title: Efficacy and safety of haloperidol for in-hospital delirium prevention and treatment: A systematic review of current evidence.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: VU University Medical Center, Section Acute Medicine, Section Gerontology, Department of Internal Medicine, De Boelelaan 1117, 1007 MB Amsterdam, The Netherlands. Electronic address: ej.schrijver@vumc.nl.
authors.forename: E J M
authors.initials: EJ
authors.lastname: Schrijver
authors.affiliation: VU University Medical Center, Section Acute Medicine, Section Gerontology, Department of Internal Medicine, De Boelelaan 1117, 1007 MB Amsterdam, The Netherlands. Electronic address: k.degraaf@vumc.nl.
authors.forename: K
authors.initials: K
authors.lastname: de Graaf
authors.affiliation: VU University Medical Center, Section Acute Medicine, Section Gerontology, Department of Internal Medicine, De Boelelaan 1117, 1007 MB Amsterdam, The Netherlands. Electronic address: oj.devries@vumc.nl.
authors.forename: O J
authors.initials: OJ
authors.lastname: de Vries
authors.affiliation: VU University Medical Center, Section Acute Medicine, Section Gerontology, Department of Internal Medicine, De Boelelaan 1117, 1007 MB Amsterdam, The Netherlands. Electronic address: a.maier@vumc.nl.
authors.forename: A B
authors.initials: AB
authors.lastname: Maier
authors.affiliation: VU University Medical Center, Section Acute Medicine, Section Gerontology, Department of Internal Medicine, De Boelelaan 1117, 1007 MB Amsterdam, The Netherlands. Electronic address: p.nanayakkara@vumc.nl.
authors.forename: P W B
authors.initials: PW
authors.lastname: Nanayakkara
mesh_terms: D000368:Aged; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D003693:Delirium / Q000188:drug therapy* / Q000517:prevention & control*; D006220:Haloperidol / Q000627:therapeutic use*; D006760:Hospitalization; D006801:Humans; D016032:Randomized Controlled Trials as Topic
chemical_list: D014150:Antipsychotic Agents; D006220:Haloperidol
keywords: Delirium; Elderly; Haloperidol; Prophylaxis; Systematic review; Treatment