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Meta-Analysis
. 2020 Jan 21;1(1):CD004770.
doi: 10.1002/14651858.CD004770.pub3.

Drug therapy for delirium in terminally ill adults

Anne M Finucane  1   2 , Louise Jones  3 , Baptiste Leurent  4 , Elizabeth L Sampson  3 , Patrick Stone  3 , Adrian Tookman  5 , Bridget Candy  3
Affiliations
Meta-Analysis

Drug therapy for delirium in terminally ill adults

Anne M Finucane et al. Cochrane Database Syst Rev. .

Abstract

Background: Delirium is a syndrome characterised by an acute disturbance of attention and awareness which develops over a short time period and fluctuates in severity over the course of the day. It is commonly experienced during inpatient admission in the terminal phase of illness. It can cause symptoms such as agitation and hallucinations and is distressing for terminally ill people, their families and staff. Delirium may arise from any number of causes and treatment should aim to address these causes. When this is not possible, or treatment is unsuccessful, drug therapy to manage the symptoms may become necessary. This is the second update of the review first published in 2004.

Objectives: To evaluate the effectiveness and safety of drug therapies to manage delirium symptoms in terminally ill adults.

Search methods: We searched CENTRAL, MEDLINE, Embase, CINAHL and PsycINFO from inception to July 2019, reference lists of retrieved papers, and online trial registries.

Selection criteria: We included randomised controlled trials of drug therapies in any dose by any route, compared to another drug therapy, a non-pharmacological approach, placebo, standard care or wait-list control, for the management of delirium symptoms in terminally ill adults (18 years or older).

Data collection and analysis: We independently screened citations, extracted data and assessed risk of bias. Primary outcomes were delirium symptoms; agitation score; adverse events. Secondary outcomes were: use of rescue medication; cognitive status; survival. We applied the GRADE approach to assess the overall quality of the evidence for each outcome and we include eight 'Summary of findings' tables.

Main results: We included four studies (three new to this update), with 399 participants. Most participants had advanced cancer or advanced AIDS, and mild- to moderate-severity delirium. Meta-analysis was not possible because no two studies examined the same comparison. Each study was at high risk of bias for at least one criterion. Most evidence was low to very low quality, downgraded due to very serious study limitations, imprecision or because there were so few data. Most studies reported delirium symptoms; two reported agitation scores; three reported adverse events with data on extrapyramidal effects; and none reported serious adverse events. 1. Haloperidol versus placebo There may be little to no difference between placebo and haloperidol in delirium symptoms within 24 hours (mean difference (MD) 0.34, 95% confidence interval (CI) -0.07 to 0.75; 133 participants). Haloperidol may slightly worsen delirium symptoms compared with placebo at 48 hours (MD 0.49, 95% CI 0.10 to 0.88; 123 participants with mild- to moderate-severity delirium). Haloperidol may reduce agitation slightly compared with placebo between 24 and 48 hours (MD -0.14, 95% -0.28 to -0.00; 123 participants with mild- to moderate-severity delirium). Haloperidol probably increases extrapyramidal adverse effects compared with placebo (MD 0.79, 95% CI 0.17 to 1.41; 123 participants with mild- to moderate-severity delirium). 2. Haloperidol versus risperidone There may be little to no difference in delirium symptoms with haloperidol compared with risperidone within 24 hours (MD -0.42, 95% CI -0.90 to 0.06; 126 participants) or 48 hours (MD -0.36, 95% CI -0.92 to 0.20; 106 participants with mild- to moderate-severity delirium). Agitation scores and adverse events were not reported for this comparison. 3. Haloperidol versus olanzapine We are uncertain whether haloperidol reduces delirium symptoms compared with olanzapine within 24 hours (MD 2.36, 95% CI -0.75 to 5.47; 28 participants) or 48 hours (MD 1.90, 95% CI -1.50 to 5.30, 24 participants). Agitation scores and adverse events were not reported for this comparison. 4. Risperidone versus placebo Risperidone may slightly worsen delirium symptoms compared with placebo within 24 hours (MD 0.76, 95% CI 0.30 to 1.22; 129 participants); and at 48 hours (MD 0.85, 95% CI 0.32 to 1.38; 111 participants with mild- to moderate-severity delirium). There may be little to no difference in agitation with risperidone compared with placebo between 24 and 48 hours (MD -0.05, 95% CI -0.19 to 0.09; 111 participants with mild- to moderate-severity delirium). Risperidone may increase extrapyramidal adverse effects compared with placebo (MD 0.73 95% CI 0.09 to 1.37; 111 participants with mild- to moderate-severity delirium). 5. Lorazepam plus haloperidol versus placebo plus haloperidol We are uncertain whether lorazepam plus haloperidol compared with placebo plus haloperidol improves delirium symptoms within 24 hours (MD 2.10, 95% CI -1.00 to 5.20; 50 participants with moderate to severe delirium), reduces agitation within 24 hours (MD 1.90, 95% CI 0.90 to 2.80; 52 participants), or increases adverse events (RR 0.70, 95% CI -0.19 to 2.63; 31 participants with moderate to severe delirium). 6. Haloperidol versus chlorpromazine We are uncertain whether haloperidol reduces delirium symptoms compared with chlorpromazine at 48 hours (MD 0.37, 95% CI -4.58 to 5.32; 24 participants). Agitation scores were not reported. We are uncertain whether haloperidol increases adverse events compared with chlorpromazine (MD 0.46, 95% CI -4.22 to 5.14; 24 participants). 7. Haloperidol versus lorazepam We are uncertain whether haloperidol reduces delirium symptoms compared with lorazepam at 48 hours (MD -4.88, 95% CI -9.70 to 0.06; 17 participants). Agitation scores were not reported. We are uncertain whether haloperidol increases adverse events compared with lorazepam (MD -6.66, 95% CI -14.85 to 1.53; 17 participants). 8. Lorazepam versus chlorpromazine We are uncertain whether lorazepam reduces delirium symptoms compared with chlorpromazine at 48 hours (MD 5.25, 95% CI 0.38 to 10.12; 19 participants), or increases adverse events (MD 7.12, 95% CI 1.08 to 15.32; 18 participants). Agitation scores were not reported.

