What is the treatment approach for delirium?

Treatment of Delirium

Primary Treatment Approach

Non-pharmacological interventions should be the first-line treatment for delirium, with pharmacological management reserved primarily for severe agitation that poses safety risks. 1, 2

The treatment of delirium follows a structured algorithm that prioritizes identifying and reversing underlying causes, implementing multicomponent non-pharmacological strategies, and using medications judiciously only when necessary for symptom control.

Step 1: Identify and Reverse Underlying Causes

All patients with delirium require comprehensive assessment to identify precipitating factors that can be reversed. 3, 1, 2

Key reversible causes to evaluate:

• Metabolic derangements: hypoxia, electrolyte imbalances, hypoglycemia, dehydration 2
• Infections: urinary tract infection, pneumonia, or other sources 2
• Medications: discontinue or reduce anticholinergics, benzodiazepines, steroids, and opioids 3, 2
• Urinary retention or constipation (particularly in elderly patients) 2
• Hypercalcemia: treat with IV bisphosphonates (pamidronate or zoledronic acid) 3, 1
• SIADH: discontinue implicated medications, implement fluid restriction, ensure adequate oral salt intake 3, 1
• Hypomagnesemia: provide magnesium replacement 3, 1
• Opioid-induced neurotoxicity: consider opioid rotation to fentanyl or methadone (reduce equianalgesic dose by 30-50%) 3, 1

Step 2: Non-Pharmacological Interventions (First-Line Treatment)

Multicomponent non-pharmacological strategies are the primary treatment approach and should be maximized before considering medications. 3, 2

Essential interventions include:

• Reorientation strategies: use clocks, calendars, familiar objects, and ensure family presence 2
• Optimize sensory function: provide hearing aids and eyeglasses if normally used 2
• Sleep hygiene: minimize nighttime noise and light, cluster care activities 3, 2
• Early mobilization: encourage out-of-bed activity as tolerated 2
• Maintain adequate hydration and nutrition 2
• Remove unnecessary tubes, catheters, and other iatrogenic factors 1, 2
• Cognitive stimulation 3

Step 3: Pharmacological Management (Reserved for Specific Indications)

Critical Evidence on Antipsychotic Use

Haloperidol and risperidone have NO demonstrable benefit in mild-to-moderate delirium and are NOT recommended in this context. 3, 1 This is a crucial finding from high-quality evidence that contradicts older practices.

When to Use Pharmacological Treatment

Medications should be reserved for severe agitation that poses safety risks to the patient or staff, as routine antipsychotic use does not improve delirium outcomes and may cause harm. 2

Medication Options for Severe Delirium

For severe delirium with agitation:

• Haloperidol: 0.5-2 mg every hour as needed until episode is controlled, then 0.5-1 mg twice daily for maintenance 1, 2
  • Monitor for QT prolongation and extrapyramidal side effects 2
  • Can be administered orally or IV 2

Alternative antipsychotics (may offer benefit with fewer extrapyramidal side effects):

• Olanzapine: 2.5-15 mg daily; offers sedation benefit in hyperactive delirium 3, 1, 2
• Quetiapine: 25-100 mg twice daily; may be preferable for hypoactive delirium due to sedating properties 3, 1, 2
• Aripiprazole: may offer benefit but less evidence 3

Refractory Agitation

For agitation refractory to high doses of antipsychotics, add lorazepam 0.5-2 mg every 4-6 hours. 1, 2 However, benzodiazepines should NOT be used as initial treatment for delirium in patients not already taking them, as they can worsen confusion and increase fall risk. 3, 2

The exception is alcohol or benzodiazepine withdrawal-related delirium, where benzodiazepines are the drugs of choice. 2

Hypoactive Delirium

Methylphenidate may improve cognition in hypoactive delirium without delusions or perceptual disturbances and for which no cause has been identified. 3, 1

Step 4: Monitoring and Duration

Use the lowest effective dose for the shortest duration possible, and discontinue antipsychotics immediately once acute distressing symptoms resolve. 2

• Daily delirium assessment using validated tools (DSM-IV criteria or validated screening instruments) 3, 1
• Reassess need for continued pharmacological intervention daily 2

Treatment Algorithm Based on Life Expectancy

For patients with years to live:

• Screen for delirium using DSM criteria 1
• Treat all underlying reversible causes 1
• Focus on complete resolution 1

For dying patients (weeks to days):

• Evaluate for iatrogenic causes 1
• Focus on symptom control and family support 3, 1
• Consider appropriate upward dose titration of medications for comfort 1
• For refractory delirium, palliative sedation can be considered after consultation with palliative care specialist and/or psychiatrist 3

Critical Pitfalls to Avoid

Hypoactive delirium is often underdiagnosed due to its subtle presentation and is the most prevalent subtype in palliative care patients. 3, 1 Maintain high index of suspicion.

Agitation may be mistaken for pain, resulting in higher opioid doses which worsen delirium. 1 Distinguish carefully between pain and delirium-related agitation.

Benzodiazepines alone can worsen delirium and should only be used for alcohol/sedative withdrawal or when agitation is refractory to antipsychotics. 1

Delirium in patients with advanced cancer and limited life expectancy may shorten prognosis. 3, 1 Adjust goals of care accordingly.

Family Support and Education

Provide written information supplemented with educational and psychological support for families by suitably trained staff. 3 Relatives should have access to information about delirium pre-emptively and at repeated intervals, especially if the patient's condition is declining. 3