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Early in-hospital administration of long-acting injectable (LAI) antipsychotics following a first admission for schizophrenia is linked to a significantly lower risk for hospital readmission, new research suggested.

Investigators used in-hospital LAI administration in patients (n = 56,211) admitted to the hospital for schizophrenia for the first time.

They compared readmission rates in patients who had received no LAI during their hospital stay with those who discontinued LAIs early and those who received LAIs without early discontinuation.

They found that most patients (83%) received no LAIs, 10% received LAIs with early discontinuation, and 6.5% received LAIs without early discontinuation.

After controlling for a variety of variables, investigators found that readmission rates increased in those who received LAIs with early discontinuation and decreased among their counterparts who received LAIs without early discontinuation compared with patients not receiving LAIs.

"The incidence of in-hospital use of LAIs among patients with a first admission for schizophrenia has remained low," investigators, led by Wen Chen, MS, ScD, of the Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan, wrote.

The findings of this study "have implications for improving the efficacy of LAI administration among patients with a first admission for schizophrenia," they added.

The study was published online on June 17 in JAMA Network Open.

LAIs Underutilized

Nonadherence to oral antipsychotics is a common cause of relapse, rehospitalization, and poor outcomes in patients with schizophrenia, while LAIs are associated with greater adherence.

Despite evidence supporting their use, LAIs remain "largely underutilized" in clinical practice — especially in Asian countries, the investigators noted. Reasons include clinicians' unfamiliarity with LAIs and insufficient time to explain to patients and their family members the rationale for recommending them. Few studies have investigated the administration of LAIs in first-admission patients with schizophrenia nationwide.

To estimate the prevalence of in-hospital use of LAIs in first-admission patients with schizophrenia and the occurrence of early discontinuation, the researchers used national cohorts of first-admission patients with schizophrenia established by the National Health Insurance Research Database in Taiwan from 2004 to 2017.

"Early discontinuation" has typically been defined as discontinuation before 36 weeks but was defined in this study as being detectable "at most, 2 months after discharge" in those receiving LAIs.

The researchers also sought to compare readmission risk in patients who received LAIs with, or without, early discontinuation vs those who did not receive LAIs.

The study included patients with schizophrenia as well as schizoaffective disorder (n = 56,211, mean [SD] age 38.1 [12.1] years, 52.3% men).

The researchers found 83.4% received no LAIs during admission, 10.1% received LAIs with early discontinuation, and 6.5% received LAIs without early discontinuation.

Between 2004-2008 and 2013-2017, the prevalence of patients receiving LAIs increased by 4%, from 15.3% to 19.3%.

LAI Education for Staff

Among those who received LAIs, 66.2% received a first-generation agent, while 33.8% took second-generation LAIs. The largest percentage took flupentixol (35.6%), followed by risperidone (27.8%) and haloperidol (23.4%). Investigators found no significant difference between first- and second-generation LAIs in patients with or without early discontinuation.

A Cox proportional hazards regression analysis that controlled for sex, prior antipsychotic use, age at first admission, and length of stay found that the readmission risk increased among patients receiving LAIs with early discontinuation but decreased in patients receiving LAIs without early discontinuation (adjusted hazard ratio [aHR], 1.25; 95% CI, 1.21-1.30 and aHR, 0.88; 95% CI, 0.84-0.92, respectively) compared with patients not receiving LAIs.

The prognostic validity of early discontinuation of in-hospital use of LAIs was supported by survival regression analyses, according to the authors: When in-hospital use of LAIs was not accompanied by early discontinuation, the readmission risk decreased by an aHR of 12% or an adjusted time ratio of 13% compared with that of patients not receiving LAIs. By contrast, if in-hospital use of LAIs was accompanied by early discontinuation, the readmission risk increased by an aHR of 25% and an adjusted time ratio of 22%.

The authors cited several study limitations. These include the fact that the claims database did not provide information on patients' clinical parameters. Because the study focused on inpatients, the results cannot be generalized to patients treated solely in outpatient settings.

There may also be residual confounding not adequately controlled for in the multivariable analyses. And they were unable to determine the specific cause of a patient's discontinuation (eg, adverse effects, inadequate efficacy, or nonadherence), so the results were based only on all-cause discontinuation.

Nevertheless, they believe the study's findings "indicate several challenges in promoting early prescription of LAIs for patients with schizophrenia." For example, one challenge is that approximately half of the first-admission patients were antipsychotic-free prior to admission, resulting in patients having little experience with different antipsychotics."

They propose that LAI-focused staff training "might be helpful for enhancing the in-hospital use of LAIs."

This work was supported by grants from the National Health Research Institutes, Taiwan, and the Ministry of Science and Technology, Taiwan. Chen reported no relevant financial relationships. The other authors' disclosures are listed in the original paper.

Batya Swift Yasgur, MA, LSW, is a freelance writer with a counseling practice in Teaneck, New Jersey. She is a regular contributor to numerous medical publications, including Medscape Medical News and WebMD, and is the author of several consumer-oriented health books as well as Behind the Burqa: Our Lives in Afghanistan and How We Escaped to Freedom (the memoir of two brave Afghan sisters who told her their story).