TOPLINE:

Oral and parenteral antipsychotics showed similar outcomes in patients with schizophrenia experiencing agitation who presented to the emergency department (ED) with violent behavior, with no significant differences in ED return rates, mortality, or adverse events.

METHODOLOGY:

• This retrospective study included data from the TriNetX United States Collaborative Network database of 626 patients with schizophrenia (mean age, 46.0 years; 29.2% women; 42.7% White individuals; 45.2% Black or African American individuals) who presented to the ED with violent behavior and received either oral or parenteral antipsychotics between 2005 and 2025.
• The patients were divided into groups receiving either first-generation antipsychotics (FGAs), including haloperidol and droperidol, or second-generation antipsychotics (SGAs), including olanzapine, ziprasidone, and risperidone.
• In the FGA group, 218 patients received oral and 218 received parenteral antipsychotics, whereas in the SGA group, 95 patients received oral and 95 received parenteral antipsychotics.
• The researchers assessed the rates of return to the ED, mortality, and adverse events within 10 days to 6 months after the initial ED visit.

TAKEAWAY:

• Rates of return to the ED did not differ significantly between oral and parenteral routes, with odds ratios of 0.961 (95% CI, 0.650-1.420) in the FGA group and 1.180 (95% CI, 0.904-1.539) in the SGA group.
• Mortality was rare, and adverse events — including the occurrence of neuroleptic malignant syndrome, dystonia, akathisia, neutropenia, and torsade de pointes — were infrequent and not significantly different between routes of administration.
• The corrected QT intervals showed minimal variation between oral and parenteral groups (431.8 vs 426.2 for FGAs and 415.8 vs 424.4 for SGAs), with no significant differences in metabolic outcomes, including A1c and lipid profiles.

IN PRACTICE:

"Oral and parenteral antipsychotics yield similar clinical outcomes in the ED setting for acutely agitated patients with schizophrenia," the authors wrote. "Future prospective studies or chart reviews may be helpful to validate and contextualize these findings," they added.

SOURCE:

The study was led by Andrea Shehaj, Penn State College of Medicine, Hershey, Pennsylvania. It was published online on August 25, 2025, in American Journal of Emergency Medicine.

LIMITATIONS:

The study was limited by potential misclassification and missing data inherent to large databases such as TriNetX and by incomplete capture of ED revisits outside the TriNetX network. Additionally, the study lacked precision in reporting rare outcomes.

DISCLOSURES:

Funding information was not provided in the study. The authors reported having no conflicts of interest.

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