Antipsychotics Worsen Symptoms in Patients with Delirium Who Receive Palliative Care


Am Fam Physician. 2017 Mar 15;95(6):online.

Clinical Question

Do antipsychotic drugs improve symptoms of distress associated with delirium in patients receiving palliative care?

Bottom Line

For hospitalized patients with acute delirium and symptoms of distress who are receiving palliative care, the use of risperidone (Risperdal) or haloperidol at conservative oral doses worsens symptoms and may shorten overall survival. (Level of Evidence = 1b)


These researchers enrolled 247 hospitalized patients who were receiving palliative care and had delirium-related symptoms of distress. Patients were randomized, using concealed allocation, to receive oral risperidone, haloperidol, or placebo for 72 hours for the management of these symptoms. There were slightly more than 80 patients in each of the three arms. The initial dosage for risperidone and haloperidol was 1 mg, with maintenance dosages of 0.5 mg every 12 hours titrated to a maximum dosage of 4 mg per day. Patients older than 65 years received half this dosage. All patients also received nonpharmacologic measures for delirium treatment, such as vision and/or hearing aids and frequent reorientation, as well as treatment for reversible precipitants of delirium. Subcutaneous midazolam was given as needed for patients who required immediate intervention for safety or distress.

Delirium symptom scores were obtained every eight hours using the three items on the Nursing Delirium Screening Scale that are considered measures of distress (inappropriate behavior, inappropriate communication, and illusions/hallucinations). Each item was scored from 0 to 2, based on the presence and intensity of the symptom, for a total score of 0 to 6. The primary outcome was the average of the last two delirium symptom scores on day 3 of treatment. The three study groups had similar delirium symptom scores at baseline. The mean age in each group was 75 years, and almost 90% of patients had cancer. Analysis was by intention to treat.

Overall, patients who received haloperidol and patients who received risperidone had significantly higher delirium symptom scores at day 3, compared with those who received placebo, by an average of 0.48 and 0.24, respectively. Both intervention groups also required more rescue midazolam than did the placebo group. Finally, the haloperidol group was noted to have decreased overall survival compared with the placebo group (hazard ratio = 1.73; 95% confidence interval, 1.20 to 2.50; P = .003). The authors suggest that this may be due to prolonged delirium or longer exposure to antipsychotics. Survival was also decreased in the risperidone group, although this did not reach statistical significance.

Study design: Randomized controlled trial (double-blinded)

Funding source: Government

Allocation: Concealed

Setting: Inpatient (ward only)

Reference: Agar MR, Lawlor PG, Quinn S, et al. Efficacy of oral risperidone, haloperidol, or placebo for symptoms of delirium among patients in palliative care: a randomized clinical trial. JAMA Intern Med. 2017;177(1):34–42.

POEMs (patient-oriented evidence that matters) are provided by EssentialEvidence Plus, a point-of-care clinical decision support system published by Wiley-Blackwell. For more information, please see http://www.essentialevidenceplus.com. Copyright Wiley-Blackwell. Used with permission.

For definitions of levels of evidence used in POEMs, see http://www.essentialevidenceplus.com/product/ebm_loe.cfm?show=oxford.

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This series is coordinated by Sumi Sexton, MD, Associate Deputy Editor.

A collection of POEMs published in AFP is available at https://www.aafp.org/afp/poems.



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