Efficacy of Oral Risperidone, Haloperidol, or Placebo for Symptoms of Delirium Among Patients in Palliative Care A Randomized Clinical Trial

Agar, M; Lawlor, P; Quinn, S; Draper, B; Caplan, G; Rowett, D; Sanderson, C; Hardy, J; Le, B; Eckermann, S; McCaffrey, N; Devilee, L; Fazekas, B; Hill, M; Currow, D

Efficacy of Oral Risperidone, Haloperidol, or Placebo for Symptoms of Delirium Among Patients in Palliative Care A Randomized Clinical Trial

Agar, M

Lawlor, P Quinn, S Draper, B Caplan, G Rowett, D Sanderson, C

Hardy, J Le, B

Eckermann, S McCaffrey, N Devilee, L Fazekas, B Hill, M Currow, D

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Publisher:: American Medical Association
Publication Type:: Journal Article
Citation:: JAMA Internal Medicine, 2017, 177, (1), pp. 34-42
Issue Date:: 2017

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Field	Value	Language
dc.contributor.author	Agar, M https://orcid.org/0000-0002-6756-6119
dc.contributor.author	Lawlor, P
dc.contributor.author	Quinn, S
dc.contributor.author	Draper, B
dc.contributor.author	Caplan, G
dc.contributor.author	Rowett, D
dc.contributor.author	Sanderson, C https://orcid.org/0000-0001-5423-5778
dc.contributor.author	Hardy, J
dc.contributor.author	Le, B https://orcid.org/0000-0002-0830-4864
dc.contributor.author	Eckermann, S
dc.contributor.author	McCaffrey, N
dc.contributor.author	Devilee, L
dc.contributor.author	Fazekas, B
dc.contributor.author	Hill, M
dc.contributor.author	Currow, D https://orcid.org/0000-0003-1988-1250
dc.date.accessioned	2022-08-06T21:59:34Z
dc.date.available	2022-08-06T21:59:34Z
dc.date.issued	2017
dc.identifier.citation	JAMA Internal Medicine, 2017, 177, (1), pp. 34-42
dc.identifier.issn	2168-6114
dc.identifier.issn	2168-6106
dc.identifier.uri	http://hdl.handle.net/10453/159716
dc.description.abstract	Importance: Antipsychotics are widely used for distressing symptoms of delirium, but efficacy has not been established in placebo-controlled trials in palliative care. Objective: To determine efficacy of risperidone or haloperidol relative to placebo in relieving target symptoms of delirium associated with distress among patients receiving palliative care. Design, Setting, and Participants: A double-blind, parallel-arm, dose-titrated randomized clinical trial was conducted at 11 Australian inpatient hospice or hospital palliative care services between August 13, 2008, and April 2, 2014, among participants with life-limiting illness, delirium, and a delirium symptoms score (sum of Nursing Delirium Screening Scale behavioral, communication, and perceptual items) of 1 or more. Interventions: Age-adjusted titrated doses of oral risperidone, haloperidol, or placebo solution were administered every 12 hours for 72 hours, based on symptoms of delirium. Patients also received supportive care, individualized treatment of delirium precipitants, and subcutaneous midazolam hydrochloride as required for severe distress or safety. Main Outcome and Measures: Improvement in mean group difference of delirium symptom score (severity range, 0-6) between baseline and day 3. Five a priori secondary outcomes: delirium severity, midazolam use, extrapyramidal effects, sedation, and survival. Results: Two hundred forty-seven participants (mean [SD] age, 74.9 [9.8] years; 85 women [34.4%]; 218 with cancer [88.3%]) were included in intention-to-treat analysis (82 receiving risperidone, 81 receiving haloperidol, and 84 receiving placebo). In the primary intention-to-treat analysis, participants in the risperidone arm had delirium symptom scores that were significantly higher than those among participants in the placebo arm (on average 0.48 Units higher; 95% CI, 0.09-0.86; P = .02) at study end. Similarly, for those in the haloperidol arm, delirium symptom scores were on average 0.24 Units higher (95% CI, 0.06-0.42; P = .009) than in the placebo arm. Compared with placebo, patients in both active arms had more extrapyramidal effects (risperidone, 0.73; 95% CI, 0.09-1.37; P = .03; and haloperidol, 0.79; 95% CI, 0.17-1.41; P = .01). Participants in the placebo group had better overall survival than those receiving haloperidol (hazard ratio, 1.73; 95% CI, 1.20-2.50; P = .003), but this was not significant for placebo vs risperidone (hazard ratio, 1.29; 95% CI, 0.91-1.84; P = .14). Conclusions and Relevance: In patients receiving palliative care, individualized management of delirium precipitants and supportive strategies result in lower scores and shorter duration of target distressing delirium symptoms than when risperidone or haloperidol are added.
dc.format	Print
dc.language	eng
dc.publisher	American Medical Association
dc.relation	http://purl.org/au-research/grants/nhmrc/480476
dc.relation.ispartof	JAMA Internal Medicine
dc.relation.isbasedon	10.1001/jamainternmed.2016.7491
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	1103 Clinical Sciences, 1113 Opthalmology and Optometry, 1117 Public Health and Health Services
dc.subject.mesh	Administration, Oral
dc.subject.mesh	Aged
dc.subject.mesh	Antipsychotic Agents
dc.subject.mesh	Australia
dc.subject.mesh	Delirium
dc.subject.mesh	Double-Blind Method
dc.subject.mesh	Female
dc.subject.mesh	Geriatric Assessment
dc.subject.mesh	Haloperidol
dc.subject.mesh	Humans
dc.subject.mesh	Male
dc.subject.mesh	Palliative Care
dc.subject.mesh	Placebos
dc.subject.mesh	Risperidone
dc.subject.mesh	Treatment Outcome
dc.subject.mesh	Humans
dc.subject.mesh	Delirium
dc.subject.mesh	Haloperidol
dc.subject.mesh	Risperidone
dc.subject.mesh	Antipsychotic Agents
dc.subject.mesh	Placebos
dc.subject.mesh	Treatment Outcome
dc.subject.mesh	Palliative Care
dc.subject.mesh	Administration, Oral
dc.subject.mesh	Geriatric Assessment
dc.subject.mesh	Double-Blind Method
dc.subject.mesh	Aged
dc.subject.mesh	Australia
dc.subject.mesh	Female
dc.subject.mesh	Male
dc.title	Efficacy of Oral Risperidone, Haloperidol, or Placebo for Symptoms of Delirium Among Patients in Palliative Care A Randomized Clinical Trial
dc.type	Journal Article
utslib.citation.volume	177
utslib.location.activity	United States
utslib.for	1103 Clinical Sciences
utslib.for	1117 Public Health and Health Services
utslib.for	1103 Clinical Sciences
utslib.for	1113 Opthalmology and Optometry
utslib.for	1117 Public Health and Health Services
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Health
pubs.organisational-group	/University of Technology Sydney/Faculty of Health/IMPACCT
utslib.copyright.status	closed_access	*
pubs.consider-herdc	true
dc.date.updated	2022-08-06T21:59:33Z
pubs.issue	1
pubs.publication-status	Published
pubs.volume	177
utslib.citation.issue	1

