Clinical Question

Should antipsychotics be used to treat or prevent delirium in hospitalized patients?

Bottom Line

Evidence does not support the routine use of haloperidol or second-generation antipsychotics for the treatment or prevention of delirium in hospitalized patients. Although second-generation antipsychotics may reduce the incidence of delirium in the postoperative setting, more research is needed to confirm this. The use of second-generation anti-psychotics can also lead to QT prolongation, so patients receiving these medications should be closely monitored. (Level of Evidence = 1a–)

Synopsis

The investigators searched multiple databases including PubMed, Embase, and the Cochrane Central Register of Controlled Trials, as well as hand-searched reference lists of included articles, to find randomized controlled trials (RCTs) that compared antipsychotics with either placebo or each other for the prevention of delirium. Two reviewers independently selected articles for inclusion and assessed the risk of bias. Out of the 14 included RCTs (n = 4,281), nine had a low risk of bias (n = 3,407). All were conducted in the inpatient setting, seven in the intensive care unit. There was heterogeneity among the studies in patient populations, settings, antipsychotic medication dosing and administration, and assessment of outcomes. Haloperidol does not affect delirium incidence, delirium duration, mortality, or hospital length of stay. There is insufficient evidence to make conclusions on the effect of haloperidol on delirium severity or sedation. Although there is some evidence that second-generation antipsychotics can reduce delirium incidence in the postoperative setting (relative risk [RR] = 0.36; 95% CI, 0.26 to 0.50), these drugs have no effect on hospital length of stay or mortality and there is insufficient evidence to determine effect on delirium severity, delirium duration, or sedation. This review found no statistically significant differences between haloperidol or second-generation antipsychotics, compared with placebo, in rate of arrhythmias, QTc prolongation, or neurologic events.

In a similarly conducted systematic review evaluating the use of antipsychotics for the treatment of delirium in hospitalized patients, 16 RCTs and 10 observational studies (n = 5,607) were included. Haloperidol or second-generation antipsychotics, compared with placebo, did not affect delirium duration, mortality, sedation status, or hospital length of stay. Second-generation antipsychotic use did, however, result in more harmful cardiac effects, specifically QT prolongation compared with placebo (RR = 1.95; 95% CI, 1.03 to 3.71).

Study design: Systematic review

Funding source: Government

Allocation: Uncertain

Setting: Inpatient (any location)

Reference: Oh ES, Needham DM, Nikooie R, et al. Antipsychotics for preventing delirium in hospitalized adults: a systematic review. Ann Intern Med. 2019;171(7):474–484, and Nikooie R, Neufeld KJ, Oh ES, et al. Antipsychotics for treating delirium in hospitalized adults: a systematic review. Ann Intern Med. 2019;171(7):485–495.