Over the last two decades, antipsychotic prescriptions for patients with schizophrenia shifted notably toward second-generation antipsychotics (SGAs), regardless of formulation, and antipsychotic polypharmacy became more prevalent, although overall use of antipsychotics remained stable, a 21-year longitudinal study has shown.
The retrospective study used territory-wide electronic health records to identify all adult patients with schizophrenia in Hong Kong from 2004 to 2024. A total of 76,584 patients (mean age at cohort entry, 42.8 years; female, 53.2 percent) were included. The median follow-up duration was 15.7 years. [Psychiatry Res 2026;364:117346]
Shift in drug classes, regardless of formulations
Overall use of antipsychotics remained relatively stable, with a slight decrease during the study period (average annual percentage change [AAPC], -0.40; 95 percent confidence interval [CI], -0.42 to -0.38).
There was a clear crossover from first-generation antipsychotics (FGAs) to SGAs as the predominant treatment choice, regardless of formulation.
“From 2004 to 2024, FGA use declined markedly [AAPC, -4.70; 95 percent CI, -0.53 to -0.48; p<0.001], whereas SGA use increased substantially [AAPC, 6.40; 95 percent CI, 6.29 to 6.54; p<0.001],” reported the researchers from the University of Hong Kong.
In 2024, prescription of oral antipsychotics was dominated by olanzapine (20.6 percent), quetiapine (12.4 percent), risperidone (11.8 percent), aripiprazole (11.6 percent), and amisulpride (8.07 percent).
Olanzapine became the most widely used agent since 2016, but its growth has recently slowed, possibly reflecting concerns about its cardiometabolic side effects, including weight gain and dyslipidaemia. “This suggests the importance of routine metabolic monitoring and timely consideration of alternative agents when long-term safety concerns arise,” noted the researchers.
Clozapine use increased only modestly (from 3.4 to 7.5 percent) over the past two decades and remained relatively uncommon. “This rise may be related to the development and implementation of Hospital Authority prescribing guidelines, which have likely facilitated its use in clinical practice. The upcoming revisions to these guidelines, such as less stringent blood monitoring after 2 years of treatment, may further optimize clozapine use,” explained the researchers.
Overall use of long-acting injectable antipsychotics (LAIAs) declined (AAPC, -0.92; 95 percent CI, -1.07 to -0.77). Notably, LAIA prescription patterns shifted from FGAs to SGAs, with decreasing use of fluphenazine, flupentixol, zuclopenthixol, and haloperidol, while use of SGA–LAIAs rose, primarily driven by LAIA–paliperidone and LAIA–aripiprazole.
“LAIA–paliperidone use increased rapidly following its introduction in 2020 and became the most prevalent LAIA by 2024,” added the researchers. “LAIA–aripiprazole also showed a gradual increase.”
Polypharmacy became more common
Antipsychotic polypharmacy prevalence decreased initially from 24.0 percent in 2004 to 22.4 percent in 2011, then increased to 28.0 percent in 2024 (AAPC, 0.74; 95 percent CI, 0.62–0.90).
In 2024, the most common combinations were oral aripiprazole and oral olanzapine (5.68 percent), oral amisulpride and oral olanzapine (4.22 percent), and LAIA–paliperidone and oral olanzapine (4.05 percent).
“Antipsychotic polypharmacy was common, but most of the frequently used combinations lack robust supporting evidence, emphasizing the need for further research on their safety and effectiveness,” commented the researchers.