.

RESULTS: Of the 70,396 individuals with schizophrenia (mean [SD] age, 44.2 [15.8] years; male, 47.2%), 5704 (mean [SD] age, 35.9 [12.1] years; male, 49.0%) were prescribed clozapine and 2745 (mean [SD] age, 36.5 [11.4] years; male, 49.0%) were prescribed both clozapine and LAIA during the observation period. The rate of hospitalizations for schizophrenia and extrapyramidal symptoms was 45.90 and 12.05 per 100 person-years during the CLO+LAIA treatment period, while the rate was 30.27 and 5.98 per 100 person-years during the CLO-mono treatment period, respectively. After excluding the first 90 days of each treatment period. The rate of hospitalizations for schizophrenia and extrapyramidal symptoms was 33.34 and 3.66 per 100 person-years during the CLO+LAIA treatment period, while the rate was 27.03 and 4.18 per 100 person-years during the CLO-mono treatment period, respectively.

CONCLUSIONS: The CLO+LAIA treatment appears not to reduce the risk of disease relapse and adverse events than CLO-mono treatments. However, further research is needed to make a detailed comparison between CLO+LAIA and CLO-mono treatments.