HK data: LAI antipsychotics superior to oral antipsychotics in older patients with schizophrenia

Long-acting injectable (LAI) antipsychotics are associated with lower risks of disease relapse and mortality than oral antipsychotics in older patients with schizophrenia, a population-based study in Hong Kong has shown.

The study also revealed a higher risk of extrapyramidal symptoms with first-generation LAI antipsychotics, but not second-generation LAI antipsychotics. [Lancet Psychiatry 2025;12:830-840]

Lower disease relapse, mortality risks

Older patients aged ≥65 years with schizophrenia are at high risk of treatment nonadherence due to cognitive decline and polypharmacy. Use of LAI antipsychotics in this population has not been systematically investigated.  

“To the best of our knowledge, this is the first population-based study to systematically evaluate disease relapse, all-cause mortality, and safety of LAI antipsychotics in older patients with schizophrenia,” wrote the researchers from the University of Hong Kong.

Using data from the Clinical Data Analysis and Reporting System, an electronic health record database of the Hong Kong Hospital Authority, the researchers identified 24,985 older patients (mean age, 68.02 years; female, 57.4 percent; LAI or oral antipsychotics, 18.8 percent) for analysis. Mean follow-up duration was 7.92 years.

LAI antipsychotics were associated with significantly reduced risks of hospital admission for schizophrenia (incidence rate ratio [IRR], 0.71; 95 percent confidence interval [CI], 0.64–0.78; p<0.0001) and all-cause mortality (hazard ratio [HR], 0.23; 95 percent CI, 0.12–0.44; p<0.0001) vs oral antipsychotics.

Why 2^nd generation LAI antipsychotics?

“Notably, second-generation LAI antipsychotics were associated with a lower risk of hospital admission for schizophrenia than first-generation LAI antipsychotics [IRR, 0.63; 95 percent CI, 0.51–0.77; p<0.0001],” highlighted the researchers.

“Our findings provide evidence on the safety outcomes of LAI antipsychotic use in older patients and are therefore clinically useful to both patients and clinicians when weighing risks and benefits of LAI antipsychotics in a balanced manner,” noted the researchers.

Compared with oral antipsychotics, risks of cardiovascular hospital admissions, acute liver injury, and acute kidney injury were comparable between LAI antipsychotics (p>0.05 for all). LAI antipsychotics were associated with an increased risk of extrapyramidal symptoms (IRR, 2.17; 95 percent CI, 1.24–3.80; p=0.0068). However, the association was linked to first-generation LAI antipsychotics only (IRR, 2.86; 95 percent, 1.41–5.84; p=0.0038), but not second-generation LAI antipsychotics (IRR, 1.86; 95 percent, 0.63–4.53; p=0.30).

Early use of LAI antipsychotics

Exploratory subgroup analyses showed that patients who commenced LAI antipsychotics early (ie, within 2 years of first schizophrenia diagnosis) had reduced risks of disease relapse, acute liver injury, and acute kidney injury with LAI antipsychotics.

“In contrast, these benefits were not observed among those who commenced LAI antipsychotics later [ie, >2 years after first schizophrenia diagnosis],” noted the researchers.

Summary

“Our findings, together with existing evidence, indicate that long-term use of LAI antipsychotics is more effective than oral antipsychotics in older patients with schizophrenia,” concluded the researchers. “Long-term use of LAI antipsychotics, particularly second-generation LAI antipsychotics, could be more broadly considered in older patients with schizophrenia after evaluating potential risks and benefits, especially in the early stages of illness.”