Quetiapine and Olanzapine for the Treatment of Hyperactive ICU Delirium in Adults

Introduction: Current Society of Critical Care Medicine (SCCM) guidance acknowledges the use of antipsychotic agents in current clinical practice around hyperactive ICU delirium but does not corroborate their use with strong evidence in favor; existing guidance is limited beyond what is extrapolated from safety profiles of antipsychotics in non-ICU delirium indications. The purpose of this retrospective analysis is to compare the safety and effectiveness of quetiapine and olanzapine in the treatment of hyperactive ICU delirium across all surgical intensive care units (SICUs) in NYU Langone Health system (NYU-LH).


Methods: This is a multicenter, retrospective chart review of adult medical records for patients who experienced hyperactive delirium in any SICU in NYU-LH who failed non-pharmacological treatment and received either quetiapine or olanzapine as second-line therapy. The study examines the safety and efficacy of each antipsychotic, with the primary outcome being delirium and coma-free days.


Results: 860 patients were screened for study inclusion from January 1st, 2023-April 30th, 2025, 101 patients who received quetiapine and 18 patients who received olanzapine were included. Demographic data such as baseline use of psychiatric medications and mechanical ventilation were similar between groups excepting morphine milligram equivalents prior to the start of the antipsychotic standing order (145 [IQR 13.75, 1053.75] vs 36.25 [IQR 0, 175], p = 0.027). The olanzapine group had more delirium-free days in the ICU (4.77 [IQR 1.13, 15.34] vs 11.78 [IQR 2.62, 33.66], p = 0.044), more delirium and coma-free days (8 [IQR 0, 12] vs 11 [IQR 6.75, 13], p = 0.037) and a greater percentage of delirium-free days out of the total ICU length of stay (50.92 [IQR 9.78, 86.25] vs 79.23 [IQR 31.64, 90.17], p = 0.041).


Conclusions: Olanzapine use was associated with more delirium-free days in the ICU, a higher percentage of delirium-free days out of the total ICU length of stay, and more delirium and coma-free days in comparison to quetiapine use. Safety profiles were similar between groups. These results suggest that olanzapine is the optimal choice of antipsychotic for the treatment of hyperactive ICU delirium in adults.