Abstract:

Importance: Antipsychotics are widely used for distressing symptoms of delirium, but efficacy has not been established in placebo-controlled trials in palliative care. Objective: To determine efficacy of risperidone or haloperidol relative to placebo in relieving target symptoms of delirium associated with distress among patients receiving palliative care. Design, Setting, and Participants: A double-blind, parallel-arm, dose-titrated randomized clinical trial was conducted at 11 Australian inpatient hospice or hospital palliative care services between August 13, 2008, and April 2, 2014, among participants with life-limiting illness, delirium, and a delirium symptoms score (sum of Nursing Delirium Screening Scale behavioral, communication, and perceptual items) of 1 or more. Interventions: Age-adjusted titrated doses of oral risperidone, haloperidol, or placebo solution were administered every 12 hours for 72 hours, based on symptoms of delirium. Patients also received supportive care, individualized treatment of delirium precipitants, and subcutaneous midazolam hydrochloride as required for severe distress or safety. Main Outcome and Measures: Improvement in mean group difference of delirium symptom score (severity range, 0-6) between baseline and day 3. Five a priori secondary outcomes: delirium severity, midazolam use, extrapyramidal effects, sedation, and survival. Results: Two hundred forty-seven participants (mean [SD] age, 74.9 [9.8] years; 85 women [34.4%]; 218 with cancer [88.3%]) were included in intention-to-treat analysis (82 receiving risperidone, 81 receiving haloperidol, and 84 receiving placebo). In the primary intention-to-treat analysis, participants in the risperidone arm had delirium symptom scores that were significantly higher than those among participants in the placebo arm (on average 0.48 Units higher; 95% CI, 0.09-0.86; P = .02) at study end. Similarly, for those in the haloperidol arm, delirium symptom scores were on average 0.24 Units higher (95% CI, 0.06-0.42; P = .009) than in the placebo arm. Compared with placebo, patients in both active arms had more extrapyramidal effects (risperidone, 0.73; 95% CI, 0.09-1.37; P = .03; and haloperidol, 0.79; 95% CI, 0.17-1.41; P = .01). Participants in the placebo group had better overall survival than those receiving haloperidol (hazard ratio, 1.73; 95% CI, 1.20-2.50; P = .003), but this was not significant for placebo vs risperidone (hazard ratio, 1.29; 95% CI, 0.91-1.84; P = .14). Conclusions and Relevance: In patients receiving palliative care, individualized management of delirium precipitants and supportive strategies result in lower scores and shorter duration of target distressing delirium symptoms than when risperidone or haloperidol are added.

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http://hdl.handle.net/10453/159716