Evolving patterns of antipsychotic use and polypharmacy for schizophrenia in Hong Kong: a 21-year longitudinal study

Background : Antipsychotics are the cornerstone of schizophrenia management, with antipsychotic polypharmacy commonly observed. This study aims to evaluate the trends of antipsychotic use and polypharmacy among individuals with schizophrenia in Hong Kong. Methods : This retrospective study used territory-wide electronic health records to identify all individuals aged ≥18 years diagnosed with schizophrenia in Hong Kong (2004-2024). Annual prevalence rates of antipsychotics and polypharmacy were calculated, with trend analysis using Joinpoint regression. Findings : The overall use of antipsychotics remained stable, with a slight decrease during the study period (average annual percentage change [AAPC] -0.40 [95% CI, -0.42 to -0.38]), though individual agents shifted substantially. There were opposing trends with a crossover from first to second-generation antipsychotics (SGA) predominance, while a less pronounced increase in SGA over the past decade. In 2024, olanzapine emerged as the most prevalent antipsychotic (20.6%), while clozapine utilisation grew but remained relatively limited (7.5%). Use of long-acting injectable antipsychotics (LAIA) declined (AAPC = -0.92 [-1.07 to -0.77]), except SGA-LAIA, which rose, primarily driven by LAIA-paliperidone and LAIA-aripiprazole. Antipsychotic polypharmacy prevalence decreased initially from 24.0% in 2004 to 22.4% in 2011, then increased to 28.0% in 2024 (AAPC = 0.74 [0.62 to 0.90]). In 2024, the most common combinations were oral aripiprazole and oral olanzapine (5.68%), oral amisulpride and oral olanzapine (4.22%), and LAIA-paliperidone and oral olanzapine (4.05%). Conclusion : Over the last two decades, overall antipsychotic use in schizophrenia remained stable in Hong Kong, though patterns shifted between agents. Antipsychotic polypharmacy became more prevalent, emphasising the need for further research on their safety and effectiveness.