Secondary outcomes: use of rescue medication, cognitive impairment, survival There were insufficient data to draw conclusions or assess GRADE.

Authors' conclusions: We found no high-quality evidence to support or refute the use of drug therapy for delirium symptoms in terminally ill adults. We found low-quality evidence that risperidone or haloperidol may slightly worsen delirium symptoms of mild to moderate severity for terminally ill people compared with placebo. We found moderate- to low-quality evidence that haloperidol and risperidone may slightly increase extrapyramidal adverse events for people with mild- to moderate-severity delirium. Given the small number of studies and participants on which current evidence is based, further research is essential.

PubMed Disclaimer

Conflict of interest statement

AMF: none known.

LJ: none known.

BL: none known.

ELS: none known. ELS is a consultant in Liaison Psychiatry and manages people with delirium in an acute hospital.

PS: none known. PS is a consultant in palliative medicine and manages patients with terminal illness.

AT: none known. AT is a specialist palliative care physician and manages patients with terminal illness.

BC: none known.

Figures

1
1
Review flow diagram.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Agar 2017 {published data only}
    1. Agar MR, Lawlor PG, Quinn S, Draper B, Caplan GA, Rowett D, et al. Efficacy of oral risperidone, haloperidol, or placebo for symptoms of delirium among patients in palliative care: a randomized clinical trial. JAMA Internal Medicine 2017;177(1):34‐42. [DOI: 10.1001/jamainternmed.2016.7491] - DOI - PubMed
Breitbart 1996 {published data only}
    1. Breitbart W, Rocco M, Platt M, Weissman H, Derevenco M, Grau C, et al. A double‐blind trial of haloperidol, chlorpromazine, and lorazepam in the treatment of delirium in hospitalized AIDS patients. American Journal of Psychiatry 1996;153(2):231‐7. - PubMed
Hui 2017 {published data only}
    1. Hui D, Frisbee‐Hume S, Wilson A, Dibaj SS, Thuc N, Cruz M, et al. Effect of lorazepam with haloperidol vs haloperidol alone on agitated delirium in patients with advanced cancer receiving palliative care: a randomized clinical trial. Journal of the American Medical Association 2017;318(11):1047‐56. [DOI: 10.1001/jama.2017.11468] - DOI - PMC - PubMed
Lin 2008 {published data only}
    1. Lin CJ, Sun FJ, Chun‐Kai F, Chen HW, Lai YL. An open trial comparing haloperidol with olanzapine for the treatment of delirium in palliative and hospice center cancer patients. Journal of Internal Medicine of Taiwan 2008;19(4):346‐54. [www.researchgate.net/publication/242741369]

