Long-acting injectable antipsychotics (LAIAs) reduce healthcare burden in patients with bipolar disorder without increasing risks of cardiovascular (CV) hospitalization, a population-based study in Hong Kong has shown.
“Over the past two decades, antipsychotics have been increasingly prescribed for patients with bipolar disorder,” wrote the researchers. “However, medication nonadherence remains a critical challenge, affecting approximately 60 percent of this population.” LAIAs with dosing intervals ranging from 2 weeks to 6 months can improve adherence, but their optimal use in bipolar disorder needs to be further explored. [Am J Psychiatry 2026;doi:10.1176/appi.ajp.20250793]
Researchers from the University of Hong Kong (HKU) therefore conducted a population-based, self-controlled case series study using data from the Clinical Data Analysis and Reporting System. A total of 17,841 patients with bipolar disorder (mean age, 39.7 years; male, 38.8 percent) were included. The observation period was divided into four categories: nontreatment, oral antipsychotics (OAs) alone, LAIAs alone, and concurrent use of OAs and LAIAs. The mean follow-up duration was 11.6 years.
Reduced healthcare burden with LAIAs
LAIAs were associated with significantly lower risks of all-cause emergency department visits (adjusted incidence rate ratio [aIRR], 0.85; 95 percent confidence interval [CI], 0.81–0.89), all-cause hospitalizations (aIRR, 0.79; 95 percent CI, 0.73–0.85), and psychiatric hospitalizations (aIRR, 0.67; 95 percent CI, 0.61–0.74) vs OAs.
“LAIAs were particularly effective in reducing hospitalizations for manic episodes [aIRR,0.51; 95 percent CI, 0.44–0.59] and mixed episodes [aIRR, 0.31; 95 percent CI, 0.14–0.66] vs OAs, whereas their impact on reducing hospitalization for depressive episodes was generally limited [aIRR,1.34; 95 percent CI, 0.94–1.93],” commented the researchers.
No increased risks of CV hospitalization and post–90-day EPS
Antipsychotics are known to increase CV mortality through both direct effects (eg, arrhythmias and QTc prolongation) and indirect risks (eg, obesity). They also increase risks of movement disorders, particularly extrapyramidal symptoms (EPS).
“[In this study,] LAIAs were not associated with an increased risk of nonpsychiatric hospitalizations [aIRR, 0.97; 95 percent CI, 0.87–1.08], notably those for CV diseases [aIRR, 0.84; 95 percent CI, 0.62–1.14], vs OAs,” highlighted the researchers.
Although LAIAs were initially associated with an increased risk of EPS (aIRR, 2.95; 95 percent CI,1.40–6.22), this difference became statistically nonsignificant after the first 90 days of treatment were excluded.
“Considering the potential benefits of the use of LAIAs, we need to further explore the barriers to uptake, and be mindful of the small risk of EPS,” commented Professor Esther Wai-Yin Chan of the Department of Pharmacology and Pharmacy, HKU.
A closer look at each LAIA
To provide further insight, the researchers evaluated seven LAIAs available in Hong Kong’s public hospitals individually and collectively.
Second-generation LAIAs, including aripiprazole, paliperidone, and risperidone, were associated with lower risks of all-cause and psychiatric hospitalizations than their oral formulations, whereas this difference was not observed for first-generation LAIAs, such as flupenthixol and haloperidol.
Notably, aripiprazole was the only LAIA associated with a reduced risk of hospitalizations for depressive episodes (aIRR, 0.20; 95 percent CI=0.04–0.95) vs its oral counterpart.