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Antipsychotics for the Prevention and Treatment of Delirium

Comparative Effectiveness Review, No. 219

Investigators: , M.D., M.P.H., , M.D., Ph.D., , M.D., Ph.D., , Sc.M., , M.D., , B.S., , M.B.B.S., , M.B.B.S., , M.B.B.S., , M.D., and , Ph.D.

Author Information
Rockville (MD): Agency for Healthcare Research and Quality (US); .
Report No.: 19-EHC019-EF

Structured Abstract

Objectives:

To assess benefits and harms of antipsychotics for the prevention and treatment of delirium in adult patient populations.

Data sources:

We searched PubMed®, Embase®, the Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL®), and PsycINFO® through March 2019. We also hand-searched the reference lists of included articles, relevant reviews, and delirium-specific bibliographic repositories.

Review methods:

We included randomized controlled trials (RCTs) of antipsychotics that evaluated benefits or harms, and also observational studies that reported harms. Two reviewers independently screened search results for eligibility, serially abstracted data, and independently assessed the risk of bias of the studies and graded the strength of evidence (SOE) for prespecified critical outcomes: delirium severity, cognitive functioning, length of stay in hospital, inappropriate continuation of antipsychotic drugs, falls, sedation, and caregiver burden/strain.

Results:

We identified 14 RCTs and 1 observational study evaluating the use of antipsychotics in prevention of delirium. For the treatment of delirium, we identified 19 RCTs and 25 observational studies. Two RCTs were classified as both a prevention and treatment trial. In trials of the prevention of delirium across all populations, there was no difference in delirium incidence for haloperidol versus placebo (relative risk [RR], 0.94; 95% confidence interval [CI], 0.77 to 1.16). Second-generation antipsychotics, compared with placebo, may decrease delirium incidence in postoperative patients at risk for delirium (RR, 0.36; 95% CI, 0.26 to 0.50). Antipsychotics (both haloperidol and second-generation), compared to placebo, demonstrated no differences for length of stay in hospital (low SOE for second-generation antipsychotics and high SOE for haloperidol). We were unable to draw conclusions regarding the effect of antipsychotics on sedation, falls, and delirium severity (insufficient SOE). We found no studies evaluating cognitive functioning, inappropriate continuation of antipsychotic drugs, or caregiver burden/strain. For treatment of delirium, there was little to no difference in effect of haloperidol and second-generation antipsychotics compared with placebo for length of stay in hospital (moderate SOE) and sedation (low and moderate SOE, respectively) with insufficient or no evidence for cognitive functioning or delirium severity. Also, effects of second-generation antipsychotics were not significantly different compared with haloperidol for delirium severity (moderate SOE), cognitive functioning (low SOE), length of stay in hospital (moderate SOE), and sedation (moderate SOE). We found no studies reporting inappropriate continuation of antipsychotic drugs, falls, or caregiver burden/strain. We did not find statistically significant differences for haloperidol or second-generation antipsychotics in neurological harms, including extrapyramidal side effects and neuroleptic malignant syndrome. However, cardiac harms tended to occur more frequently with antipsychotics, specifically prolongation of QT interval with second-generation antipsychotics.

Conclusions:

Haloperidol or second-generation antipsychotics, compared to placebo, used for the prevention or treatment of delirium did not improve length of stay in hospital. We found little or no evidence to determine the effect of antipsychotics on cognitive function, delirium severity, or caregiver burden. Second-generation antipsychotics may decrease delirium incidence in postoperative patients, but this evidence is limited and requires more study. We did not detect neurological harms associated with haloperidol or second-generation antipsychotics used for the prevention or treatment of delirium. However, cardiac effects tended to occur more frequently in those receiving antipsychotics. Future studies should include standardized, clinically meaningful measures of patient distress, subsequent memories of delirium, caregiver burden and distress, inappropriate continuation of antipsychotic therapy, and long-term cognitive and functional outcomes.

Contents

Prepared for: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services, 5600 Fishers Lane, Rockville, MD 20857; www.ahrq.gov Contract No. 290-2015-00006-I, 290-32008-T Prepared by: Johns Hopkins University Evidence-based Practice Center, Baltimore, MD

Suggested citation:

Neufeld KJ, Needham DM, Oh ES, Wilson LM, Nikooie R, Zhang A, Koneru M, Balagani A, Singu S, Aldabain L, Robinson KA. Antipsychotics for the Prevention and Treatment of Delirium. Comparative Effectiveness Review No. 219. (Prepared by the Johns Hopkins University Evidence-based Practice Center under Contract No. 290-2015-00006-I-2.) AHRQ Publication No. 19-EHC019-EF. Rockville, MD: Agency for Healthcare Research and Quality; September 2019. Posted final reports are located on the Effective Health Care Program search page. DOI: https://doi.org/10.23970/AHRQEPCCER219.

This report is based on research conducted by the Johns Hopkins University Evidence-based Practice Center (EPC) under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290-2015-00006-I-2). The findings and conclusions in this document are those of the authors, who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ. Therefore, no statement in this report should be construed as an official position of AHRQ or of the U.S. Department of Health and Human Services.

Two investigators were members of the guideline panel for a 2018 Society for Clinical Care Medicine guideline for the management of pain, sedation, delirium, rehabilitation, and sleep for critically ill patients. Two investigators co-authored the American Geriatric Society guidelines for post-operative delirium in older adults. None of the other investigators have any affiliations or financial involvement that conflicts with the material presented in this report.

The information in this report is intended to help healthcare decision makers—patients and clinicians, health system leaders, and policymakers, among others—make well-informed decisions and thereby improve the quality of healthcare services. This report is not intended to be a substitute for the application of clinical judgment. Anyone who makes decisions concerning the provision of clinical care should consider this report in the same way as any medical reference and in conjunction with all other pertinent information, i.e., in the context of available resources and circumstances presented by individual patients.

This report is made available to the public under the terms of a licensing agreement between the author and the Agency for Healthcare Research and Quality. This report may be used and reprinted without permission except those copyrighted materials that are clearly noted in the report. Further reproduction of those copyrighted materials is prohibited without the express permission of copyright holders.

AHRQ or U.S. Department of Health and Human Services endorsement of any derivative products that may be developed from this report, such as clinical practice guidelines, other quality enhancement tools, or reimbursement or coverage policies, may not be stated or implied.

This report may periodically be assessed for the currency of conclusions. If an assessment is done, the resulting surveillance report describing the methodology and findings will be found on the Effective Health Care Program website at www.effectivehealthcare.ahrq.gov. Search on the title of the report.

People using assistive technology may not be able to fully access information in this report. For assistance contact vog.shh.qrha@CPE.

Bookshelf ID: NBK546180PMID: 31509366

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