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Antipsychotic medication for prevention and treatment of delirium in hospitalized adults: a systematic review and meta-analysis
Open accessAbstract
Objectives: To evaluate the effectiveness of antipsychotic medications in preventing and treating delirium. Design: Systematic review and meta‐analysis. Setting: PubMed, EMBASE , CINAHL , and ClinicalTrials.gov databases were searched from January 1, 1988, to November 26, 2013. Participants: Adult surgical and medical inpatients. Intervention: Antipsychotic administration for delirium prevention or treatment in randomized controlled trials or cohort studies. Measurements: Two authors independently reviewed all citations, extracted relevant data, and assessed studies for potential bias. Heterogeneity was considered as chi‐square P < .1 or I 2 > 50%. Using a random‐effects model (I 2 > 50%) or a fixed‐effects model (I 2 < 50%), odds ratios ( OR s) were calculated for dichotomous outcomes (delirium incidence and mortality), and mean or standardized mean difference for continuous outcomes (delirium duration, severity, hospital and intensive care unit ( ICU ) length of stay ( LOS )). Sensitivity analyses included postoperative prevention studies only, exclusion of studies with high risk of bias, and typical versus atypical antipsychotics. Results: Screening of 10,877 eligible records identified 19 studies. In seven studies comparing antipsychotics with placebo or no treatment for delirium prevention after surgery, there was no significant effect on delirium incidence ( OR = 0.56, 95% confidence interval ( CI ) = 0.23–1.34, I 2 = 93%). Using data reported from all 19 studies, antipsychotic use was not associated with change in delirium duration, severity, or hospital or ICU LOS , with high heterogeneity among studies. No association with mortality was detected ( OR = 0.90, 95% CI = 0.62–1.29, I 2 = 0%). Conclusion: Current evidence does not support the use of antipsychotics for prevention or treatment of delirium. Additional methodologically rigorous studies using standardized outcome measures are needed.
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In the citing paper
“In the UK however, detection rates have increased over the past 10 years.281”
From Dementia prevention, intervention, and care: 2020 report of the Lancet Commission (2020) · cites this paper as [281]
Experimental — accuracy not yet measuredIn the citing paper
“While antipsychotics such as risperidone, haloperidol, ziprasidone and olanzapine are sometimes used to manage agitation or psychotic symptoms in delirium, there is a lack of strong evidence to support their use 194 .”
From Mental health care for older adults: recent advances and new directions in clinical practice and research (2022) · cites this paper as [194]
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“The current results were consistent with the findings of a meta-analysis(34) that included three RCTs of haloperidol versus placebo.(18,19,23) No association between antipsychotics and prevention of postoperative delirium was demonstrated.”
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Postoperative Delirium in Older Adults: Best Practice Statement from the American Geriatrics Society
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Self-citationOlanzapine vs haloperidol: treating delirium in a critical care setting
Skrobik, Y. K., Bergeron, N., Dumont, M., & Gottfried, S. B. (2003) · Intensive Care Medicine · doi:10.1007/s00134-003-2117-0 · Cited by 455
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“68, I(2) = 77%).(13,14,17,18) Severity of delirium was not associated with administration of antipsychotics in 464 participants in eight studies (SMD = 0.”
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BackgroundDorman, T. (2011) · Yearbook of Critical Care Medicine · doi:10.1016/s0734-3299(10)79437-5 · Cited by 385
Haloperidol prophylaxis decreases delirium incidence in elderly patients after noncardiac surgery
Wang, W., Li, H.-L., Wang, D., Zhu, X. D., Li, S., Yao, G., Chen, K.-S., Gu, X.-E., & Zhu, S. (2011) · Critical Care Medicine · doi:10.1097/ccm.0b013e3182376e4f · Cited by 308 · cited 2×
“The current results were consistent with the findings of a meta-analysis(34) that included three RCTs of haloperidol versus placebo.(18,19,23) No association between antipsychotics and prevention of postoperative delirium was demonstrated.”
ResultEfficacy of Risperidone for Prevention of Postoperative Delirium in Cardiac Surgery
Prakanrattana, U., & Prapaitrakool, S. (2007) · Anaesthesia and Intensive Care · doi:10.1177/0310057x0703500509 · Cited by 280 · cited 1×
“65 days, I(2) = 0%).(13,14,17,18,21) There was no significant association with ICU LOS in 1,400 participants from seven studies (MD = 0.”
BackgroundA Double-Blind Trial of Risperidone and Haloperidol for the Treatment of Delirium
Han, C.-S., & Kim, Y. (2004) · Psychosomatics · doi:10.1016/s0033-3182(04)70170-x · Cited by 268
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“68, I(2) = 77%).(13,14,17,18) Severity of delirium was not associated with administration of antipsychotics in 464 participants in eight studies (SMD = 0.”
