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Ann Intern Med. 2019 Sep 3. doi: 10.7326/M19-1859. [Epub ahead of print]

Antipsychotics for Preventing Delirium in Hospitalized Adults: A Systematic Review.

Author information

Johns Hopkins University School of Medicine, Baltimore, Maryland (E.S.O., D.M.N., R.N., K.A.R., K.J.N.).
Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland (L.M.W., A.Z.).



Delirium is an acute disorder marked by impairments in attention and cognition, caused by an underlying medical problem. Antipsychotics are used to prevent delirium, but their benefits and harms are unclear.


To conduct a systematic review evaluating the benefits and harms of antipsychotics for prevention of delirium in adults.

Data Sources:

PubMed, Embase, CENTRAL, CINAHL, and PsycINFO from inception through July 2019, without restrictions based on study setting, language of publication, or length of follow-up.

Study Selection:

Randomized, controlled trials (RCTs) that compared an antipsychotic with placebo or another antipsychotic, and prospective observational studies with a comparison group.

Data Extraction:

One reviewer extracted data and graded the strength of the evidence, and a second reviewer confirmed the data. Two reviewers independently assessed the risk of bias.

Data Synthesis:

A total of 14 RCTs were included. There were no differences in delirium incidence or duration, hospital length of stay (high strength of evidence [SOE]), and mortality between haloperidol and placebo used for delirium prevention. Little to no evidence was found to determine the effect of haloperidol on cognitive function, delirium severity (insufficient SOE), inappropriate continuation, and sedation (insufficient SOE). There is limited evidence that second-generation antipsychotics may lower delirium incidence in the postoperative setting. There is little evidence that short-term use of antipsychotics was associated with neurologic harms. In some of the trials, potentially harmful cardiac effects occurred more frequently with antipsychotic use.


There was significant heterogeneity in antipsychotic dosing, route of antipsychotic administration, assessment of outcomes, and adverse events. There were insufficient or no data available to draw conclusions for many of the outcomes.


Current evidence does not support routine use of haloperidol or second-generation antipsychotics for prevention of delirium. There is limited evidence that second-generation antipsychotics may lower the incidence of delirium in postoperative patients, but more research is needed. Future trials should use standardized outcome measures.

Primary Funding Source:

Agency for Healthcare Research and Quality. (PROSPERO: CRD42018109552).


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