Evidence summary

The pathophysiology of delirium is not fully understood and is likely to be complex. [1,2] Pharmacological treatment of delirium has evolved empirically and relies predominantly on antipsychotics. [3] In a palliative care setting where there is risk of harm and significant distress to patient and caregivers, light sedation may also be a goal of treatment in the short term, and sedatives are frequently used.

Systematic reviews of antipsychotics for the pharmacological management of delirium have been completed. [1-5] 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. None of the systematic reviews has identified clinically significant differences between haloperidol and atypical antipsychotics, such as risperidone, clozapine or quetiapine. [2,3] The choice should be made based on individual response. The findings are limited by the lack of placebo-controlled studies.

A recent systematic review specifically focusing on treatment of delirium in palliative care patients notes that there is evidence to support the use of pharmacologic al treatment in moderate to severe delirium. This review supported the use of benzodiazepines, with haloperidol in agitated delirium. [2]

Practice implications

  • An assessment for delirium should first identify potentially reversible causes and attempt to treat them.
  • Pharmacological management of delirium is recommended in moderate to serve delirium. There is no significant difference between haloperidol, olanzapine or risperidone and so choice of medication should be based on the individual response. [2]
  • There are conflicting recommendations about the pharmacological management of agitated delirium in the terminal stages. A recent review of medications at the end of life noted there is limited research on agitated delirium and the evidence that exists is of low quality so recommendations cannot be made. [6] However, another systematic review does suggest thatin agitated delirium, benzodiazepines may be added to haloperidol. [2]

  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. Skelton L, Guo P. Evaluating the effects of the pharmacological and nonpharmacological interventions to manage delirium symptoms in palliative care patients: systematic review. Curr Opin Support Palliat Care. 2019 Sep 3. doi: 10.1097/SPC.0000000000000458. [Epub ahead of print]
  3. Johnson RJ 3rd. A research study review of effectiveness of treatments for psychiatric conditions common to end-stage cancer patients: needs assessment for future research and an impassioned plea. BMC Psychiatry. 2018 Apr 3;18(1):85. doi: 10.1186/s12888-018-1651-9.
  4. 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.
  5. Candy B, Jackson KC, Jones L, Leurent B, Tookman A, King M. Drug therapy for delirium in terminally ill adult patients. Cochrane Database Syst Rev. 2012 Nov 14;11:CD004770. doi: 10.1002/14651858.CD004770.pub2.
  6. Jansen K, Haugen DF, Pont L, Ruths S. Safety and Effectiveness of Palliative Drug Treatment in the Last Days of Life-A Systematic Literature Review. J Pain Symptom Manage. 2018 Feb;55(2):508-521.e3. doi: 10.1016/j.jpainsymman.2017.06.010. Epub 2017 Aug 10.

Last updated 27 August 2021