BackgroundA randomized controlled trial of quetiapine versus placebo in the treatment of delirium
Tahir, T. A., Eeles, E. M., Karapareddy, V., Muthuvelu, P., Chapple, S., Phillips, B., Adyemo, T., Farewell, D. M., & Bisson, J. I. (2010) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2010.05.006 · Cited by 158 · cited 1×
“There were 12 treatment studies that included mixed surgical and nonsurgical populations, with average ages ranging from 39(24) to 84.(29) Five studies focused on an ICU population.”
BackgroundRecovery Room Delirium Predicts Postoperative Delirium After Hip-Fracture Repair
Sharma, P. T., Sieber, F. E., Zakriya, K. J., Pauldine, R. W., Gerold, K. B., Hang, J., & Smith, T. H. (2005) · Anesthesia & Analgesia · doi:10.1213/01.ane.0000167383.44984.e5 · Cited by 142 · cited 1×
“This design, which selected a subset of individuals at highest risk of developing delirium on subsequent hospital days, may not be comparable with other designs that treat all people regardless of risk.(40,41) Notwithstanding this criticism, the current findings are important to report given that they are consistent w…”
ResultOutcomes of Early Delirium Diagnosis After General Anesthesia in the Elderly
Neufeld, K. J., Leoutsakos, J., Sieber, F. E., Wanamaker, B. L., Chambers, J. J. G., Rao, V., Schretlen, D. J., & Needham, D. M. (2013) · Anesthesia & Analgesia · doi:10.1213/ane.0b013e3182973650 · Cited by 138 · cited 1×
“This design, which selected a subset of individuals at highest risk of developing delirium on subsequent hospital days, may not be comparable with other designs that treat all people regardless of risk.(40,41) Notwithstanding this criticism, the current findings are important to report given that they are consistent w…”
ResultSelf-citationHaloperidol prophylaxis in critically ill patients with a high risk for delirium
van den Boogaard, M., Schoonhoven, L., van Achterberg, T., van der Hoeven, J. G., & Pickkers, P. (2013) · Critical Care · doi:10.1186/cc11933 · Cited by 133
Consequences of Preventing Delirium in Hospitalized Older Adults on Nursing Home Costs
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Self-citationComparative efficacy study of haloperidol, olanzapine and risperidone in delirium
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Risperidone versus olanzapine for the treatment of delirium
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Larsen, K. A., Kelly, S., Stern, T. A., Bode, R. H., Price, L. L., Hunter, D. J., Gulczynski, D., Bierbaum, B. E., Sweeney, G. A., Hoikala, K. A., et al. (2010) · Psychosomatics · doi:10.1176/appi.psy.51.5.409 · Cited by 74
Friedman, J. I., Soleimani, L., McGonigle, D. P., Egol, C., & Silverstein, J. H. (2013) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2013.13040458 · Cited by 65 · cited 2×
“The only systematic review to include all of the same studies identified in this review did not perform a meta-analysis.(33) An additional five meta-analyses included up to six of the same studies analyzed in this report and concluded that there was a modest postoperative delirium protective effect of antipsychotics.”
ResultDo antipsychotics prevent postoperative delirium? A systematic review and meta‐analysis
Fok, M. C., Sepehry, A. A., Frisch, L., Sztramko, R., van der Burg, B. L. S. B., Vochteloo, A. J. H., & Chan, P. (2015) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.4240 · Cited by 64 · cited 1×
“Results for this study required imputation because of a lost randomization code.(39) The only systematic review to include all of the same studies identified in this review did not perform a meta-analysis.”