References to studies excluded from this review

Ather 1986 {published data only}
    1. Ather SA, Shaw SH, Stoker MJ. A comparison of chlormethiazole and thioridazine in agitated confusional states of the elderly. Acta Psychiatrica Scandinavica 1986;73(Suppl 329):81‐91. - PubMed
Auchus 1997 {published data only}
    1. Auchus AP, Bissey‐Black C. Pilot study of haloperidol, fluoxetine, and placebo for agitation in Alzheimer's disease. Journal of Neuropsychiatry and Clinical Neurosciences 1997;9(4):591‐3. - PubMed
Boettger 2011a {published data only}
    1. Boettger S, Friedlander M, Breitbart W, Passik S. Aripiprazole and haloperidol in the treatment of delirium. Australian and New Zealand Journal of Psychiatry 2011;45(6):477‐82. - PubMed
Boettger 2011b {published data only}
    1. Boettger S, Breitbart W, Passik S. Haloperidol and risperidone in the treatment of delirium and its subtypes. European Journal of Psychiatry 2011;25(2):59‐67.
Boettger 2015 {published data only}
    1. Boettger S, Jenewein J, Breitbart W. Haloperidol, risperidone, olanzapine and aripiprazole in the management of delirium: a comparison of efficacy, safety, and side effects. Palliative & Supportive Care 2015;13(4):1079‐85. - PubMed
Breitbart 2002 {published data only}
    1. Breitbart W, Tremblay A, Gibson C. An open trial of olanzapine for the treatment of delirium in hospitalized cancer patients. Psychosomatics 2002;43(3):175‐82. - PubMed
Clayton‐Chubb 2016 {published data only}
    1. Clayton‐Chubb D, Lange P. Moderate dose melatonin for the abatement and treatment of delirium in elderly general medical inpatients: study protocol of a placebo controlled, randomised, double blind trial. BMC Geriatrics 2016;16(1):54. - PMC - PubMed
Djokic 2008 {published data only}
    1. Djokic G, Zivkovic N, Pavicevic D, Lazic D, Djokic K, Marjanovic V. Risperidone vs. haloperidol in treatment of delirium superimposed on dementia. European Neuropsychopharmacology 2008;18:S504‐5.
Ferraz Gonçalves 2016a {published data only}
    1. Ferraz Gonçalves JA, Almeida A, Costa I, Silva P, Carneiro R. Comparison of haloperidol alone and in combination with midazolam for the treatment of acute agitation in an Inpatient palliative care service. Journal of Pain & Palliative Care Pharmacotherapy 2016;30(4):284‐8. - PubMed
Grover 2011 {published data only}
    1. Grover S, Kumar V, Chakrabarti S. Comparative efficacy study of haloperidol, olanzapine and risperidone in delirium. Journal of Psychosomatic Research 2011;71(4):277‐81. - PubMed
Han 2004 {published data only}
    1. Han CS, Kim YK. A double‐blind trial of risperidone and haloperidol for the treatment of delirium. Psychosomatics 2004;45(4):297‐301. - PubMed
Han 2010 {published data only}
    1. Han C, Yoon HK, Ko YH. Paliperidone for the treatment of hyperactive delirium: short‐term, open‐label trial. European Neuropsychopharmacology 2010;20:S464‐5.
Hu 2006 {published data only}
    1. Hu H, Deng W, Yang H, Liu Y. Olanzapine and haloperidol for senile delirium: a randomized controlled observation. Chinese Journal of Clinical Rehabilitation 2006;10(42):188‐90.
Kim 2010 {published data only}
    1. Kim SW, Yoo JA, Lee SY, Kim SY, Bae KY, Yan SJ, et al. Risperidone versus olanzapine for the treatment of delirium. Human Psychopharmacology: Clinical and Experimental 2010;25(4):298‐302. - PubMed
Kim 2014 {published data only}
    1. Kim JL, Lee M, Kim TS, Ahn SH. Open‐labeled comparative study of atypical antipsychotics for delirium in elderly patients. Alzheimer's and Dementia 2014;10:P858.
Lee 2005 {published data only}
    1. Lee KU, Won WY, Lee HK, Kweon YS, Lee CT, Pae CU, et al. Amisulpride versus quetiapine for the treatment of delirium: a randomized, open prospective study. International Clinical Psychopharmacology 2005;20(6):311‐4. - PubMed
Lee 2007 {published data only}
    1. Lee CS, Rim GM, Hahn KH, Kim BJ. Comparison of efficacy between aripiprazole and haloperidol in the treatment of patients with delirium. Korean Journal of Psychopharmacology 2007;18(4):240‐5.
Lee 2013 {published data only}
    1. Lee SH, Park SJ. Comparison of efficacy and side effects between aripiprazole and haloperidol in the treatment of delirium. International Psychogeriatrics 2013;25:S132‐3.
Mittal 2004 {published data only}
    1. Mittal D, Jimerson NA, Neely EP, Johnson WD, Kennedy RE, Torres RA, et al. Risperidone in the treatment of delirium: results from a prospective open‐label trial. Journal of Clinical Psychiatry 2004;65(5):662‐7. - PubMed
Miyaji 2007 {published data only}
    1. Miyaji S, Yamamoto K, Hoshino S, Yamamoto H, Sakai Y, Miyaoka H. Comparison of the risk of adverse events between risperidone and haloperidol in delirium patients. Psychiatry and Clinical Neurosciences 2007;61(3):275‐82. - PubMed
