Zyprexa (Olanzapine) Dosing for Agitation
For acute agitation in adults, intramuscular olanzapine 10 mg is the recommended dose, with 5 mg considered for geriatric patients or those with clinical factors warranting dose reduction. 1
Dosing by Route and Population
Intramuscular Administration (Acute Agitation)
Standard adult dose: 10 mg IM is the FDA-approved dose for agitation associated with schizophrenia and bipolar I mania 1. A lower dose of 5 or 7.5 mg may be considered when clinical factors warrant 1.
Geriatric patients: 5 mg IM should be considered as the initial dose 1. Critical caveat: Patients over 75 years respond less well to olanzapine, and short-term treatment is associated with increased mortality 2.
Debilitated or hypotension-prone patients: 2.5 mg IM should be considered for patients who are debilitated, predisposed to hypotensive reactions, or more pharmacodynamically sensitive to olanzapine 1.
Repeat dosing: If agitation persists, subsequent doses up to 10 mg may be given, but assess for orthostatic hypotension prior to each subsequent dose 1. Maximum of 3 doses administered 2-4 hours apart (total daily maximum 30 mg) 1. Maximal dosing may be associated with substantial orthostatic hypotension 1.
Oral Administration (Acute Agitation)
Rapid initial dose escalation (RIDE) strategy: Up to 40 mg/day oral olanzapine on days 1-2, up to 30 mg on days 3-4, then 5-20 mg thereafter 3. This approach demonstrated superior efficacy compared to standard dosing (10 mg/day) at 24 hours in acutely agitated patients 3.
Standard oral dosing: 10-20 mg/day, with accelerated titration to 20 mg as early as day 3 showing efficacy when combined with adjunctive lorazepam (up to 12 mg/day) 4.
Initial oral dose for schizophrenia: Start at 5-10 mg once daily, with target of 10 mg/day within several days 1.
Intravenous Administration (Off-Label)
Off-label IV dosing: 2.5-10 mg IV bolus (maximum 30 mg/day) has been used off-label, with efficacy similar to droperidol in achieving adequate sedation within 10 minutes 5. However, this remains controversial in the absence of FDA approval 5.
Age-Specific Considerations
Elderly patients (especially >75 years): Use the lowest effective dose for the shortest duration 2. These patients respond less well to olanzapine and face increased mortality risk 2. For IM administration, start with 5 mg 1.
Adolescents (bipolar mania): Start at 2.5-5 mg once daily, with target dose of 10 mg/day 1.
Critical Safety Warnings
Black box warning considerations: All antipsychotics increase mortality risk in elderly patients with dementia (1.6-1.7 times higher than placebo) 2. Discuss this risk with patients or surrogates before initiating treatment 2.
Cardiovascular risks: Monitor for QT prolongation, dysrhythmias, sudden death, and hypotension 2. Assess for orthostatic hypotension before subsequent IM doses 1.
Combination with benzodiazepines: Extreme caution is advised due to reported fatalities with concomitant use of benzodiazepines and high-dose olanzapine 6. When combining IM olanzapine with lorazepam, administer separately 7.
Metabolic effects: Monitor for falls, pneumonia, and metabolic changes 2.
Clinical Context and Alternatives
Non-pharmacological interventions first: Behavioral interventions must be attempted and documented as failed before using antipsychotics, unless there is imminent risk of harm 2. Address reversible causes including pain, infections, constipation, and dehydration 2.
When olanzapine is preferred: Olanzapine is superior to haloperidol in agitation secondary to organic medical conditions (79.1% vs 25% sedated within 20 minutes) 8. It is as efficacious as haloperidol with lorazepam in psychiatric agitation (90% vs 94.1% sedated within 20 minutes) 8.
When haloperidol may be preferred: In alcohol intoxication and traumatic brain injury, haloperidol 5 mg shows slightly better efficacy than olanzapine, though not statistically significant 8. Haloperidol 0.5-1 mg is recommended as first-line for acute agitation in geriatric patients 2.
Duration of treatment: Use at the lowest effective dose for the shortest possible duration, with daily reassessment 2. Evaluate response within 4 weeks and taper if no clinically significant benefit 2.
Transition to oral therapy: Once agitation is controlled, transition to oral olanzapine 5-20 mg/day as soon as clinically appropriate 1.