Highlights
- •Haloperidol prophylaxis may reduce postoperative delirium in selected populations.
- •There are no placebo-controlled trials with haloperidol for delirium treatment.
- •RCTs with haloperidol for hospital delirium management show wide variety in design.
- •Haloperidol use is not associated with a significant increase in side-effects.
- •Trials examining the effects on clinical endpoints such as mortality are lacking.
Abstract
Objective
Haloperidol is generally considered the drug of choice for in-hospital delirium management.
We conducted a systematic review to evaluate the evidence for the efficacy and safety
of haloperidol for the prevention and treatment of delirium in hospitalized patients.
Methods
PubMed, Embase, Cumulative Index to Nursing and Allied Health (CINAHL), PsycINFO,
and the Cochrane Library were systematically searched up to April 21, 2015. We included
English full-text randomized controlled trials using haloperidol for the prevention
or treatment of delirium in adult hospitalized patients reporting on delirium incidence,
duration, or severity as primary outcome. Quality of evidence was graded. Meta-analysis
was not conducted because of between-study heterogeneity.
Results
Twelve studies met our inclusion criteria, four prevention and eight treatment trials.
Methodological limitations decreased the graded quality of included studies. Results
from placebo-controlled prevention studies suggest a haloperidol-induced protective
effect for delirium in older patients scheduled for surgery: two studies reported
a significant reduction in ICU delirium incidence and one study found a significant
reduction in delirium severity and duration. Although placebo-controlled trials are
missing, pharmacological treatment of established delirium reduced symptom severity.
Haloperidol administration was not associated with treatment-limiting side-effects,
but few studies used a systematic approach to identify adverse events.
Conclusion
Although results on haloperidol for delirium management seem promising, current prevention
trials lack external validity and treatment trials did not include a placebo arm on
top of standard nonpharmacological care. We therefore conclude that the current use
of haloperidol for in-hospital delirium is not based on robust and generalizable evidence.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to European Journal of Internal MedicineAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Diagnostic and Statistical Manual of Mental Disorders. Fifth ed. American Psychiatric Association, Arlington, VA2013
- Delirium in elderly people.Lancet. 2014; 383: 911-922
- Delirium in hospitalized elderly patients and post-discharge mortality.Clinics (Sao Paulo). 2010; 65: 251-255
- Longitudinal assessment of serum anticholinergic activity in delirium of the elderly.J Psychiatr Res. 2012; 46: 1339-1345
- One-year health care costs associated with delirium in the elderly population.Arch Intern Med. 2008; 168: 27-32
- Delirium is a risk factor for institutionalization and functional decline in older hip fracture patients.J Psychosom Res. 2014; 76: 68-74
- High risk of cognitive and functional decline after postoperative delirium. A three-year prospective study.Dement Geriatr Cogn Disord. 2008; 26: 26-31
- Delirium in older medical inpatients and subsequent cognitive and functional status: a prospective study.CMAJ. 2001; 165: 575-583
- Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis.JAMA. 2010; 304: 443-451
- Duration of postoperative delirium is an independent predictor of 6-month mortality in older adults after hip fracture.J Am Geriatr Soc. 2014; 62: 1335-1340
- Days of delirium are associated with 1-year mortality in an older intensive care unit population.Am J Respir Crit Care Med. 2009; 180: 1092-1097
- Older adults discharged from the hospital with delirium: 1-year outcomes.J Am Geriatr Soc. 2006; 54: 1245-1250
- The course of delirium in older medical inpatients: a prospective study.J Gen Intern Med. 2003; 18: 696-704
- Consensus and variations in opinions on delirium care: a survey of European delirium specialists.Int Psychogeriatr. 2013; 25: 2067-2075
- A national survey of the management of delirium in UK intensive care units.QJM. 2010; 103: 243-251
- Recognition and management of delirium among doctors, nurses, physiotherapists, and psychologists: an Italian survey.Int Psychogeriatr. 2014; 26: 2093-2102
- Preventing delirium: should non-pharmacological, multicomponent interventions be used? A systematic review and meta-analysis of the literature.Age Ageing. 2015; 44: 196-204
- Pharmacologic prevention and treatment of delirium in critically ill and non-critically ill hospitalised patients: a review of data from prospective, randomised studies.Best Pract Res Clin Anaesthesiol. 2012; 26: 289-309
- Current perceptions and practices surrounding the recognition and treatment of delirium in the intensive care unit: a survey of 250 critical care pharmacists from eight states.Ann Pharmacother. 2011; 45: 1217-1229
U.S. Food and Drug Administration (FDA). 2062. 2013. Ref Type: Internet Communication
- Grading quality of evidence and strength of recommendations.BMJ. 2004; 328: 1490