Moretti 2004 {published data only}
    1. Moretti R, Torre P, Antonello RM, Cattaruzza T, Cazzato G. Cholinesterase inhibition as a possible therapy for delirium in vascular dementia: a controlled, open 24‐month study of 246 patients. American Journal of Alzheimer's Disease and Other Dementias 2004;19(6):333‐9. - PMC - PubMed
Naber 2007 {published data only}
    1. Naber D, Greenspan A, Schreiner A. Efficacy and safety of risperidone in the treatment of elderly patients suffering from organic brain disease (organic brain syndrome): results from a double‐blind, randomized, placebo‐controlled clinical trail. Psychopharmacology 2007;191(4):1027‐9. - PubMed
Overshott 2010 {published data only}
    1. Overshott R, Vernon M, Morris J, Burns A, Overshott R, Vernon M, et al. Rivastigmine in the treatment of delirium in older people: a pilot study. International Psychogeriatrics / IPA 2010;22(5):812‐8. - PubMed
Parellada 2004 {published data only}
    1. Parellada E, Baeza I, Pablo J, Martinez G. Risperidone in the treatment of patients with delirium. Journal of Clinical Psychiatry 2004;65(3):348‐53. - PubMed
Pelosi 2008 {published data only}
    1. Pelosi A. Donepezil is no more effective than placebo for agitation in people with Alzheimer's disease. Evidence‐based Mental Health 2008;11(3):84. - PubMed
Perkisas 2015 {published data only}
    1. Perkisas SM, Vandewoude MF. Ramelteon for prevention of delirium in hospitalized older patients. JAMA 2015;313(17):1745‐6. - PubMed
Sakong 2010 {published data only}
    1. Sakong JK, Jung SW, Kim JS, Koo BH. Comparison between effectiveness of aripiprazole and risperidone for treatment of delirium in hospitalized patients. European Neuropsychopharmacology 2010;20:S568‐9.
Sasaki 2003 {published data only}
    1. Sasaki Y, Matsuyama T, Inoue S, Sunami T, Inoue T, Denda K, et al. A prospective, open‐label, flexible‐dose study of quetiapine in the treatment of delirium. Journal of Clinical Psychiatry 2003;64(11):1316‐21. - PubMed
Sipahimalani 1998 {published data only}
    1. Sipahimalani A, Masand PS. Olanzapine in the treatment of delirium. Psychosomatics 1998;39(5):422‐30. - PubMed
Tahir 2009 {published data only}
    1. Tahir T. Quetiapine versus placebo in the treatment of delirium: A randomized controlled trial. European Neuropsychopharmacology 2009;19:S358.
Tahir 2010 {published data only}
    1. Tahir TA, Eeles E, Karapareddy V, Muthuvelu P, Chapple S, Phillips B, et al. A randomized controlled trial of quetiapine versus placebo in the treatment of delirium. Journal of Psychosomatic Research 2010;69(5):485‐90. - PubMed
Tanimukai 2016 {published data only}
    1. Tanimukai H, Tsujimoto H, Matsuda Y, Tokoro A, Kanemura S, Watanabe M, et al. Novel Therapeutic Strategies for Delirium in Patients With Cancer: A Preliminary Study. Americal Journal of Hospice and Palliative Care 2016;33(5):456‐62. - PubMed
van der Vorst 2018 {published data only}
    1. Vorst M, Eefjes E, Boddaert Manon, Verdegaal B, Beeker A, Teunissen S, Beekman A, Wilschut J, Berkhof J, Verheul Henk. Efficacy and side effect profile of olanzapine versus haloperidol for symptoms of delirium in hospitalised patients with advanced cancer:a multicenter, investigator‐blinded, randomized, controlled trial. 10th World Research Congress of the European Association for Palliative Care (EAPC). 2018; Vol. 32 (IS):8. [DOI: 10.1177/0269216318769196] - DOI
van Eijk 2010 {published data only}
    1. Eijk MM, Roes KC, Honing ML, Kuiper MA, Karakus A, Jagt M, et al. Effect of rivastigmine as an adjunct to usual care with haloperidol on duration of delirium and mortality in critically ill patients: a multicentre, double‐blind, placebo‐controlled randomised trial. Lancet 2010;376 North American Edition(9755):1829‐37. - PubMed
Yang 2012 {published data only}
    1. Jaewon Y, Wonseok C, Young‐Hoon K, Sook‐Haeng J, Changsu H, Yong‐Ku K. Bright light therapy as an adjunctive treatment with risperidone in patients with delirium: a randomized, open, parallel group study. General Hospital Psychiatry 2012;34(5):546‐51. - PubMed
Yoon 2013 {published data only}
    1. Hyung‐Jun Y, Kyoung‐Min P, Won‐Jung C, Soo‐Hee C, Jin‐Young P, Jae‐Jin K, et al. Efficacy and safety of haloperidol versus atypical antipsychotic medications in the treatment of delirium. BMC Psychiatry 2013;13:240. - PMC - PubMed
Zaslavsky 2012 {published data only}
    1. Zaslavsky A, Haile M, Kline R, Iospa A, Frempong‐Boadu A, Bekker A. Rivastigmine in the treatment of postoperative delirium: a pilot clinical trial. International Journal of Geriatric Psychiatry 2012;27(9):986‐8. - PubMed

