What is the recommended dosing for Zyprexa (olanzapine)?

Zyprexa (Olanzapine) Dosing

For most adults with schizophrenia or bipolar disorder, start with 5-10 mg once daily and target 10 mg/day, with a maximum dose of 20 mg/day. 1

Adult Dosing by Indication

Schizophrenia

• Starting dose: 5-10 mg once daily (oral), without regard to meals 1
• Target dose: 10 mg/day within several days 1
• Dose adjustments: Increase or decrease by 5 mg increments, with at least 1 week between adjustments (time to steady state) 1
• Effective range: 10-15 mg/day demonstrated efficacy in trials, though doses above 10 mg/day were not more effective than 10 mg/day 1
• Maximum dose: 20 mg/day; olanzapine is not indicated above this dose 1

Bipolar I Disorder (Manic or Mixed Episodes)

• Monotherapy starting dose: 10-15 mg once daily 1
• Adjunctive therapy (with lithium or valproate): Start with 10 mg once daily 1
• Dose adjustments: 5 mg increments/decrements, with at least 24 hours between changes 1
• Effective range: 5-20 mg/day 1
• Maximum dose: 20 mg/day; safety above this has not been evaluated 1

Acute Agitation (Intramuscular)

• Recommended dose: 10 mg IM 1
• Lower doses: 5 mg or 7.5 mg may be considered when clinical factors warrant 1
• Repeat dosing: Additional doses up to 10 mg may be given if agitation persists, but no more frequently than 2 hours after the first dose and 4 hours after the second dose 1
• Maximum daily dose: 30 mg total; higher doses or more frequent administration have not been evaluated 1

Special Populations

Elderly or Debilitated Patients

• Starting dose: 5 mg orally or 2.5-5 mg IM 1
• Maximum dose: 20 mg/day (oral), though lower doses are often effective 2
• Rationale: Increased risk of adverse effects including hypotension and metabolic complications 3

Dementia-Related Agitation

• Starting dose: 2.5 mg once daily at bedtime 2
• Maximum dose: 10 mg/day, usually divided into twice-daily dosing 2
• Important caveat: Olanzapine carries a black box warning for increased mortality in elderly patients with dementia-related psychosis

Hepatic Impairment

• Starting dose: 2.5 mg daily to minimize toxicity risk 3

Pharmacodynamically Sensitive Patients

• Starting dose: 5 mg orally or 2.5 mg IM for nonsmoking females ≥65 years or those predisposed to hypotensive reactions 1

Adolescent Dosing (Ages 13-17)

Schizophrenia or Bipolar I Disorder

• Starting dose: 2.5-5 mg once daily 1
• Target dose: 10 mg/day 1
• Dose adjustments: 2.5-5 mg increments 1
• Effective range: 2.5-20 mg/day (mean modal dose 11-12.5 mg/day in trials) 1
• Maximum dose: 20 mg/day; safety and efficacy above this have not been established 1

Critical Safety Considerations

Combination with Benzodiazepines

• Exercise extreme caution when combining olanzapine with benzodiazepines due to risk of oversedation and respiratory depression 3
• Fatalities have been reported with concurrent use of benzodiazepines and high-dose olanzapine, particularly with IM administration 3
• When using IM olanzapine 10 mg with lorazepam 2 mg IM, assess for orthostatic hypotension before subsequent doses 1

Orthostatic Hypotension Monitoring

• Maximal IM dosing (three 10 mg doses given 2-4 hours apart) is associated with substantial orthostatic hypotension 1
• Assess for postural blood pressure changes before administering subsequent IM doses 1
• Do not give additional doses if clinically significant postural hypotension is present 1

Evidence for Higher Doses

While the FDA-approved maximum is 20 mg/day, some evidence suggests potential benefit of higher doses in specific circumstances:

• Treatment-resistant patients: Case reports describe successful use of 35-60 mg/day in treatment-refractory schizophrenia, though this is off-label 4
• Highly symptomatic patients: A randomized trial comparing 10,20, and 40 mg/day found that patients with higher baseline symptom severity responded better to higher doses 5
• Increased risks at 40 mg/day: Significantly more weight gain (3.0 kg vs 1.9 kg) and elevated prolactin compared to 10 mg/day 5
• Clinical practice patterns: Over 50% of hospitalized patients in New York State psychiatric centers received doses exceeding 20 mg/day by 2006, though this exceeds FDA recommendations 6

For standard clinical practice, adhere to the FDA-approved maximum of 20 mg/day unless treating truly refractory patients under close monitoring. 1