Association of Antipsychotic Dose with Surrogate Efficacy and Safety Outcomes in Hospitalized Older Adults: A Retrospective Cohort Study.

Abstract

Introduction: Antipsychotics are frequently used in hospitalized older adults to manage agitation and delirium, despite limited supporting evidence and known risks. While guidelines recommend low doses and short durations, high doses remain common. This study evaluated the efficacy and safety of low-versus high-dose antipsychotics in hospitalized adults aged ≥ 65 years.

Methods: This retrospective cohort study included patients from two hospitals within a single health system between August 2021 and August 2023. Patients were included if they received inpatient administration of haloperidol, olanzapine, quetiapine, risperidone, or ziprasidone and excluded for prior antipsychotic use, benzodiazepine use, psychiatric comorbidities, or prolonged intensive care unit (ICU) admission. Patients were stratified into low- and high-dose groups. Low doses were haloperidol 0.5-1 mg, olanzapine 2.5-5 mg, quetiapine 12.5-25 mg, risperidone 0.25-1 mg, or ziprasidone 10-20 mg, and doses were considered high if they were above the criteria for a low dose. The primary outcome was a surrogate marker of efficacy: antipsychotic redosing within 6 h. Secondary outcomes included length of stay (LOS), antipsychotic continuation at discharge, and possible antipsychotic-associated adverse events through 90 days post discharge as assessed through index and readmission records. Multivariable logistic regression was used to assess factors associated with antipsychotic redosing within 6 h.

Results: A total of 305 patients were included (low dose: n = 176; high dose: n = 129). Redosing within 6 h occurred at similar rates in low versus high groups (n = 25 [14.2%] versus n = 18 [14.0%], p = 0.950). Multivariable regression showed haloperidol use (compared with quetiapine) was associated with higher odds of redosing. Adverse event rates were numerically higher in the high-dose group, including a greater incidence of inpatient pneumonia and mortality, though most deaths occurred in patients receiving palliative care.

Conclusions: Low- and high-dose antipsychotics demonstrated similar short-term efficacy, but higher doses may carry increased risk of adverse events in hospitalized older adults. Clinicians should prioritize low-dose regimens and evaluate the necessity of antipsychotic use in this vulnerable population.