References to studies awaiting assessment

van der Vorst 2019 {published data only}
    1. Verheul HMW. Early recognition and optimal treatment of delirium in patients with advanced cancer. ClinicalTrials.gov/ct2/show/NCT01539733 2009.
    1. Vorst MJ, Neefies EC, Boddaert MS, Verdegaal BA, Beeker A, Teunissen SC, et al. Olanzapine versus haloperidol for treatment of delirium in patients with advanced cancer: a phase III randomized clinical trial. Oncologist 2019 Dec 4 [Epub ahead of print]. [DOI: 10.1634/theoncologist.2019-0470] - DOI - PMC - PubMed

References to ongoing studies

NCT03021486 {published data only}
    1. Haloperidol and/or chlorpromazine for refractory agitated delirium. Ongoing study 5 June 2017Estimated study completion date: June 2021.
NCT03743649 {published data only}
    1. Haloperidol and lorazepam in controlling symptoms of persistent agitated delirium in patients with advanced cancer undergoing palliative care. Ongoing study 31 May 2019.

Additional references

Battaglia 2005
    1. Battaglia J. Pharmacological management of acute agitation. Drugs 2005;65(9):1207. - PubMed
Beller 2015
    1. Beller EM, Driel ML, Mcgregor L, Truong S, Mitchell G. Palliative pharmacological sedation for terminally ill adults. Cochrane Database of Systematic Reviews 2015, Issue 1. [DOI: 10.1002/14651858.CD010206] - DOI - PMC - PubMed
Blazer 2019
    1. Blazer Dan G. Pharmacologic Intervention for the treatment and prevention of delirium: looking beneath the modeling. JAMA psychiatry 2019;76(5):472‐3. [DOI: 10.1001/jamapsychiatry.2018.4276] - DOI - PubMed
Breitbart 1997
    1. Breitbart W, Rosenfeld B, Roth A, Smith MJ, Cohen K, Passik S. The Memorial Delirium Assessment Scale. Journal of Pain and Symptom Management 1997;13(3):128‐37. - PubMed
Breitbart 2000
    1. Breitbart W, Strout D. Delirium in the terminally ill. Clinics in Geriatric Medicine 2000;16(2):357‐72. - PubMed
Burry 2018
    1. Burry L, Mehta S, Perreault MM, Luxenberg JS, Siddiqi N, Hutton B, et al. Antipsychotics for treatment of delirium in hospitalised non‐ICU patients. Cochrane Database of Systematic Reviews 2018, Issue 6. [DOI: 10.1002/14651858.CD005594] - DOI - PMC - PubMed
Bush 2014
    1. Bush SH, Kanji S, Pereira JL, Davis DHJ, Currow DC, Meagher D, et al. Treating an established episode of delirium in palliative care: expert opinion and review of the current evidence base with recommendations for future development. Journal of Pain and Symptom Management 2014; Vol. 48, issue 2:231‐48. [DOI: 10.1016/j.jpainsymman.2013.07.018] - DOI - PMC - PubMed
Bush 2017
    1. Bush SH, Tierney S, Lawlor P. Clinical assessment and management of delirium in the palliative care setting. Drugs 2017;77(15):1623‐43. - PMC - PubMed
Bush 2018
    1. Bush SH, Lawlor PG, Ryan K, Centeno C, Lucchesi M, Kanji S, et al. Delirium in adult cancer patients: ESMO Clinical Practice Guidelines. Annals of Oncology 2018;29(Suppl 4):iv143‐iv165. [DOI: 10.1093/annonc/mdy147] - DOI - PubMed
Caraceni 2009
    1. Caraceni A, Simonetti F. Palliating delirium in patients with cancer. Lancet Oncology 2009;10(2):164‐72. [DOI: 10.1016/S1470-2045(09)70018-X] - DOI - PubMed
CCSMH 2010
    1. Canadian Coalition for Seniors’ Mental Health (CCSMH). Guideline on the assessment and treatment of delirium in older adults at the end of life. ccsmh.ca/wp‐content/uploads/2016/03/NatlGuideline_DeliriumEOLC.pdf (accessed 16 January 2020).
CCSMH 2014
    1. Canadian Coalition for Seniors’ Mental Health (CCSMH). 2014 CCSMH Guideline Update: The assessment and treatment of delirium. ccsmh.ca/wp‐content/uploads/2016/03/2014‐ccsmh‐Guideline‐Update‐Delirium... (accessed 16 January 2020).
Cerveira 2017
    1. Cerveira CC, Pupo CC, Sousa Dos Santos S, Mourao Santos JE. Delirium in the elderly: a systematic review of pharmacological and non‐pharmacological treatments. Dementia & Neuropsychologia 2017;11(3):275‐0. - PMC - PubMed
Cherny 2014
    1. Cherny NI. ESMO clinical practice guidelines for the management of refractory symptoms at the end of life and the use of palliative sedation. Annals of Oncology 2014;25(suppl3):iii143‐52. - PubMed
Cipriani 2013
    1. Cipriani Andrea, Higgins Julian PT, Geddes John R, Salanti Georgia. Conceptual and technical challenges in network meta‐analysis. Annals of Internal Medicine 2013;159(2):130. - PubMed
Clegg 2011
    1. Clegg A, Young JB. Which medications to avoid in people at risk of delirium: a systematic review. Age and Ageing 2011;40(1):23‐9. - PubMed
Cochrane 2014
    1. Cochrane PaPaS Group: Data collection forms for intervention reviews. training.cochrane.org/resource/data‐collection‐forms‐intervention‐reviews (accessed 1 March 2017).
Cotton 2011
    1. Cotton D, Taichman D, Williams S, Marcatonio ER. Delirium. Annals of Internal Medicine 2011;154:ITC1‐6.
