Published in the Annals of Internal Medicine, systematic review data did not support routine use of haloperidol or second-generation antipsychotics (SGAs) as means of treating or preventing delirium in hospitalized adults.1,2

Investigators conducted systematic reviews of PubMed, Embase, the Cochrane Central Register of Controlled Trials, the Cumulative Index to Nursing and Allied Health Literature, and PsychINFO from inception through July 2019 for studies of antipsychotics use in patients with delirium. One review examined antipsychotics for delirium treatment; the other assessed antipsychotics for prevention. For each review, extracted outcomes included delirium incidence or duration, delirium severity, length of hospital stay, cognitive functioning, and patient mortality. Strength of evidence (SOE) was assessed for each outcome, graded as insufficient, low, moderate, or high.

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Sixteen randomized controlled trials and 10 observational studies were included in the review of antipsychotics as delirium treatment.1 Overall, no difference in sedation status (low and moderate SOE), delirium duration, length of hospital stay (moderate SOE), or mortality was observed between haloperidol and SGAs vs placebo. Compared with SGAs, haloperidol had little effect on delirium severity (moderate SOE) and cognitive functioning (low SOE). Insufficient evidence was available for comparisons of antipsychotics vs placebo or for comparisons of different SGAs.

A total of 14 randomized controlled trials were used in the review of antipsychotics for delirium prevention.2 Per these studies, no differences in delirium incidence or duration, hospital length of stay (high SOE), or mortality were observed between haloperidol and placebo when used as preventive measures. Little to no evidence was available for the effect of haloperidol on cognitive function (low SOE), inappropriate continuation, delirium severity (insufficient SOE), and sedation (insufficient SOE). In the postoperative setting, however, limited evidence suggested that SGAs may lower delirium incidence.

In both reviews, little evidence was available on the potential for antipsychotics to cause harmful neurologic effects. However, in some trials, certain cardiac effects were observed with higher frequencies among patients receiving antipsychotics. Specifically, arrhythmias and prolonged corrected QT intervals were more common among patients receiving antipsychotics.

Given these data, investigators warned against the routine use of antipsychotics for the treatment and prevention of delirium. However, high between-study heterogeneity limits the strength of these conclusions. Further study with standardized outcome measures is necessary to identify appropriate means of managing delirium in hospitalized patients.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

1. Nikooie R, Neufeld KJ, Oh ES, et al. Antipsychotics for treating delirium in hospitalized adults: a systematic review [published online September 3, 2019]. Ann Intern Med. doi:10.7326/M19-1860

2. Oh ES, Needham DM, Nikooie R, et al. Antipsychotics for preventing delirium in hospitalized adults: a systematic review [published online September 3, 2019]. Ann Intern Med. doi:10.7326/M19-1859