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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 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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Items 201–300 of 504
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“Antipsychotics, historically used by psychiatrists to treat psychotic and mood disorders, have been extensively studied for delirium because of the similar clinical presentations, as delirious patients often exhibit psychosis, impulsivity, and emotional disturbances [9].”
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Philosophy of too much medicine conference report
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Prävention des Delirs auf der Intensivstation
Braune, S. A., & Gurlit, S. (2019) · DMW - Deutsche Medizinische Wochenschrift · doi:10.1055/a-0666-3947 · Cited by 6
“Die aktuelle Studienlage zur Gabe von Melatonin zur Stabilisierung des Tag-Nacht-Rhythmus bei Intensivpatienten ist schwach [31, 32].”
BackgroundInfluentialNew Insights into the Future of Pharmacoepidemiology and Drug Safety
Herdeiro, M. T., Roque, F., Figueiras, A., & Silva, T. M. (2021) · IntechOpen eBooks · doi:10.5772/intechopen.87642 · Cited by 6
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“Even if haloperidol efficacy is still debated (Neufeld et al., 2016), a 2017 study underlines that in treating the syndrome up to 58% of clinicians do not follow defined protocols or guidelines, and 65% use haloperidol (Morandi et al., 2017).”
BackgroundPostoperatives Delir im Aufwachraum
Rudy, M., & Saller, T. (2023) · Die Anaesthesiologie · doi:10.1007/s00101-023-01281-5 · Cited by 5
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“However, current evidence does not support the use of antipsychotics for the prevention of delirium, and antipsychotics have not been shown to improve delirium duration or severity.(22) From our current results, it is unclear if the AMTS specifically helps with the management of delirium in the acute orthopedic patien…”
ResultDelirium in Older Adults: What a Surgeon Needs to Know
Melegari, G., Gaspari, A., Gualdi, E., Zoli, M., Meletti, S., & Barbieri, A. (2022) · Surgeries · doi:10.3390/surgeries3010006 · Cited by 5
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BackgroundPrinciples of Geriatric Pharmacotherapy
Devlin, J. W., & Barletta, J. F. (2018) · Cambridge University Press eBooks · doi:10.1017/9781316676325.004 · Cited by 5
Management des Delirs auf der Intensivstation
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“Melatonin zur Förderung des Tag-Nacht-Rhythmus Die aktuelle Studienlage zur Gabe von Melatonin zur Stabilisierung des Tag-Nacht-Rhythmus bei Intensivpatienten ist schwach und beschränkt sich meist auf postoperative Intensivpatienten [2].”
BackgroundInfluentialDoes this critically ill patient with delirium require any drug treatment?
Salluh, J. I., & Latronico, N. (2018) · Intensive Care Medicine · doi:10.1007/s00134-018-5310-x · Cited by 5
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“A meta-analysis by Neufeld et al (2016) found no improvement in outcomes with antipsychotics in either prevention or treatment of delirium.”
MethodThe Hospital Elder Life Program: Past and Future
Scheunemann, L. P., Girard, T. D., Skidmore, E. R., & Resnick, N. M. (2018) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2018.08.002 · Cited by 5
“to few, in any, medications with widespread efficacy in the prevention and treatment of delirium.(3) Unlike a medication, which would theoretically work by targeting a final common mechanistic pathway of delirium, HELP targets multiple environmental factors (e.”
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“[142] Melatonin and melatonin receptor agonists, such as ramelt-eon, have been studied for their potential role in the treatment of POD, given their involvement in the regulation of sleep-wake cycles.”
Delirium in cardiovascular medicine
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Deliryum yönetiminde farmakolojik olmayan hemşirelik yaklaşımlarının değerlendirilmesi
ASLANGÜL, S., Ayhan, F., & Terzioğlu, C. (2022) · Mersin üniversitesi sağlık bilimleri dergisi/Mersin üniversitesi sağlık bilimleri dergisi · doi:10.26559/mersinsbd.1051142 · Cited by 4
Is There a Role for Medication in Managing Delirium with Dementia?
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“Additionally, several studies have shown no significant differences in the safety outcomes among various antipsychotics when used for delirium management [33–35].”
BackgroundResultDelirium Superimposed on Dementia
Apold, S. (2018) · The Journal for Nurse Practitioners · doi:10.1016/j.nurpra.2017.12.010 · Cited by 4
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“However, the role of psychotropics or antipsychotics in the management of delirium is increasingly being questioned (Neufeld et al., 2016; Agar et al., 2017).”