de Stoutz 1995
    1. Stoutz ND, Tapper M, Fainsinger RL. Reversible delirium in terminally ill patients. Journal of Pain and Symptom Management 1995;10(3):249‐53. - PubMed
Deschartres 2013
    1. Dechartres A, Trinquart L, Boutron I, Ravaud P. Influence of trial sample size on treatment effect estimates: meta epidemiological study. BMJ 2013;346:f2304. [DOI: ] - PMC - PubMed
DSM‐5
    1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. Fifth. American Psychiatric Association, 2013.
EPOC 2015
    1. Effective Practice, Organisation of Care (EPOC). 23. Worksheets for preparing a Summary of Findings using GRADE. Resources for review authors. Available at: epoc.cochrane.org/epoc‐specific‐resources‐review‐authors (accessed 30 July 2018).
Etkind 2017
    1. Etkind SN, Bone AE, Gomes B, Lovell N, Evans CJ, Higginson IJ, et al. How many people will need palliative care in 2040? Past trends, future projections and implications for services. BMC Medicine 2017;15(1):102. - PMC - PubMed
Ferraz Gonçalves 2016b
    1. Ferraz Gonçalves JA, Almeida A, Pereira S. A protocol for the control of agitation in palliative care. American Journal of Hospice and Palliative Medicine 2016;33(10):948‐51. [DOI: 10.1177/1049909115598929] - DOI - PubMed
Finucane 2017
    1. Finucane AM, Lugton J, Kennedy C, Spiller J. The experiences of caregivers of patients with delirium and their role in its management in palliative care settings: an integrative literature review. Psycho‐oncology 2017;26(3):291‐300. [DOI: 10.1002/pon.4140.] - DOI - PMC - PubMed
Fitzgerald 2017
    1. Fitzgerald JM. Delirium clinical motor subtypes: a narrative review of the literature and insights from neurobiology. Aging & Mental Health 2017;22(4):431‐43. [DOI: 10.1080/13607863.2017.1310802] - DOI - PubMed
Ganzini 2008
    1. Ganzini L. Care of patients with delirium at the end of life. Annals of Long‐term Care 2007;15(3):35‐40.
Gaudreau 2005
    1. Gaudreau JD, Gagnon P, Harel F, Tremblay A, Roy MA. Fast, systematic, and continuous delirium assessment in hospitalized patients: the Nursing Delirium Screening Scale. Journal of Pain and Symptom Management 2005;29(4):368‐75. - PubMed
Grande 2000
    1. Grande GE, Todd CJ. Why are trials in palliative care so difficult?. Palliative Medicine 2000;14(1):69‐74. - PubMed
Grassi 2015
    1. Grassi L, Caraceni A, Mitchell AJ, Nanni MG, Berardi MA, Caruso R, et al. Management of delirium in palliative care: a review. Current Psychiatry Reports 2015;17(13):1‐9. [DOI: 10.1007/s11920-015-0550-8] - DOI - PubMed
Guyatt 2011
    1. Guyatt GH, Oxman AD, Kunz R, Woodcock J, Brozek J, Helfand M, et al. GRADE guidelines: 7. Rating the quality of evidence‐inconsistency. Journal of Cinical Epidemiology 2011;64(12):1294–302. [DOI: 10.1016/j.jclinepi.2011.03.017] - DOI - PubMed
Guyatt 2013a
    1. Guyatt G, Oxman AD, Sultan S, Brozek J, Glasziou P, Alonso‐Coello P, et al. GRADE guidelines: 11. Making an overall rating of confidence in effect estimates for a single outcome and for all outcomes. Journal of Clinical Epidemiology 2013;66:151–7. [DOI: 10.1016/j.jclinepi.2012.01.006] - DOI - PubMed
Guyatt 2013b
    1. Guyatt GH, Oxman AD, Santesso N, Helfand M, Vist G, Kunz R, et al. GRADE guidelines: 12. Preparing summary of findings tables‐binary outcomes. Journal of Clinical Epidemiology 2013;66:158–72. [DOI: 10.1016/j.jclinepi.2012.01.012] - DOI - PubMed
Hatta 2014
    1. Hatta K, Kishi Y, Wada K, Odawara T, Takeuchi T, Takafumi S, et al. Antipsychotics for delirium in the general hospital setting in consecutive 2453 inpatients: a prospective observational study. International Journal of Geriatric Psychiatry 2014; Vol. 29, issue 3:253‐62. [DOI: 10.1002/gps.3999] - DOI - PMC - PubMed
Higgins 2011
    1. Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from handbook.cochrane.org.
Hosie 2012
    1. Hosie A, Davidson PM, Agar M, Sanderson CR, Phillips J. Delirium prevalence, incidence, and implications for screening in specialist palliative care inpatient settings: a systematic review. Palliative Medicine 2012;27(6):486‐98. [DOI: 10.1177/0269216312457214] - DOI - PubMed
Hosker 2016
    1. Hosker MG, Bennet MI. Delirium and agitation at the end of life. BMJ 2016;353:i3085. [DOI: 10.1136/bmj.i3085] - DOI - PubMed
Ingham 1998
    1. Ingham JM, Caraceni AT. Delirium. In: Berger AM, Portenoy RK, Weissman DE editor(s). Principles and Practices of Supportive Oncology. Philadelphia, PA: Lippincott‐Raven, 1998:477‐96.
Inouye 2001
    1. Inouye SK, Foreman MD, Mion LC, Katz KH, Cooney Jr LM. Nurses' recognition of delirium and its symptoms: comparison of nurse and researcher ratings. Archives of Internal Medicine 2001;161(20):2467‐73. [DOI: ] - PubMed
Inouye 2003
