What is the recommended pharmacotherapy approach for delirium?

Pharmacotherapy for Delirium

The recommended pharmacotherapy approach for delirium should focus primarily on treating underlying causes rather than using antipsychotics, as evidence shows haloperidol and risperidone have no demonstrable benefit and may worsen symptoms in mild-to-moderate delirium. 1

First-Line Approach

• Identify and treat reversible precipitating factors, which can lead to resolution in up to 50% of delirium cases 1
• Implement non-pharmacological interventions (reorientation, cognitive stimulation, sleep hygiene) before considering medications 1
• Reduce or eliminate delirium-inducing medications (steroids, anticholinergics) whenever possible 1

Pharmacotherapy Algorithm Based on Delirium Type

For Opioid-Associated Delirium:

• Rotate opioids to fentanyl or methadone, or reduce the current opioid dose by 30-50% 1

For Mild-to-Moderate Delirium:

• Avoid haloperidol and risperidone as they show no benefit and may worsen symptoms 1
• Consider second-generation antipsychotics if symptoms are distressing:
  • Olanzapine 2.5-5 mg PO/SC (available as orally disintegrating tablet or parenteral) 1
  • Quetiapine 25 mg PO (immediate release) 1
  • Aripiprazole 2.5-5 mg PO/SC 1

For Hypoactive Delirium:

• Methylphenidate may improve cognition when no delusions or perceptual disturbances are present and no cause has been identified 1
• Consider psychostimulants (methylphenidate 2.5-5 mg orally with breakfast) for refractory daytime sedation 1

For Severe/Hyperactive Delirium:

• For acute management of severe symptomatic distress, benzodiazepines can provide sedation and anxiolysis 1
• Benzodiazepines should be first-line only for alcohol or benzodiazepine withdrawal delirium 1
• Lorazepam is the preferred benzodiazepine due to its rapid onset, shorter duration, low risk of accumulation, and predictable bioavailability 2

Important Considerations

• Use pharmacological interventions only for patients with distressing symptoms (perceptual disturbances) or safety concerns 1
• Use medications at the lowest effective dose and for the shortest time possible 1
• Monitor for side effects:
  • Second-generation antipsychotics have fewer extrapyramidal side effects than first-generation options 1, 3
  • Sedation from olanzapine and quetiapine may be beneficial in hyperactive delirium 1
  • High-dose haloperidol (>4.5 mg/day) has increased risk of extrapyramidal effects compared to olanzapine 3

Special Populations

• For critically ill patients, use standardized assessment tools like CAM-ICU or ICDSC 1
• For end-of-life care, focus on symptom management and family support if delirium results from disease progression 1
• For cancer patients, consider the distressing nature of delirium for both patients and families, and provide appropriate information and support 1

Common Pitfalls to Avoid

• Assuming all delirium requires pharmacological management - up to 50% of cases resolve with treatment of underlying causes 1
• Using benzodiazepines as initial treatment for non-withdrawal delirium - they are sedating, deliriogenic, and increase fall risk 1
• Overlooking hypoactive delirium, which is often underdiagnosed but is the most prevalent subtype in palliative care patients 1
• Failing to adjust medication approach based on delirium severity and subtype 1