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

• Several systematic reviews of antipsychotics for the pharmacological management of delirium have been completed. [1, 6-11] The evidence comes from a small number of studies, few of which were done in palliative care populations. Antipsychotics have been studied as both treatment for established delirium and as prophylaxis. The evidence from systematic reviews is not robust enough to support any specific pharmacological treatments, and 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, ie, 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 found 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. 

Finding out more
Guidelines

• Clinical Practice Guidelines for the Management of Delirium in Older People 
  Clinical Epidemiology & Health Services Evaluation Unit, Melbourne Health in collaboration with the Delirium Clinical Guidelines Expert Working Group. Clinical Practice Guidelines for the Management of Delirium in Older People. Melbourne: AHMAC Health Care of Older Australians Standing Committee; 2006.

Link to prescribing information
NB Prescribing information may not yet have been updated to include the most recent evidence.

• Online Palliative Medicine Handbook 
  Click on “Notes on Prescribing”
  This prescribing information is from the UK and some medications may not be available in Australia
• Therapeutic Guidelines for Palliative Care
  An Australian source of prescribing information not available directly online through CareSearch, but can be accessed online in most hospitals, or purchased

Overview article

• Diagnosis and management of delirium near the end of life
  Casarett DJ, Inouye SK. Diagnosis and management of delirium near the end of life. Annals of Internal Medicine. 2001 Jul 3;135(1):32-40.

Related CareSearch pages
End-of-life care
Depression
Suffering
Review Collection: Delirium

References

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. Palliative and Supportive Care. 2006 Sep;4(3):305-12   
3.  Inouye SK, Ferrucci L. Elucidating the pathophysiology of delirium and the interrelationship of delirium and dementia. The Journals of Gerontology. Series A, biological sciences and medical sciences. 2006 Dec;61(12):1277-80 [no abstract available].  
4. Lawlor P, Fainsinger R, Bruera E. Delirium at the end of life: critical issues in clinical practice and research. JAMA. 2000 Nov 15;284(19):2427-9. [no abstract available]. 
5. Friedlander MM, Brayman Y, Breitbart WS. Delirium in palliative care. Oncology 2004 Oct;18(12):1541-53.  
6. Jackson KC, Lipman AG. Drug therapy for delirium in terminally ill patients. Cochrane Database of Systematic Reviews. 2004;(2):CD004770.  
7. Seitz DP, Gill SS, van Zyl LT. Antipsychotics in the treatment of delirium: a systematic review. Journal of Clinical Psychiatry. 2007 Jan;68(1):11-21.
8. Lonergan E, Britton AM, Luxenberg J, Wyller T. Antipsychotics for delirium. Cochrane Database of Systematic Reviews, 2007(2): p. CD005594. 
9. Keeley P. Delirium at the end of life. BMJ Clinical Evidence. 2008. 
10. Lacasse H, Perrault MM, Williamson DR. Systematic review of antipsychotics for the treatment of hospital associated delirium in medically or surgically ill patients. Annals of Pharmacotherapy. 2006 Nov;40(11):1966-73. 

This page was created on 2 September 2008 and is due for review in September 2010
Last updated 30 September 2008