Esther S. Oh, MD, PhD; Dale M. Needham, MD, PhD; Roozbeh Nikooie, MD; Lisa M. Wilson, ScM; Allen Zhang, BS; Karen A. Robinson, PhD *; Karin J. Neufeld, MD, MPH *
Disclaimer: The project was funded under contract HHSA290201500006I/HHSA29032008T from the AHRQ, U.S. Department of Health and Human Services (HHS). The authors of this manuscript are responsible for its content. Statements in the manuscript do not necessarily reflect the official views of or imply endorsement by AHRQ or HHS.
Acknowledgment: The authors thank Carrie Price, MLS, for peer reviewing our literature search. They also acknowledge contributions made by Sumana Vasishta, MBBS; Mounica Koneru, MBBS; Jeanette Edelstein, MA; Sriharsha Singu, MBBS; Amulya Balagani, MBBS; Louay H. Aldabain, MD, Narjes Akhlaghi, MD; Mary Zulty, DO; Sanjay Singh, MD; and Matthew Picchiello, BA.
Financial Support: By the AHRQ (contract 290-2015-00006I-2).
Disclosures: Dr. Needham reports a contract from the AHRQ during the conduct of the study. Dr. Nikooie reports a contract from the AHRQ during the conduct of the study. Dr. Neufeld reports a contract from AHRQ during the conduct of the study and personal fees from Merck and grants from Hitachi outside the submitted work. Ms. Wilson reports contract HHSA290201500006I/HHSA29032008T from AHRQ during the conduct of the study. Mr. Zhang reports a contract from the AHRQ during the conduct of the study. Dr. Robinson reports a contract from AHRQ during the conduct of the study. Dr. Neufeld reports a contract from AHRQ during the conduct of the study and personal fees from Merck and grants from Hitachi outside the submitted work. Drs. Neufeld and Needham were panel members for the Society of Critical Care Medicine Clinical Practice Guidelines for the Prevention and Management of Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Disruption in Adult Patients in the ICU and the American Geriatrics Society Clinical Practice Guideline for Postoperative Delirium in Older Adults. The first author and none of the other authors have any affiliations or financial involvement that conflict with the material presented in this report. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M19-1859.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that her spouse has stock options/holdings with Targeted Diagnostics and Therapeutics. Darren B. Taichman, MD, PhD, Executive Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Catharine B. Stack, PhD, MS, Deputy Editor, Statistics, reports that she has stock holdings in Pfizer, Johnson & Johnson, and Colgate-Palmolive. Christina C. Wee, MD, MPH, Deputy Editor, reports employment with Beth Israel Deaconess Medical Center. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Yu-Xiao Yang, MD, MSCE, Deputy Editor, reports that he has no financial relationships or interest to disclose.
Reproducible Research Statement:Study protocol: Available at www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42018109552. Statistical code and data set: Available from Ms. Wilson (e-mail, LisaWilson@jhmi.edu); abstracted data for full review are published on the Systematic Review Data Repository (https://srdr.ahrq.gov/).
Corresponding Author: Karin J. Neufeld, MD, MPH, Department of Psychiatry, Johns Hopkins Bayview Medical Center, A4 Center Suite 457, 4940 Eastern Avenue, Baltimore, MD 21224. e-mail, email@example.com.
Current Author Addresses: Dr. Oh: Division of Geriatric Medicine and Gerontology, Johns Hopkins University School of Medicine, Mason F. Lord Building Center Tower, 5200 Eastern Avenue, Seventh Floor, Baltimore, MD 21224.
Dr. Robinson: Department of Medicine, Johns Hopkins University School of Medicine, 1830 East Monument Street, Room 8068, Baltimore, MD 21287.
Drs. Needham and Nikooie: Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, 1830 East Monument Street, Fifth Floor, Baltimore, MD 21287.
Ms. Wilson and Mr. Zhang: Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, 624 North Broadway, Sixth Floor, Baltimore, MD 21205.
Dr. Neufeld: Department of Psychiatry, Johns Hopkins Bayview Medical Center, A4 Center Suite 457, 4940 Eastern Avenue, Baltimore, MD 21224.
Author Contributions: Conception and design: E.S. Oh, D.M. Needham, R. Nikooie, L.M. Wilson, A. Zhang, K.A. Robinson, K.J. Neufeld.
