Pharmacological Management

The pathophysiology of delirium is not fully understood, and is likely to be complex. [1-3] Pharmacological treatment of delirium has evolved empirically and relies predominantly on antipsychotics. In a palliative situation where there is risk of harm and significant distress to patient and caregivers, sedation may also be a goal of treatment, and sedatives are frequently used. There is little guidance from the literature regarding when antipsychotics should be commenced, how they should be titrated, whether they actually alter the outcomes of the delirium episode, and whether they are equally effective in hypoactive and hyperactive delirium. [4-5]

What is known

Systematic reviews of antipsychotics for the pharmacological management of delirium have been completed. [1, 4-12] The evidence comes mainly from small studies, few of which were done in palliative care populations. Antipsychotics have been studied as both treatment for established delirium and as prophylaxis. Whilst the evidence from systematic reviews suggests a benefit in the treatment of delirium, it is not robust enough to support specific recommendations. Practice therefore continues to be based on expert opinion.

None of the systematic reviews has identified clinically significant differences between haloperidol and atypical antipsychotics. The findings are limited by the lack of placebo-controlled studies. Improvement as a result of the natural history of delirium cannot be excluded.

Limited data from the included studies suggests that haloperidol (at higher doses, i.e., greater than 4.5mg per day) may be associated with slightly more side effects than atypical agents; however few of the studies examined adverse events systematically.

A systematic review specifically focusing on treatment of delirium at the end of life notes that there is no evidence to support the use of benzodiazepines, barbiturates, phenothiazines or propofol in treatment of delirium in palliative care. Nor was any evidence available to support the practices of opioid switching or artificial hydration in treating delirium. [10]

What it means in practice

  • An assessment for delirium should first identify potentially reversible causes and attempt to treat them.
  • Pharmacological management of delirium is at present based on expert opinion and, on that basis, low dose haloperidol can be recommended as first line treatment.
  1. Leonard M, Agar M, Mason C, Lawlor P. Delirium issues in palliative care settings. J Psychosom Res. 2008 Sep;65(3):289-98.
  2. Macleod AD. Delirium: the clinical concept. Palliat Support Care. 2006 Sep;4(3):305-12.
  3. Inouye SK, Ferrucci L. Elucidating the pathophysiology of delirium and the interrelationship of delirium and dementia. J Gerontol A Biol Sci Med Sci. 2006 Dec;61(12):1277-80.
  4. Bourne RS, Tahir TA, Borthwick M, Sampson EL. Drug treatment of delirium: past, present and future. J Psychosom Res. 2008 Sep;65(3):273-82.
  5. Gagnon PR. Treatment of delirium in supportive and palliative care. Curr Opin Support Palliat Care. 2008 Mar;2(1):60-6.
  6. Candy B, Jackson KC, Jones L, Leurent B, Tookman A, King M. Drug therapy for delirium in terminally ill patients. Cochrane Database Syst Rev. 2012 Nov 14;11:CD004770.
  7. Seitz DP, Gill SS, van Zyl LT. Antipsychotics in the treatment of delirium: a systematic review. J Clin Psychiatry. 2007 Jan;68(1):11-21.
  8. Lonergan E, Britton AM, Luxenberg J, Wyller T. Antipsychotics for delirium. Cochrane Database Syst Rev. 2007 Apr 18;(2):CD005594.
  9. Keeley P. Delirium at the end of life. Clin Evid (Online). 2007 Jun 1;2007. pii: 2405.
  10. Lacasse H, Perrault MM, Williamson DR. Systematic review of antipsychotics for the treatment of hospital-associated delirium in medically or surgically ill patients. Ann Pharmacother. 2006 Nov;40(11):1966-73. Epub 2006 Oct 17.
  11. Peritogiannis V, Stefanou E, Lixouriotis C, Gkogkos C, Rizos DV. Atypical antipsychotics in the treatment of delirium. Psychiatry Clin Neurosci. 2009 Oct;63(5):623-31. Epub 2009 Aug 10.
  12. Campbell N, Boustani MA, Ayub A, Fox GC, Munger SL, Ott C, Guzman O, Farber M, Ademuyiwa A, Singh R. Pharmacological management of delirium in hospitalized adults--a systematic evidence review. J Gen Intern Med. 2009 Jul;24(7):848-53. Epub 2009 May 8.


  • Delirium Clinical Care Standard
    Australian Commission on Safety and Quality in Health Care. Delirium Clinical Care Standard. Sydney: ACSQHC, 2016.
    This Clinical Care Standard describes the clinical care that a patient with delirium should be offered.
  • Delirium: diagnosis, prevention and management
    NICE clinical guideline 103. London: National Institute of Health and Clinical Excellence; 2010.
    Includes: Full guideline documents, Quick reference guide, NICE guidance written for patients and carers
  • Delirium Care Pathways (Commonwealth of Australia 2011) (463kb pdf)
    Developed by Associate Professor Victoria Traynor and Nicole Britten, University of Wollongong, under the management of the New South Wales Department of Health, on behalf of the Health Care of Older Australians Standing Committee

Link to prescribing information

Overview article

Last updated 18 January 2017