What is the role of Risperdal (risperidone) in managing combative behavior in hospice patients?

Risperidone for Combative Behavior in Hospice Patients

Risperidone can be used cautiously at very low doses (starting 0.25 mg daily at bedtime, maximum 2-3 mg/day) for severe combativeness in hospice patients, but recent high-quality evidence suggests that supportive care and treatment of underlying delirium causes may be superior, and antipsychotics including risperidone are associated with increased extrapyramidal symptoms and potentially worse survival in palliative care populations. 1, 2

Evidence-Based Approach to Combative Behavior

First-Line Management: Non-Pharmacologic and Supportive Care

• Identify and treat reversible causes of delirium first, including metabolic disturbances, hypoxia, bowel obstruction, infection, CNS events, bladder obstruction, and medication effects (particularly opioids, benzodiazepines, anticholinergics). 1

• The 2017 JAMA Internal Medicine randomized controlled trial (N=247,88% cancer patients) demonstrated that individualized management of delirium precipitants with supportive strategies resulted in lower delirium symptom scores than when risperidone or haloperidol were added. 2

• This landmark study showed risperidone actually worsened delirium symptoms by 0.48 units compared to placebo (95% CI, 0.09-0.86; P=.02), with more extrapyramidal effects (0.73 units higher; P=.03). 2

When Pharmacologic Management Is Necessary

For severe psychomotor agitation, combativeness, or problematic delusions/hallucinations that pose safety risks despite supportive care:

Dosing Protocol for Risperidone

• Start at 0.25 mg daily at bedtime in hospice/palliative care patients, as this population is particularly vulnerable to adverse effects. 1

• Titrate slowly to maximum 2-3 mg/day (usually divided twice daily), with current research supporting use of low dosages. 1

• Extrapyramidal symptoms may occur at doses ≥2 mg/day, so consider dose reduction rather than adding anticholinergic medications if these develop. 1

Critical Safety Considerations

• Haloperidol treatment was associated with significantly poorer overall survival in long-term follow-up (hazard ratio 1.73; 95% CI, 1.20-2.50; P=.003) compared to placebo in the palliative care population. 2

• Risperidone showed a trend toward worse survival (hazard ratio 1.29) though not statistically significant. 2

• In elderly patients with cardiovascular disease, particular caution is advised as adverse events including hypotension (29%), symptomatic orthostasis (10%), and cardiac events have been reported. 3

Alternative Considerations Based on Life Expectancy

For patients with weeks to days of life expectancy (actively dying):

• Haloperidol 0.5-1 mg every 1-4 hours PRN remains a guideline-recommended option for severe delirium with agitation, with alternative agents including risperidone 0.5-1 mg twice daily, olanzapine 2.5-15 mg daily, or quetiapine 50-100 mg twice daily. 1

• If agitation is refractory to high doses of neuroleptics, consider adding lorazepam 0.5-2 mg every 4-6 hours rather than escalating antipsychotic doses. 1

For patients with months of life expectancy:

• Evaluate primary therapy and use haloperidol 0.5-1 mg twice daily or alternative atypical antipsychotics at the doses listed above. 1

• Orient patient with family presence and focus on symptom control while supporting family coping mechanisms. 1

Common Pitfalls to Avoid

• Do not use risperidone as first-line treatment without addressing underlying delirium causes, as the 2017 RCT demonstrated worse outcomes compared to supportive care alone. 2

• Avoid rapid dose escalation, as adverse effects in elderly patients are associated with relatively rapid dose increases. 3

• Do not combine with multiple psychotropic agents unnecessarily, as cotreatment with SRI antidepressants or valproate increases adverse event risk. 3

• Recognize that atypical antipsychotics have diminished but not eliminated risk of extrapyramidal symptoms and tardive dyskinesia compared to typical agents. 1

Clinical Algorithm Summary

1. Assess and treat reversible delirium causes (metabolic, infection, medications, constipation, urinary retention) 1
2. Implement supportive care measures (family presence, orientation, environmental modifications) 1, 2
3. If severe combativeness persists and poses safety risk, consider risperidone 0.25 mg at bedtime 1
4. Titrate slowly over days to effect (maximum 2-3 mg/day divided) 1
5. Monitor closely for extrapyramidal symptoms, hypotension, and sedation 1, 3, 2
6. If refractory agitation, add lorazepam rather than escalating antipsychotic 1