By Martin Lipsky, MD

Chancellor, South Jordan Campus, Roseman University of Health Sciences, South Jordan, UT

Dr. Lipsky reports no financial relationships relevant to this field of study.

SYNOPSIS: In palliative care patients suffering from delirium, managing delirium precipitants and individualized supportive strategies alone work better than adding risperidone or haloperidol.

SOURCE: 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;177:34-42.

Patients in palliative care commonly experience delirium. Symptom relief is important for these patients. Crafting evidence-based strategies to address delirium optimally is crucial. Management strategies include both pharmacologic and non-pharmacologic methods. Antipsychotics remain one of the most commonly used pharmacologic treatments, yet the risks associated with their use1 make it essential to evaluate their benefits. Agar et al2 set out to determine if risperidone or haloperidol, administered in addition to non-pharmacologic care, provided additional benefit in reducing symptoms of delirium when compared to placebo.

The study was a double-blind, parallel-arm, dose-titrated, randomized, clinical trial conducted at 11 Australian inpatient hospice or hospital palliative care services. The study consisted of 247 participants with a mean age of 74.9 years who exhibited a life-limiting illness, delirium, and a delirium score (sum of Nursing Delirium Screen Scale behavioral, communication, and perceptual items) of 1 or more. Among the study group, 85 were women and 218 patients had cancer, making it the most common diagnosis. In the intention-to-treat analysis, 82 received risperidone, 81 received haloperidol, and 84 received placebo. Participants in the risperidone arm demonstrated significantly higher delirium scores compared to placebo (on average 0.24 units higher, 95% confidence interval [CI], 0.06-0.42; P = 0.009). The authors discovered similarly significant differences in the haloperidol arm. Both treatment arms experienced significantly more extrapyramidal effect, and dropout rates for the risperidone group (31 of 82 patients) were about twice the rates of haloperidol (18 of 81 patients) and placebo (15 of 84 patients). Overall survival rate in the placebo group was better than for both the risperidone and haloperidol groups, but only the difference for those receiving haloperidol (hazard ratio, 1.73; 95% CI, 1.20-2.50; P = 0.03) achieved statistical significance. (Placebo vs. risperidone arm hazard ratio, 1.29; 95% CI, 0.91-1.84; P = 0.14).

The authors concluded that for palliative care patients presenting with delirium, management of delirium precipitants and supportive strategies alone result in lower delirium scores and shorter duration of symptoms than when adding either risperidone or haloperidol.

COMMENTARY

Antipsychotics are used commonly to alleviate the troubling behavioral symptoms associated with delirium. Despite the wide use of antipsychotics to help control behavioral symptoms, Agar et al found that not only may antipsychotics provide no benefit, risperidone and haloperidol seem to increase the intensity and duration of symptoms. Less surprising was that haloperidol use decreased overall survival. Other studies also demonstrated the dangers of antipsychotic drugs in the elderly and indicated that older patients presenting with dementia treated with atypical antipsychotics experienced about twice the mortality rate of those taking placebo.3

Although the first-line treatment for delirium is avoiding precipitating factors and instituting non-pharmacologic measures, antipsychotics are used commonly for uncontrolled symptoms because of their perceived effectiveness. These findings, demonstrating that those taking either risperidol or haloperidol experience less symptom relief and worsened survival, suggest that these agents should not be used to treat elderly patients suffering from delirium. The authors noted one study limitation was that few participants were younger than 65 years of age, and perhaps these drugs might demonstrate less risk and greater utility in younger patients. It is also possible that other drugs in this class may be more effective. However, even though the authors highlighted the need for further study, at this point this study suggests that antipsychotics exhibit little or no treatment role for patients in palliative care with symptoms of delirium.

REFERENCES

  1. Winslow BT, Onysko MK, Stob CM, Hazlewood KA. Treatment of Alzheimer disease. Am Fam Physician 2011;83:1403-1412.
  2. 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;177:34-42.
  3. Gill SS, Bronskill SE, Normand SL, et al. Antipsychotic drug use and mortality in older adults with dementia. Ann Intern Med 2007;146:775-786.