Haloperidol, ziprasidone do not alter duration of delirium in ICU
The use of haloperidol or ziprasidone does not significantly shorten the duration of delirium in patients admitted to the intensive care unit (ICU), according to results from a phase III study.
The study randomized 566 patients who had acute respiratory failure or shock and hypoactive (89 percent) or hyperactive delirium (11 percent) in the ICU to receive placebo (n=184), haloperidol (maximum dose, 20 mg daily) (n=192) or ziprasidone (maximum dose, 40 mg daily) (n=190). [N Engl J Med 2018, doi: 10.1056/NEJMoa1808217]
Results showed that the median time without delirium or coma was not significantly different between placebo, haloperidol and ziprasidone (8.5 days vs 7.9 days vs 8.7 days; p=0.26 for overall effect across trial groups).
Likewise, no significant effect was observed on the number of days alive without delirium or coma during the 14-day intervention period with haloperidol (odds ratio [OR], 0.88; 95 percent confidence interval [CI], 0.64 to 1.21) or ziprasidone (OR, 1.04; 95 percent CI, 0.73 to 1.48) compared with placebo. Similarly, no significant between-group differences were observed for 30-day and 90-day survival, time to freedom from mechanical ventilation, time to ICU and hospital discharge, and the frequency of extrapyramidal symptoms.
“There is conflicting information from small trials, meta-analyses, and practice guidelines on the management of delirium in the ICU,” the investigators noted. “Haloperidol, a typical antipsychotic medication, is often used to treat hyperactive delirium in the ICU, and surveys suggest that the drug is also used to treat hypoactive delirium despite two small randomized trials that showed no evidence that haloperidol results in a shorter duration of delirium in the ICU than placebo. Atypical antipsychotic medications, such as olanzapine, quetiapine, risperidone, and ziprasidone, are also used for this purpose, and one placebo-controlled trial has suggested a benefit, whereas another showed no evidence of benefit.”
“In this trial, we found no evidence that the use of haloperidol [up to 20 mg daily] or ziprasidone [up to 40 mg daily] had an effect on the duration of delirium among patients with acute respiratory failure or shock in the ICU,” they concluded.
“One possible reason that may explain the study findings is that the mechanism of brain dysfunction that is considered to be targeted by antipsychotic medications — increased dopamine signaling — may not play a major role in the pathogenesis of delirium during critical illness,” the investigators postulated. “Another possible reason is that heterogeneous mechanisms may be responsible for delirium in critically ill patients.”