TOPLINE:

Use of long-acting injectable (LAI) antipsychotics for schizophrenia was associated with a 29% lower incidence of relapse and a 77% lower risk for all-cause mortality than oral antipsychotic use, a new study showed. Additionally, second-generation LAIs were linked to a significantly lower risk for disease relapse than first-generation LAIs.

METHODOLOGY:

• Researchers analyzed electronic health record data from the Clinical Database Analysis and Reporting System of the Hong Kong Hospital Authority between 1993 and 2023.
• The study included nearly 25,000 individuals with schizophrenia aged 65 years or older (mean age, 68.02 years; 57% women), 19% of whom were prescribed both LAI and oral antipsychotics.
• The primary outcome was disease relapse, defined as hospital admission for schizophrenia; secondary outcomes included all-cause mortality and adverse events such as cardiovascular hospital admission, extrapyramidal symptoms, acute liver injury, and acute kidney injury.
• Risks for outcome events were compared between LAI and oral antipsychotic treatment periods, adjusting for age, season, antipsychotic class, the COVID-19 Stringency Index, and concomitant medication use. The mean follow-up duration was 7.9 years.

TAKEAWAY:

• After adjusting for confounders, use of LAIs was associated with significantly lower risk for disease relapse (incidence rate ratio [IRR], 0.71; P < .0001) and all-cause mortality (hazard ratio [HR], 0.23; P < .0001) than use of oral antipsychotics.
• Second-generation LAIs were linked to a lower risk for disease relapse than first-generation LAIs (IRR, 0.63; P < .0001). Although first-generation LAIs were associated with a significantly reduced risk for all-cause mortality (HR, 0.14; P < .0001), second-generation LAIs were not.
• Adverse events were not significantly different, except for increased extrapyramidal symptoms with LAI antipsychotic use (IRR, 2.17; P = .0068) compared with oral antipsychotic use. However, the risk for extrapyramidal symptoms increased significantly only with the use of first-generation LAIs (IRR, 2.86; P = .004) but not with the use of second-generation LAIs.
• Initiation of LAIs within 2 years of diagnosis showed better treatment outcomes compared with delayed treatment initiation, particularly in reducing risk for disease relapse, acute liver injury, and acute kidney injury.

IN PRACTICE:

“Overall, LAI antipsychotics, especially second-generation medications, could be more broadly considered for long-term use among this population, particularly at an early stage of disease,” the investigators wrote.

The author of an accompanying editorial wrote, “These results might help advance the use of LAI antipsychotics among older individuals with schizophrenia. However, given the increased likelihood of severe adverse events in this population, multiple, large, high-quality, prospective studies among ethnically diverse populations will be needed before the widespread and standard use of LAI antipsychotics among these individuals.”

SOURCE:

This study was led by Yue Wei, PhD, Laboratory of Data Discovery for Health, Hong Kong Science Park, Hong Kong Special Administrative Region, China. The editorial was authored by Rajesh R. Tampi, Creighton School of Medicine, Omaha, Nebraska. Both were published online on September 30 in The Lancet Psychiatry.

LIMITATIONS:

This study did not account for antipsychotic dosages because of the different recording methods between LAI and oral medications in the database. Individuals with lived experience of schizophrenia were not included in the study design or conduct. Additionally, this study only included patients in the local public healthcare system, potentially missing those who sought care solely in the private sector.

DISCLOSURES:

This study was funded by the National Natural Science Foundation of China. Several investigators reported having financial or other ties with various organizations, including pharmaceutical companies. Full details were provided in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.