Analysis and interpretation of the data: E.S. Oh, D.M. Needham, R. Nikooie, L.M. Wilson, A. Zhang, K.A. Robinson, K.J. Neufeld.
Drafting of the article: E.S. Oh, R. Nikooie, A. Zhang, K.A. Robinson, K.J. Neufeld.
Critical revision of the article for important intellectual content: E.S. Oh, D.M. Needham, R. Nikooie, L.M. Wilson, A. Zhang, K.A. Robinson, K.J. Neufeld.
Final approval of the article: E.S. Oh, D.M. Needham, R. Nikooie, L.M. Wilson, A. Zhang, K.A. Robinson, K.J. Neufeld.
Provision of study materials or patients: L.M. Wilson, A. Zhang.
Statistical expertise: A. Zhang.
Obtaining of funding: D.M. Needham, A. Zhang, K.A. Robinson, K.J. Neufeld.
Administrative, technical, or logistic support: D.M. Needham, L.M. Wilson, A. Zhang, K.A. Robinson, K.J. Neufeld.
Collection and assembly of data: E.S. Oh, R. Nikooie, L.M. Wilson, A. Zhang, K.A. Robinson, K.J. Neufeld.
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.
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.
Randomized, controlled trials (RCTs) that compared an antipsychotic with placebo or another antipsychotic, and prospective observational studies with a comparison group.
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.
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.
Agency for Healthcare Research and Quality. (PROSPERO: CRD42018109552)
Table. Characteristics of Included Randomized Controlled Trials
Summary of the strength of evidence and conclusions for the effect of antipsychotics on critical outcomes.
Each circle represents a study; the size of the circle corresponds to the study sample size. Shaded areas indicate specific comparisons for which we concluded there was little to no difference. Crossed-out columns indicate no evidence identified for the specific comparison. “Insufficient evidence” means we concluded that evidence was insufficient to make a conclusion, because of unknown consistency due to single trials, small sample size (imprecision), high risk of bias, or inconsistency in study results. We found no randomized controlled trials evaluating the role of antipsychotics for the critical outcome of cognitive function and inappropriate continuation of antipsychotics. Second-gen = second-generation antipsychotic.
Meta-analysis of difference in the incidence of adverse events in studies evaluating effect of antipsychotics.
RR = relative risk; QTc = corrected QT interval.
* I2 for all the meta-analysis was 0.0%.
Pooled outcome meta-analysis for delirium incidence and mortality.
RR = relative risk.
* I2 for the meta-analysis was 44%.
† I2 for the meta-analysis was 0%.
‡ Olanzapine or risperidone.
The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.
University of Medicine 1, Yangon, Myanmar
September 12, 2019
Antipsychotics for Delirium
9 September 2019To the Editor:I would like to applaud the 3 September 2019 article “Antipsychotics for Preventing Delirium in Hospitalized Adults: A Systematic Review”. As a psychiatrist teaching child and adolescent psychiatry in medical schools for the past two years in Malawi and, currently, as a Fulbright Scholar in Myanmar, I am aware how liberally 2nd generation antipsychotics are used in both countries, for both adults and children, well outside of recommended indications. My recently published article1 on Donkin Psychosis encourages not reflexively using antipsychotics to treat a version of puerperal psychosis associated with pre-eclampsia. The paper, while not reflecting well on the speed of our consultation service in the primary teaching hospital, serendipitously arrived at the above conclusion from a patient’s rapid recovery when her hypertension alone was adequately treated. 1) Puerperal Psychosis: A brief review and unusual case report Stewart, GH, Gadama, LA, Kerry, V Malawi Med J. 2019 Mar; 31(161): https://dx.doi.org/10.4314/mmj.v31i2.11Thank you,George H. Stewart, MDFulbright ScholarHonorary ProfessorUniversity of Medicine 1, Yangon, Myanmargeorgehstewart000@gmail.com
Oh ES, Needham DM, Nikooie R, et al. Antipsychotics for Preventing Delirium in Hospitalized Adults: A Systematic Review. Ann Intern Med. [Epub ahead of print 3 September 2019]:. doi: 10.7326/M19-1859
Download citation file:
Published: Ann Intern Med. 2019.
Results provided by:
Copyright © 2019 American College of Physicians. All Rights Reserved.
Print ISSN: 0003-4819 | Online ISSN: 1539-3704
Conditions of Use