Delirium in the ICU: Could Antipsychotics Help?

Neither typical nor atypical antipsychotics appear to alleviate the effects of delirium compared with placebo in patients placed in the intensive care unit (ICU) for acute respiratory failure or shock, according to a new study.


These findings may help shed light on the conflicting body of evidence for the effects of antipsychotic medications on delirium in ICU patients.

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Researchers arrived at their conclusion after performing a randomized, double-blind, placebo-controlled trial of 1183 ICU patients who developed hypoactive or hyperactive delirium after experiencing acute respiratory failure or shock.


Study participants were randomly assigned to receive intravenous boluses of 20 mg haloperidol (maximum dose; n = 192), 40 mg ziprasidone (maximum dose; n = 190), or placebo (n = 184).


The Confusion Assessment Method for the ICU was used to determine the presence or absence of delirium. Accordingly, the volume and dose of trial drug or placebo was halved or doubled every 12 hours based on the presence or absence of delirium.


Ultimately, 566 (48%) patients developed delirium, with 89% and 11% of cases deemed hypoactive or hyperactive, respectively. Patients were treated with the trial drug or placebo for a median of 4 days.


With respect to the primary endpoint, patients in the haloperidol, ziprasidone, and placebo groups spent a median of 7.9, 8.7, and 8.5 days alive without delirium or coma throughout the 14-day intervention period, respectively.


These results indicated that neither haloperidol nor ziprasidone had any significant effect on the primary endpoint (odds ratios: 0.88 and 1.04, respectively) compared with placebo.


Likewise, neither haloperidol nor ziprasidone showed any significant impact on the secondary endpoints (30- and 90-day survival, time to freedom from mechanical ventilation, and time to ICU and hospital discharge) or the frequency of extrapyramidal symptoms vs placebo.


The findings from the study were presented at the European Society of Intensive Care Medicine 31st Annual Congress, which took place in Paris, France, from October 20 to 24, 2018.


—Christina Vogt



Girard TD, Exline MC, Carson SS, et al; MIND-USA Investigators. Haloperidol and ziprasidone for treatment of delirium in critical illness [Published online October 22, 2018]. N Eng J Med. doi:10.1056/NEJMoa1808217