- The Cochrane Collaboration's tool for assessing risk of bias in randomised trials.BMJ. 2011; 343: d5928
- Olanzapine and haloperidol for senile delirium: a randomized controlled observation.Chin J Clin Rehabil. 2006; 10: 188-190
- An open trial comparing haloperidol with olanzapine for the treatment of delirium in palliative and hospice center cancer patients.J Intern Med Taiwan. 2008; 19: 346-354
- Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomised, double-blind, placebo-controlled trial.Lancet Respir Med. 2013; 1: 515-523
- Novel therapeutic strategies for delirium in patients with cancer: a preliminary study.Am J Hosp Palliat Care. 2014; (Epub ahead of print)
- Olanzapine in the treatment of delirium.Psychosomatics. 1998; 39: 422-430
- Prophylactic consecutive administration of haloperidol can reduce the occurrence of postoperative delirium in gastrointestinal surgery.Yonago Acta Med. 1999; 42: 179-184
- Haloperidol prophylaxis does not prevent postoperative delirium in elderly patients: a randomized, open-label prospective trial.Surg Today. 2014; 44: 2305-2313
- Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized placebo-controlled study.J Am Geriatr Soc. 2005; 53: 1658-1666
- Haloperidol prophylaxis decreases delirium incidence in elderly patients after noncardiac surgery: a randomized controlled trial.Crit Care Med. 2012; 40: 731-739
- Morphine is a reasonable alternative to haloperidol in the treatment of postoperative hyperactive-type delirium after cardiac surgery.J Cardiothorac Vasc Anesth. 2013; 27: 933-938
- A double-blind trial of haloperidol, chlorpromazine, and lorazepam in the treatment of delirium in hospitalized AIDS patients.Am J Psychiatry. 1996; 153: 231-237
- Comparative efficacy study of haloperidol, olanzapine and risperidone in delirium.J Psychosom Res. 2011; 71: 277-281
- A double-blind trial of risperidone and haloperidol for the treatment of delirium.Psychosomatics. 2004; 45: 297-301
- Quetiapine versus haloperidol in the treatment of delirium: a double-blind, randomized, controlled trial.Drug Des Devel Ther. 2013; 7: 657-667
- Does plasma free-3-methoxy-4-hydroxyphenyl(ethylene)glycol increase in the delirious state? A comparison of the effects of mianserin and haloperidol on delirium.Int Clin Psychopharmacol. 1997; 12: 147-152
- Olanzapine vs haloperidol: treating delirium in a critical care setting.Intensive Care Med. 2004; 30: 444-449
- Ondasetron versus haloperidol for the treatment of postcardiotomy delirium: a prospective, randomized, double-blinded study.J Cardiothorac Surg. 2012; 7: 25
- Validation of the Delirium Rating Scale—revised-98: comparison with the delirium rating scale and the cognitive test for delirium.J Neuropsychiatry Clin Neurosci. 2001; 13: 229-242
- Delirium subtype identification and the validation of the Delirium Rating Scale—revised-98 (Dutch version) in hospitalized elderly patients.Int J Geriatr Psychiatry. 2006; 21: 876-882
- Efficacy and safety of haloperidol versus atypical antipsychotic medications in the treatment of delirium.BMC Psychiatry. 2013; 13: 240
- Aripiprazole and haloperidol in the treatment of delirium.Aust N Z J Psychiatry. 2011; 45: 477-482
- Haloperidol and risperidone in the treatment of delirium and its subtypes.Eur J Psychiatry. 2011; 25: 59-67
- Treatment of delirium with quetiapine..Prim Care Companion J Clin Psychiatry. 2000; 2: 10-12
- Feasibility, efficacy, and safety of antipsychotics for intensive care unit delirium: the MIND randomized, placebo-controlled trial.Crit Care Med. 2010; 38: 428-437
- Effect of intravenous haloperidol on the duration of delirium and coma in critically ill patients (Hope-ICU): a randomised, double-blind, placebo-controlled trial.Lancet Respir Med. 2013; 1: 515-523
- Does delirium contribute to poor hospital outcomes? A three-site epidemiologic study.J Gen Intern Med. 1998; 13: 234-242
- Open reduction internal fixation versus hemiarthroplasty versus total hip arthroplasty in the elderly: a review of the National Surgical Quality Improvement Program database.J Surg Res. 2013; 181: 193-198
- Operative intervention for geriatric hip fracture: does type of surgery affect hospital length of stay?.Am J Orthop (Belle Mead NJ). 2015; 44: 228-232
- A review and Bayesian meta-analysis of clinical efficacy and adverse effects of 4 atypical neuroleptic drugs compared with haloperidol and placebo.J Clin Psychopharmacol. 2011; 31: 698-704
- Antipsychotic drugs and QT prolongation.Int Clin Psychopharmacol. 2005; 20: 243-251
- Practice guideline for the treatment of patients with delirium.in: Am J Psychiatry. 156(5 Suppl). American Psychiatric Association, 1999: 1-20
- Consensus and variations in opinions on delirium care: a survey of European delirium specialists.Int Psychogeriatr. 2013; 25: 2067-2075
- NICE clinical guideline 103 delirium diagnosis, prevention and management.2010 (Ref Type: Online Source)
- A national survey of the management of delirium in UK intensive care units.QJM. 2010; 103: 243-251
Article info
Publication history
Published online: November 06, 2015
Accepted:
October 16,
2015
Received in revised form:
October 14,
2015
Received:
July 28,
2015
Identification
Copyright
© 2015 European Federation of Internal Medicine. Published by Elsevier Inc. All rights reserved.