    1. Inouye SK, Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying confusion: the confusion assessment method. A new method for detection of delirium. Annals of Internal Medicine 1990;113(12):941‐8. - PubMed
Inouye 2006
    1. Inouye SK. Delirium in older persons. New England Journal of Medicine 2006;354(11):1157‐65. - PubMed
Inouye 2014
    1. Inouye SK, Westendorp R, Saczynski JS. Delirium in elderly people. Lancet 2014;383(9920):911‐22. - PMC - PubMed
Irwin 2013
    1. Irwin SA, Pirrello RD, Hirst JM, Buckholz GT, Ferris FD. Clarifying delirium management: practical, evidenced‐based, expert recommendations for clinical practice. Journal of Palliative Medicine 2013;16(4):423‐35. - PMC - PubMed
Jackson 1999
    1. Jackson KC, Lipman AG. Delirium in palliative care patients. Journal of Pharmaceutical Care in Pain & Symptom Control 1999;7:59‐70.
Kishi 2016
    1. Kishi T, Hirota T, Matsunaga S, Iwata N. Antipsychotic medications for the treatment of delirium: a systematic review and meta‐analysis of randomised controlled trials. Journal of Neurology, Neurosurgery, and Psychiatry 2016;87(7):767. - PubMed
Lawley 2017
    1. Lawley H, Hewison A. An integrative literature review exploring the clinical management of delirium in patients with advanced cancer. Journal of Clinical Nursing 2017;26(23‐24):4172‐83. - PubMed
Lawlor 2000
    1. Lawlor PG, Gagnon B, Mancini IL, Pereira JL, Hanson J, Suarez‐Almazor ME, et al. Occurrence, causes, and outcome of delirium in patients with advanced cancer: a prospective study. Archives of Internal Medicine 2000;160(6):786‐94. [DOI: 10.1001/jama.284.19.2427] - DOI - PubMed
Leonard 2008
    1. Leonard M, Raju B, Conroy M, Donnelly S, Trzepacz Pt, Saunders J, et al. Reversibility of delirium in terminally ill patients and predictors of mortality. Palliative Medicine 2008;22(7):848‐54. - PubMed
Leonard 2014
    1. Leonard MM, Nekolaichuk C, Meagher DJ, Barnes C, Gaudreau JD, Watanabe S, et al. Practical assessment of delirium in palliative care. Journal of Pain and Symptom Management 2014;48(2):176‐90. [DOI: 10.1016/j.jpainsymman.2013.10.024] - DOI - PubMed
Lo 2005
    1. Lo B, Rubenfeld G. Palliative sedation in dying patients: "we turn to it when everything else hasn't worked". JAMA 2005;294(14):1810‐6. - PubMed
Lowe 2016
    1. Lowe EM, Elliot V, Owen R, Adams C, Shiels RE. How do UK palliative care physicians manage delirium? Results of an online survey. European Journal of Palliative Care 2016;23(3):110‐3.
Maltoni 2012
    1. Maltoni M, Scarpi E, Rosati M, Derni S, Fabbri L, Martini F, et al. Palliative sedation in end‐of‐life care and survival: a systematic review. Journal of Clinical Oncology 2012;30(12):1378. - PubMed
Meagher 2008
    1. Meagher D, Moran M, Bangaru R, Leonard M, Donnelly S, Saunders J, et al. A new data‐based motor subtype schema for delirium. Journal of Neuropsychiatry and Clinical Neurosciences 2008;20(2):185‐93. [DOI: 10.1176/jnp.2008.20.2.185] - DOI - PubMed
Meagher 2012
    1. Meagher DJ, Leonard M, Donnelly S, Conroy M, Adamis D, Trzepacz PT. A longitudinal study of motor subtypes in delirium: relationship with other phenomenology, etiology, medication exposure and prognosis. Journal of Psychosomatic Research 2012;71:395‐403. [DOI: 10.1016/j.jpsychores.2011.06.001] - DOI - PubMed
Meagher 2017
    1. Meagher D, Agar M, Teodorczuk A. Debate article: antipsychotic medications are clinically useful for the treatment of delirium. International Journal of Geriatric Psychiatry 2017;Nov 33(11):1420‐1427. - PubMed
Middlemiss 2015
    1. Middlemiss T, Lloyd‐Williams M, Laird BJ, Fallon MT. Symptom control trials in patients with advanced cancer: a qualitative study. Journal of Pain and Symptom Management 2015;50(5):642–9.e1. - PMC - PubMed
Moher 2009
    1. Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta‐analyses: the PRISMA statement. Annals of Internal Medicine 2009;151(4):264. - PubMed
Morandi 2013
    1. Morandi A, Davis D, Taylor JK, Bellelli G, Olofsson B, Kreisel S, et al. Consensus and variations in opinions on delirium care: a survey of European delirium specialists. International Psychogeriatrics 2013;25(12):2067‐75. - PMC - PubMed
Moyer 2011
    1. Moyer DD. Terminal delirium in geriatric patients with cancer at end of life. American Journal of Hospice & Palliative Care 2011;28(1):44‐51. - PubMed
Neufeld 2016
    1. Neufeld KJ, Yue J, Robinson TN, Inouye SK, Needham DM. Antipsychotic medication for prevention and treatment of delirium in hospitalized adults: a systematic review and meta‐analysis. Journal of the American Geriatrics Society 2016;64(4):714‐5. - PMC - PubMed
NHS Scotland 2014
    1. Scottish Palliative Care Guidelines 2014. www.palliativecareguidelines.scot.nhs.uk (accessed 1 March 2018).
NICE 2010