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“Extending the previous work within and outside the field of palliative care (16, 17, 30), our study further supports the proposal that individualized treatment of underlying precipitants should remain the key approach in the management of delirium among palliative care patients, and JOURNAL OF PAIN & PALLIATIVE CARE P…”
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“To date, however, conclusive evidence of the effectiveness of pharmacological prevention or treatment of delirium is lacking [2,10].”
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Psychopharmacology and pharmacokinetics
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“Current literature does not support the prescription of antipsychotics [10] and benzodiazepines [11] for the treatment of delirium in hospitalized patients.”
BackgroundAnalgesia, Sedation, Paralytics, Delirium, and Iatrogenic Withdrawal
Valentine, K. M., & Kummick, J. (2022) · Pediatric Clinics of North America · doi:10.1016/j.pcl.2022.01.012 · Cited by 4
Delirium in the Terminally Ill
Manschreck, C., Alici, Y., & BREITBART, W. S. (2022) · Oxford University Press eBooks · doi:10.1093/med/9780197583838.003.0006 · Cited by 4
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Amirfarzan, H., Schumann, R., & Leissner, K. B. (2025) · Drugs & Aging · doi:10.1007/s40266-025-01224-2 · Cited by 3
“One study compared enteral olanzapine with enteral haloperidol for treating ICU patients with delirium, finding no significant difference in delirium development between groups, while olanzapine was associated with fewer extrapy-ramidal symptoms [67].”
Nwosu, A. D. G., Ossai, E. N., Nganwuchu, C. C., Ahaotu, F. N., & Duru, N. E. (2025) · Patient Safety in Surgery · doi:10.1186/s13037-025-00439-x · Cited by 3
“The use of antipsychotics for the prevention or treatment of post-operative delirium is of unproven benefit in improving outcomes [14].”
The Neuropsychiatric Disturbances of Delirium: A Review of Syndromes and Their Treatment
Lee, S., Ro, G. S., Weber, M. T., & Oldham, C. M. (2025) · American Journal of Geriatric Psychiatry · doi:10.1016/j.jagp.2025.10.003 · Cited by 3
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“Pharmacological prophylaxis remains controversial, with numerous agents investigated yielding inconsistent results [8, 9].”
Sánchez, A., Sawant-Uttekar, P., Pribadi, A. N., Heinen, D., Thomas, C., Arnim, C. A. F. V., Kühnle, J., Kreisel, S. H., Hewer, W., Fath, B., et al. (2026) · Age and Ageing · doi:10.1093/ageing/afag085 · Cited by 3
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“With heterogenous patient characteristics, this meta-analysis was unable to generalize its findings to older adult and palliative care populations.(19) A recent randomized, doubleblind, controlled trial investigated the use of haloperidol or risperidone in the palliative care setting, though again did not show any eff…”
BackgroundResultBeretta, M., Uggeri, S., Santucci, C., Cattaneo, M., Ermolli, D., Gerosa, C., Ornaghi, M., Roccasalva, A., Santambrogio, P., Varrassi, G., et al. (2022) · Cureus · doi:10.7759/cureus.25706 · Cited by 3
“A meta-analysis [15] found that antipsychotics had no significant effects on delirium duration, severity, and mortality in patients with 1 2 3 4 5 4 4 4 4 6 7 Open Access Original Article DOI: 10.”
BackgroundThirty-day mortality among patients with acute delirium in the emergency department
Sanguanwit, P., Ninlamal, S., & Prachanukool, T. (2023) · Heliyon · doi:10.1016/j.heliyon.2023.e20554 · Cited by 3
“Pharmacological interventions, such as antipsychotics and atypical psychotics, may be added to non-pharmacological approaches to reduce severity, although they do not impact mortality outcomes [23].”
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“20,21 Additionally, a U.S. study found that Older Adults patients with a history of hospital admissions (OR 2.93 [95% CI: 2.71-3.18]) and those attending outpatient clinics more than 12 times a year (OR 2.66 [95% CI: 1.92-3.69]) were at an increased risk for repeat visits to the ED.”
