Antipsychotics not effective for prevention, treatment of inpatient delirium

Two reviews analyzed dozens of studies on the use of haloperidol, second-generation antipsychotics, or placebo to treat or prevent delirium in hospitalized patients and found little to no evidence of benefit.


Antipsychotics are not effective for the prevention or treatment of delirium in hospitalized adults, according to two recent reviews.

One review focused on use of antipsychotics for the prevention of delirium and included 14 randomized controlled trials. The included trials that compared haloperidol with placebo showed no differences between the two in delirium incidence or duration, hospital length of stay, or mortality. There was also little to no evidence on the effect of haloperidol on cognitive function, delirium severity, inappropriate continuation, or sedation. For second-generation antipsychotics, there was limited evidence supporting lower delirium incidence in the postoperative setting. Looking at harms of antipsychotics, the review found little evidence of neurologic harms with short-term use but did find potentially harmful cardiac effects.

The review authors noted that guidelines suggest not using antipsychotics for prevention of delirium in the ICU and have found insufficient evidence to recommend them in other settings. The results of this review differ from a prior one, which found benefits of haloperidol prophylaxis in critically ill patients, possibly due to the inclusion of newer research. The current review was limited by heterogeneity in the studies, and more research may be needed in the perioperative setting and other high-risk populations, the study authors said.

The other review evaluated antipsychotics for treatment of inpatient delirium. It included 16 randomized controlled trials and 10 observational studies and found no difference in sedation status, delirium duration, hospital length of stay, or mortality with haloperidol and second-generation antipsychotics versus placebo. When haloperidol and second-generation antipsychotics were compared to each other, there was no difference in delirium severity or cognitive functioning. In direct comparisons of second-generation antipsychotics, there was no difference in mortality and insufficient or no evidence for other outcomes. On harms of antipsychotics, the results were similar to the prevention trials—no neurologic harm, but potential cardiac effects.

“Our findings are also consistent with recent clinical practice guidelines that do not recommend routine use of antipsychotics for treating delirium,” the authors said. They noted that some outcomes, such as patient distress and function, and some patient subgroups, such as older adults and palliative care patients, were not rigorously evaluated by the included studies, so more trials are needed.

Both reviews and an accompanying editorial were published by Annals of Internal Medicine on Sept. 3. The editorial agreed with the need for more research but added that the evidence is already definitive enough for action. “With regard to use of antipsychotics for broad treatment of delirium, I believe the findings presented are sufficient to stop this clinical practice,” the editorial said. “In my opinion, a patient-centered bundled approach that 1) identifies delirium early, 2) evaluates and addresses underlying causes, 3) prevents complications, and 4) promotes functional recovery is most likely to succeed. Identifying which practices belong in this bundle, and how to deliver it in a standardized, high-quality, and sustainable way, should be a major focus of the next generation of delirium treatment research.”