    1. NICE. Delirium: diagnosis, prevention and management. [CG103] London: National Institute for Health and Clinical Excellence (NICE). London: National Institute for Health and Clinical Excellence (NICE), 2010.
NICE 2015
    1. National Institute for Health and Care Excellence. Care of dying adults in the last days of life. Clinical Guideline NG31 16 December 2015:nice.org.uk/guidance/ng31 Accessed on 1 September 2018. - PubMed
O'Malley 2008
    1. O'Malley G, Leonard M, Meagher D, O'Keeffe S. The delirium experience: a review. Journal of Psychosomatic Research 2008;65(3):223‐8. [DOI: 10.1016/j.jpsychores.2008.05.017] - DOI - PubMed
Partridge 2013
    1. Partridge JSI, Martin FC, Harari D, Dhesi JK. The delirium experience: what is the effect on patients, relatives and staff and what can be done to modify this?. International Journal of Geriatric Psychiatry 2013; Vol. 28, issue 8:804‐12. [DOI: 10.1002/gps.3900] - PubMed
Review Manager 2014 [Computer program]
    1. Nordic Cochrane Centre. Review Manager 5 (RevMan 5). Version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014.
Rockwood 2008
    1. Rockwood K. Causes of delirium. Psychiatry 2008;7(1):39‐41. [DOI: 10.1016/j.mppsy.2007.11.003] - DOI
Roth 1996
    1. Roth AJ, Breitbart W. Psychiatric emergencies in terminally ill cancer patients. Hematology/oncology Clinics of North America 1996;10(1):235‐59. - PubMed
Sanchez‐Roman 2014
    1. Sanchez‐Roman S, Zavala CB, Solares AL, Chiquete E. Delirium in adult patients receiving palliative care: a systematic review of the literature. Revista de Psiquiatria y Salud Mental (English Edition) 2014;7(1):48. - PubMed
Schünemann 2017
    1. Schünemann HJ, Oxman AD, Higgins JPT, Vist GE, Glasziou P, Akl E, Guyatt GH on behalf of the Cochrane GRADEing Methods Group and the Cochrane Statistical Methods Group. Chapter 11: Completing ‘Summary of findings’ tables and grading the confidence in or quality of the evidence. In: Higgins JP, Churchill R, Chandler J, Cumpston MS, editor(s), Cochrane Handbook for Systematic Reviews of Interventions version 5.2.0 (updated June 2017). The Cochrane Collaboration, 2017. Available from www.training.cochrane.org/handbook.
SIGN 2019
    1. Risk reduction and management of delirium: A national clinical guideline. www.sign.ac.uk/assets/sign157.pdf (accessed 13 March 2019).
Spiller 2006
    1. Spiller JA, Keen JC. Hypoactive delirium: assessing the extent of the problem for inpatient specialist palliative care. Palliative Medicine 2006;20(1):17‐23. - PubMed
Sweet 2014
    1. Sweet L, Adamis D, Meagher DJ, Davis D, Currow DC, Bush SH, et al. Ethical challenges and solutions regarding delirium studies in palliative care. Journal of Pain and Symptom Management 2014;48(2):271‐59. - PMC - PubMed
Trzepacz 1988
    1. Trzepacz PT, Baker RW, Greenhouse J. A symptom rating scale for delirium. Psychiatry Research 1988;23(1):89‐97. - PubMed
Twycross 2017
    1. Twycross R, Wilcock A, Howard P. Palliative Care Formulary. Sixth. London: Pharmaceutical Press, 2017.
Wang 2013
    1. Wang HR, Woo YS, Bahk WM. Atypical antipsychotics in the treatment of delirium. Psychiatry and Clinical Neurosciences 2013; Vol. 67, issue 5:323‐31. - PubMed
Watt 2019
    1. Watt CL, Momoli F, Ansari MT, Sikora L, Bush SH, Hosie A, et al. The incidence and prevalence of delirium across palliative care settings: a systematic review. Palliative Medicine 2019;33(8):865‐77. - PMC - PubMed
WHO 2018
    1. WHO. WHO Definition of palliative care. www.who.int/cancer/palliative/definition/en (accessed 1 March 2018).
Wu 2019
    1. Wu YC, Tseng PT, Tu YK, Hsu CY, Liang CS, Yeh TC, et al. Association of delirium response and safety of pharmacological interventions for the management and prevention of delirium: a network meta‐analysis. JAMA Psychiatry 2019; Vol. 76, issue 5:526‐35. [DOI: 10.1001/jamapsychiatry.2018.4365] - DOI - PMC - PubMed
Zaal 2015
    1. Zaal I, Devlin J, Hazelbag M, Klein PK, Kooi A, Ong D, et al. Benzodiazepine‐associated delirium in critically ill adults. Intensive Care Medicine 2015;41(12):2137‐40. - PubMed
Zhang 2013
    1. Zhang Z, Xu X, Ni H. Small studies may over estimate the effect sizes in critical care meta‐analyses: a meta epidemiological study. Critical Care (London, England) 2013;17(1):R2. [DOI: 10.1186/cc11919] - DOI - PMC - PubMed

References to other published versions of this review

Candy 2012
    1. Candy B, Jackson KC, Jones L, Leurent B, Tookman A, King M. Drug therapy for delirium in terminally ill adult patients. Cochrane Database of Systematic Reviews 2012, Issue 2. [DOI: 10.1002/14651858.CD004770.pub2] - DOI - PubMed
Jackson 2004
    1. Jackson KC, Lipman AG. Drug therapy for delirium in terminally ill adult patients. Cochrane Database of Systematic Reviews 2004, Issue 2. [DOI: 10.1002/14651858.CD004770] - DOI - PubMed