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HIV-Associated Neurocognitive Disorders and Delirium
Hirsch, C. H., Stewart, A. L., Sales, P. M. G., Pereira, L. F., & Bourgeois, J. A. (2021) · Springer eBooks · doi:10.1007/978-3-030-80665-1_10 · Cited by 3
Recognizing and Acting on Mentation Concerns
Mack, L., Zonsius, M. C., Newman, M., & Emery‐Tiburcio, E. E. (2022) · AJN American Journal of Nursing · doi:10.1097/01.naj.0000830764.74949.fd · Cited by 3
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Pharmakologisches Management des postoperativen Delir
Vasiljewa, L., Müller, A., & Spies, C. (2023) · AINS - Anästhesiologie · Intensivmedizin · Notfallmedizin · Schmerztherapie · doi:10.1055/a-2065-3780 · Cited by 3
“Außerdem wirkte sich das POD bei herzchirurgischen Patient*innen auf die Dauer des Aufenthalts auf der Intensivstation und bei allen chirurgischen Patient*innen auf die Dauer des Krankenhausaufenthalts aus.”
BackgroundInfluentialBalasundaram, B., Loh, S. Y., Rosario, B. H., Tun, M. H., Ooi, C. H., Li, F., & Bishara, D. (2023) · Delirium · doi:10.56392/001c.87943 · Cited by 3
Herranz, J. F., Pancorbo, A. G.-E., Gil, A., & Blanco, I. M. (2023) · Medicine - Programa de Formación Médica Continuada Acreditado · doi:10.1016/j.med.2023.11.002 · Cited by 3
Prise en charge du délirium chez les personnes âgées à l’urgence
Mailhot, T., Baelen, S., Maheu‐Cadotte, M., Fontaine, G., Cossette, S., & Lavoie, P. (2023) · Soins d’urgence La revue de l’Association des infirmières et infirmiers d’urgence du Québec · doi:10.7202/1101856ar · Cited by 3
“Finalement, mentionnons que les traitements médicamenteux ne permettent pas de guérir le délirium, mais seulement d’en diminuer les symptômes ou d’en traiter la cause [53, 54].”
BackgroundMachado‐Duque, M. E., Camacho-Arteaga, L., Sabaté, M., Vidal, X., & Machado‐Alba, J. E. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1369200 · Cited by 3
Naeem, F., Penfold, R., Soiza, R. L., von Haken, R., Lindroth, H. L., Liu, K., Nydhal, P., & Quinn, T. (2024) · The Journal of the Royal College of Physicians of Edinburgh · doi:10.1177/14782715241301486 · Cited by 3
“16,22,24 25–28 National guidelines suggest that if commenced, antipsychotics should be reviewed daily and stopped as soon as the clinical situation allows, typically within 1–2 days.”
Park, J., Oh, J., Park, S., Choi, W., Shin, C. S., Na, S. H., Kim, J., Oh, J., & Park, J. Y. (2018) · Acute and Critical Care · doi:10.4266/acc.2017.00584 · Cited by 3
“It may also be difficult to correct the cause of delirium because there are no proven pharmacological [1] or nonpharmacological treatments [2] after delirium has occurred.”
BackgroundDas Delir — Klinik, Pathogenese, Therapie und Prävention
Mann, K. (2018) · InFo Neurologie + Psychiatrie · doi:10.1007/s15005-018-2372-9 · Cited by 3
“Mehrere Untersuchungen haben günstige Effekte auf Dauer und Schwere von Delirien gefunden, andererseits wurden auch negative Befunde berichtet, insbesondere gibt es keine klare Evidenz für einen Nutzen bezüglich des klinischen Outcomes, wie Länge des stationären Aufenthaltes oder Dauer intensivmedizinischer Behandlung…”
Pediatric Delirium Assessment, Prevention, and Management
Smith, H. A. B., & Williams, S. R. (2020) · Springer eBooks · doi:10.1007/978-3-030-25751-4_6 · Cited by 3
Characteristics of Inpatients Prescribed Dopamine Receptor Blocking Agents
Schwartz, S. E., Dinkla, L., Pullen, J., Bernard, R., & Kumar, A. (2025) · Psychopharmacology Bulletin · doi:10.64719/pb.4418 · Cited by 3
Merel, S. E., Lee, T. Y. M., & White, A. A. (2019) · Springer eBooks · doi:10.1007/978-3-030-19704-9_53 · Cited by 3
Scott, D. A., & Evered, L. A. (2019) · Anaesthesia · doi:10.1111/anae.14473 · Cited by 3
“Despite this, many clinicians rely on pharmacological interventions which have been shown to be ineffective, and may in fact be deleterious [11].”