MethodDelirium Diagnosis Methodology Used in Research: A Survey-Based Study
Neufeld, K. J., Nelliot, A., Inouye, S. K., Ely, E. W., Bienvenu, O. J., Lee, H. B., & Needham, D. M. (2014) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2014.03.003 · Cited by 57
Self-citationVochteloo, A. J. H., Moerman, S., van der Burg, B. L. S. B., de Boo, M., de Vries, M. R., Niesten, D. D., Tuinebreijer, W. E., Nelissen, R. G. H. H., & Pilot, P. (2011) · BMC Geriatrics · doi:10.1186/1471-2318-11-39 · Cited by 55 · cited 2×
“Six were RCTs comparing an antipsychotic agent with a placebo; two trials evaluated risperidone,(17,21) in one evaluated olanzapine,(20) and four evaluated haloperidol.(18,19,22,23) Administration of antipsychotics included pre- and postoperative administration in two of the seven studies,(18,20) with one dose given t…”
BackgroundResultProphylactic Antipsychotic Use for Postoperative Delirium
Hirota, T., & Kishi, T. (2013) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.13r08512 · Cited by 49 · cited 1×
“Other outcomes examined in this review, including delirium severity and duration, ICU and hospital LOS, and mortality, were consistent with other analyses that did not demonstrate a significant effect of antipsychotics on these outcomes.(33,37,38) This systematic review and meta-analysis is the most comprehensive in c…”
ResultGilmore, M. L., & Wolfe, D. J. (2013) · General Hospital Psychiatry · doi:10.1016/j.genhosppsych.2012.12.009 · Cited by 47 · cited 1×
“Other outcomes examined in this review, including delirium severity and duration, ICU and hospital LOS, and mortality, were consistent with other analyses that did not demonstrate a significant effect of antipsychotics on these outcomes.(33,37,38) This systematic review and meta-analysis is the most comprehensive in c…”
ResultBell, R. H., Drach, G. W., & Rosenthal, R. A. (2011) · Journal of the American College of Surgeons · doi:10.1016/j.jamcollsurg.2011.08.004 · Cited by 34 · cited 1×
“Participants identified delirium as an essential area in the care of older adults that was poorly understood.(5) Having identified lack of knowledge of delirium as the area of greatest need, the AGS initiated the postoperative delirium clinical practice guideline project.”
BackgroundUnderstanding and Improving Clinical Trial Outcome Measures in Acute Respiratory Failure
Needham, D. M. (2014) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201402-0362ed · Cited by 32
Self-citationBrown, C. H., & Dowdy, D. W. (2014) · Critical Care Medicine · doi:10.1097/ccm.0000000000000665 · Cited by 9
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Dementia prevention, intervention, and care: 2020 report of the Lancet Commission
Livingston, G., Huntley, J., Sommerlad, A., Ames, D., Ballard, C., Banerjee, S., Brayne, C., Burns, A., Cohen-Mansfield, J., Cooper, C., et al. (2020) · The Lancet · doi:10.1016/s0140-6736(20)30367-6 · Cited by 10,430
RetractedWilson, J. E., Mart, M. F., Cunningham, C. M., Shehabi, Y., Girard, T. D., MacLullich, A. M. J., Slooter, A. J. C., & Ely, E. W. (2020) · Nature Reviews Disease Primers · doi:10.1038/s41572-020-00223-4 · Cited by 1,371
Delirium in Hospitalized Older Adults
Marcantonio, E. R. (2017) · New England Journal of Medicine · doi:10.1056/nejmcp1605501 · Cited by 1,228
Delirium in Older Persons: Advances in Diagnosis and Treatment
Oh, E. S., Fong, T. G., Hshieh, T. T., & Inouye, S. K. (2017) · JAMA · doi:10.1001/jama.2017.12067 · Cited by 926
Self-citationPostoperative delirium: perioperative assessment, risk reduction, and management
Jin, Z., Hu, J., & Ma, D. (2020) · British Journal of Anaesthesia · doi:10.1016/j.bja.2020.06.063 · Cited by 705
Metadata
- Authors
- Neufeld, K. J., Yue, J., Robinson, T. N., Inouye, S. K., & Needham, D. M.
- Affiliations
- Johns Hopkins University (US)
- Sichuan University (CN)
- University of Colorado Anschutz (US)
- Beth Israel Deaconess Medical Center (US)
- Corresponding author
- Neufeld, Karin J.
- Venue
- Journal of the American Geriatrics Society
- Publisher
- Wiley
- Published
- 2016-03-23
- Volume
- 64
- Issue
- 4
- Pages
- 705-714
- ISSN
- 0002-8614 (ISSN-L)
- 1532-5415
- PMC
- PMC4840067
- OpenAlex
- W2310520207
- Cited by
- 505
- References
- 46
- Citations by year
- 2026: 29 · 2025: 39 · 2024: 58 · 2023: 52 · 2022: 41 · 2021: 42 · 2020: 59 · 2019: 65 · 2018: 56 · 2017: 49 · 2016: 15
- FWCI
- 9.64
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of the American Geriatrics Society (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- John A. Hartford Foundation (2009–0079)
- National Institute on Aging (K07AG041835, P01AG031720)
- Topics
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Intensive Care Unit Cognitive Disorders
- Health Sciences › Medicine › Clinical Neurology › Alcoholism and Thiamine Deficiency
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Sedative Agents
- Keywords
- antipsychotic drugs, delirium, delirium prevention, delirium management, hospitalized adults, surgical patients, medical inpatients, postoperative delirium, delirium duration, delirium severity, length of hospital stay, mortality, atypical antipsychotics, typical antipsychotics
- MeSH terms
- Adult, Delirium, Hospitalization, Humans, Antipsychotic Agents
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