Safety and Tolerability of Intravenous-Push Olanzapine

Introduction: Olanzapine is an atypical antipsychotic medication that is commonly used for acute agitation management. Intramuscular (IM) olanzapine is frequently used, but rapid de-escalation of patients may be limited due to the onset of this route. Use of IVP olanzapine may have a quicker onset but is currently not FDA approved and may carry higher risk for adverse effects. Off-label use of IVP olanzapine for acute agitation management has been documented in emergency medicine and critical care settings. Previous literature has reported low rates of adverse effects, with the most common being respiratory depression, hypotension, and bradycardia. The purpose of this study was to compare the safety and tolerability of IM versus IVP olanzapine administration.


Methods: This retrospective cohort study included critically ill adult patients admitted to an academic medical center intensive care unit (ICU) between March 2022 and October 2024 who received at least one dose of either IM or IVP olanzapine. Safety endpoints analyzed after administration included hypotension (systolic blood pressure less than 90 mmHg or a reduction of more than 30% from baseline), bradycardia (heart rate below 50 beats per minute or a decrease of more than 30% from baseline), cardiac dysrhythmias, respiratory depressive events, extrapyramidal symptoms (EPS), and intravenous site reactions, such as infiltration and phlebitis.


Results: A total of 800 olanzapine administrations were identified across 487 patients. A total of 54 (6.8%) adverse events were documented. Hypotension was the most common, occurring in 5.4% of administrations with no significant difference between IM (5.3%) and IVP (5.5%) administration routes (p = 0.875). Bradycardia (0.8% IM vs 0.8% IVP, p = 1) and EPS (0.3% IM vs 0.5% IVP, p = 1) were the next most common adverse effects observed, with no statistically significant difference between routes. Respiratory depression, cardiac dysrhythmia, and QTc prolongation were rare, each occurring in ≤5% of administrations. No episodes of torsades de pointes or intravenous site reactions were reported.


Conclusions: This study demonstrates that IVP olanzapine has low and comparable rates of adverse events to the IM route. IVP olanzapine may provide a safe and rapid-acting alternative to IM administration.