HK data: Long-acting injectable antipsychotics safer, more effective than oral antipsychotics for schizophrenia

Long-acting injectable antipsychotics (LAIAs) for schizophrenia are associated with lower risks of disease relapse, hospitalizations, and suicide attempts vs oral antipsychotics (OAs), without an increased risk of adverse events (AEs), according to a 16-year population-based self-controlled case series (SCCS) study by the University of Hong Kong.

“Most randomized clinical trials [on the use of LAIAs] are of relatively short duration. Data from long-term observational studies are important to establish the safety and effectiveness of LAIAs as people with schizophrenia often require lifelong antipsychotic treatment,” wrote the researchers. [JAMA Netw Open 2022;5:e2224163]

The study included 70,396 schizophrenia patients identified from the Clinical Database Analysis and Reporting System of the Hong Kong Hospital Authority. Considering that SCCS studies are within-individual comparisons, only patients who received non-treatment, LAIAs alone, OAs alone, or LAIA plus OAs during the observation period (ie, before 31 December 2019) (n=23,719; mean age at diagnosis, 39.0 years; male, 51.9 percent; mean follow-up, 12.5 years) were analyzed.

“To our knowledge, this is the first study to compare the long-term risk of disease relapse, healthcare use, and AEs associated with LAIAs vs OAs in an Asian population,” noted the researchers.

During the full treatment period, LAIAs were associated with a significant 37 percent reduction in risk of hospitalizations for any cause (incidence rate ratio [IRR], 0.63; 95 percent confidence interval [CI], 0.61–0.65), a 48 percent reduction in hospitalizations for psychiatric disorders (IRR, 0.52; 95 percent CI, 0.50–0.53), a 47 percent reduction in hospitalizations for schizophrenia (IRR, 0.53; 95 percent CI, 0.51–0.55), and a 44 percent reduction in incident suicide attempts (IRR, 0.56; 95 percent CI, 0.44–0.71) vs OAs.

To minimize the possibility that a recent outcome event might be associated with subsequent treatment, further analysis was performed for a subsequent treatment period that was beyond the first 90 days of treatment. “Similarly, the risks of hospitalizations and disease relapses were still lower with LAIAs vs OAs during the subsequent treatment period, suggesting that the lower risk was maintained after excluding the first 90 days,” added the researchers.

Compared with OAs, LAIAs were associated with lower risks of hospitalizations for somatic disorders (IRR, 0.88; 95 percent CI, 0.85–0.91), hospitalizations for cardiovascular diseases (IRR, 0.88; 95 percent CI, 0.81–0.96), and extrapyramidal symptoms (IRR, 0.86; 95 percent CI, 0.82–0.91) during the full treatment period, with similar results reported during the subsequent treatment period, indicating a generally better safety profile with LAIAs vs OAs.

In subgroup analyses, LAIAs were associated with fewer disease relapses, hospitalizations and AEs among older patients [ie, age >65 years] and patients with substance use. However, a higher risk of extrapyramidal symptoms was reported during the first 90 days of LAIA treatment in older people. Notably, early LAIAs initiators had a greater reduction in outcome events vs late initiators.

“LAIAs were associated with not only fewer disease relapses and less healthcare use, but also fewer AEs,” said the researchers. “Clinicians should more broadly consider the long-term use of LAIAs for Chinese patients with schizophrenia, especially early in the course of illness.”