BackgroundDonthu, R. K., Minz, S. M., Spoorthy, M. S., Dyuthy, R., Balaji, A., Sethu, P. S., Varghese, L. B., Ameen, S., Sathian, B., & Menon, V. (2025) · General Hospital Psychiatry · doi:10.1016/j.genhosppsych.2025.10.011 · Cited by 2
Szczupak, M., Kobak, J., Wierzchowska, J., Dąbrowska, A., Mędrzycka-Dąbrowska, W. A., & Krupa, S. (2026) · Journal of Clinical Medicine · doi:10.3390/jcm15072478 · Cited by 2
Central Nervous System Care in Postoperative Adult Cardiac Surgery
Dabbagh, A. (2018) · Springer eBooks · doi:10.1007/978-3-319-75747-6_12 · Cited by 2
Delirium: Risk Factors, Contributors, Identification, Work-Up, and Treatment
Lau, T., Kozyra, E., & Cheng, C. M. C. (2019) · Springer eBooks · doi:10.1007/978-3-030-10401-6_12 · Cited by 1
Akinjogbin, T., Parnell, J. M., & Duggan, M. C. (2020) · OBM Geriatrics · doi:10.21926/obm.geriatr.2003128 · Cited by 2
Preventing PICS with the ABCDEF Bundle
Leonard, K. M., Mart, M. F., & Ely, E. W. (2021) · Springer eBooks · doi:10.1007/978-3-030-68680-2_1 · Cited by 3
Palliative medicine and care of the elderly
Agar, M. R., & Phillips, J. L. (2021) · doi:10.1093/med/9780198821328.003.0099 · Cited by 2
Joshi, P., & Tampi, R. R. (2022) · Springer eBooks · doi:10.1007/978-3-030-94960-0_26 · Cited by 2
Current status of perioperative management for elderly patients
拓朗, 斎., 添田, 暢., 樋口光徳, 押部郁朗, 渡部晶之, & 根本, 鉄. (2017) · Nippon Ronen Igakkai Zasshi Japanese Journal of Geriatrics · doi:10.3143/geriatrics.54.299 · Cited by 2
Agar, M. R., Alici, Y., Caraceni, A. T., & BREITBART, W. S. (2021) · doi:10.1093/med/9780198821328.003.0074 · Cited by 2
A demenciaellátás innovatív irányai
Dallos, R. G. (2022) · Máltai Tanulmányok · doi:10.56699/mt.2022.4.7 · Cited by 2
Delirium Due to Potentially Avoidable Hospitalizations Among Older Adults
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Igwe, E. O., Nealon, J. R., O’Shaughnessy, P., Ormonde, C., & Traynor, V. (2024) · Australian Journal of Rural Health · doi:10.1111/ajr.13097 · Cited by 2
Qiu, X., Wang, L., Wen, X., Meng, Q., Qi, J., Li, C., Yin, H., Ling, F., Qiao, Y., Zhang, W., et al. (2024) · BMJ Open · doi:10.1136/bmjopen-2024-088163 · Cited by 2
Leroy, S., Bublitz, V., Grittner, U., Fleischmann, R., von Dincklage, F., & Antonenko, D. (2025) · Trials · doi:10.1186/s13063-024-08699-1 · Cited by 2
“The evidence on the benefit of medication is limited and the use of antipsychotics is not a causal treatment of delirium, but only serves to control symptoms (13).”
BackgroundDelirium Prevention and Management in Older Adults in the Emergency Department
Skains, R. M., Lee, S., & Han, J. H. (2025) · Emergency Medicine Clinics of North America · doi:10.1016/j.emc.2024.08.007 · Cited by 3
Continuous intrathecal morphine infusion for pain management in a patient with burn injury
Zuehl, A. R., Ainsworth, C., Chong, J. K., & Benson, C. (2018) · Burns Open · doi:10.1016/j.burnso.2018.08.001 · Cited by 2
Benzodiazepines for treatment of delirium in non-ICU settings
Jin, Y. H., Li, N., Zheng, R., Mu, W., Lei, X., Jin, H., Chen, J., & Shang, H. C. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd012670 · Cited by 2
Geriatrics Literature 2016 Year in Review
Willham, K., Covinsky, K. E., & Widera, E. (2017) · Journal of the American Geriatrics Society · doi:10.1111/jgs.15064 · Cited by 2
“Results are not generalizable beyond persons near the end of life, although a recent systematic review and meta-analysis suggested that antipsychotics do not improve outcomes when used for prevention or treatment of delirium in hospitalized adults.(3) Implications: Antipsychotics may worsen delirium symptoms in indivi…”
Result
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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