What is the appropriate PRN dose of olanzapine for an adult with acute delirium and agitation?

PRN Olanzapine Dosing for Acute Delirium with Agitation

For acute delirium with agitation in adults, start with olanzapine 2.5–5 mg orally or subcutaneously as a single PRN dose, with the option to repeat every 1–2 hours if agitation persists, using lower doses (2.5 mg) in elderly or frail patients. 1

Initial Dose Selection

• The recommended starting dose is 2.5–5 mg orally or subcutaneously for most adults with acute agitated delirium. 1

• For intramuscular administration in severe agitation, the FDA-approved dose is 10 mg IM, though lower doses of 5 or 7.5 mg may be considered when clinical factors warrant. 2

• Elderly, frail, or medically compromised patients should receive 2.5 mg as the initial dose to minimize risks of orthostatic hypotension, oversedation, and falls. 1, 2

Repeat Dosing Strategy

• If agitation persists after the initial dose, subsequent doses up to 10 mg may be given, with a minimum interval of 2 hours between the first and second dose, and 4 hours between the second and third dose. 2

• The total daily dose should not exceed 30 mg, and doses should not be given more frequently than every 2–4 hours, as maximal dosing (three 10 mg injections) is associated with substantial orthostatic hypotension. 2

• Assess for orthostatic hypotension (clinically significant postural drop in systolic blood pressure) before administering any subsequent dose; do not give additional doses if orthostatic changes are present. 2

Route-Specific Considerations

Oral/Sublingual Administration

• Olanzapine is available as an orally disintegrating tablet (ODT), which is useful when patients cannot or will not swallow pills. 1

• Oral dosing of 2.5–5 mg can be given at bedtime if scheduled dosing is required, though PRN dosing is preferred for acute agitation. 1

Subcutaneous Administration

• Subcutaneous olanzapine 5 mg every 8 hours has been studied in cancer patients with agitated delirium and is well tolerated without injection site toxicity. 3

• The subcutaneous route is particularly appropriate for terminally ill or thrombocytopenic patients where intramuscular injection poses bleeding risk. 3

Intramuscular Administration

• The FDA-approved IM dose for acute agitation is 10 mg, with efficacy demonstrated in the 2.5–10 mg range. 2

• IM olanzapine should be injected slowly and deeply into muscle mass; it is not approved for intravenous or subcutaneous use per FDA labeling, though off-label subcutaneous and IV use has been reported. 2, 3, 4

Critical Safety Warnings

Combination with Benzodiazepines

• Concurrent use of olanzapine with benzodiazepines carries a risk of excessive sedation and respiratory depression; this combination should be used with extreme caution or avoided. 1

• If benzodiazepines are absolutely necessary, start at the lowest doses and monitor closely for oversedation. 5

Cardiovascular Monitoring

• Olanzapine may cause orthostatic hypotension and drowsiness, particularly with repeated dosing or in elderly patients. 1, 2

• QTc prolongation is less common with olanzapine than with haloperidol, making it a reasonable choice when QTc is already prolonged. 4

Extrapyramidal Symptoms

• Although olanzapine has a lower risk of extrapyramidal side effects (EPSEs) compared to first-generation antipsychotics, akathisia and other movement disorders can still occur, especially at higher doses (≥15 mg daily). 6

• Restlessness in a patient receiving olanzapine should prompt assessment for akathisia rather than assumption of worsening delirium; if suspected, reduce or discontinue the antipsychotic. 6

Special Populations

• Do not use olanzapine in patients with Parkinson's disease or dementia with Lewy bodies due to severe sensitivity to antipsychotics. 1

• Reduce doses in patients with hepatic impairment. 1, 2

• Elderly patients with dementia-related psychosis have an increased mortality risk with all antipsychotics; olanzapine is not FDA-approved for this indication. 2

Comparative Efficacy

• Olanzapine is as effective as haloperidol for controlling agitation in psychiatric conditions (90% vs 94% sedation within 20 minutes) and superior in agitation from organic medical causes (79% vs 25%). 7

• In acute undifferentiated agitation, IM olanzapine 10 mg sedated 79% of patients within 20 minutes, with the remainder sedated after a repeat dose within 45 minutes. 7

• Olanzapine is slightly less effective than haloperidol for alcohol intoxication and traumatic brain injury, though differences are not statistically significant. 7

Transition to Oral Therapy

• Once acute agitation is controlled, transition to oral olanzapine 5–20 mg daily as soon as clinically appropriate. 2

• Scheduled oral dosing is typically given at bedtime due to sedating effects. 1

Common Pitfalls to Avoid

• Do not administer olanzapine more frequently than every 2 hours without reassessing for orthostatic hypotension and level of sedation. 2

• Do not combine high-dose olanzapine with high-dose benzodiazepines due to fatal outcomes reported with this combination. 5

• Do not assume all restlessness is worsening delirium; consider drug-induced akathisia, especially if symptoms emerge or worsen after dose escalation. 6

• Do not use olanzapine as first-line for alcohol withdrawal delirium; benzodiazepines remain the standard of care for that specific indication. 8