What is the maximum daily dose of Zyprexa (olanzapine)?

Maximum Daily Dose of Zyprexa (Olanzapine)

The maximum recommended daily dose of Zyprexa (olanzapine) is 20 mg/day for adults with schizophrenia or bipolar I disorder, as olanzapine is not indicated for use in doses above 20 mg/day. 1

Standard Dosing by Indication

Schizophrenia - Adults

• Target dose: 10 mg/day, with a maximum of 20 mg/day 2, 1
• Initial dosing: 5-10 mg once daily, reaching target dose within several days 1
• Efficacy demonstrated in the 10-15 mg/day range, though doses above 10 mg/day were not more efficacious than 10 mg/day 1
• Dose adjustments should occur at intervals of at least 1 week (time to steady state) in increments/decrements of 5 mg 1

Schizophrenia - Adolescents

• Target dose: 10 mg/day, with a maximum of 20 mg/day 1
• Starting dose: 2.5-5 mg once daily 1
• Mean modal dose in clinical trials: 12.5 mg/day 1
• Dose adjustments in 2.5 or 5 mg increments 1

Bipolar I Disorder (Manic or Mixed Episodes) - Adults

• Dose range: 5-20 mg/day, with maximum of 20 mg/day 1
• Initial dosing: 10-15 mg once daily 1
• Dose adjustments at intervals of at least 24 hours in 5 mg increments 1

Bipolar I Disorder - Adolescents

• Starting dose: 2.5-5 mg once daily 1
• Dose adjustments in 2.5 or 5 mg increments as needed 1

Special Population Dosing

Elderly or Debilitated Patients

• Starting dose: 2.5-5 mg/day, with maximum of 20 mg/day 2, 1
• Lower doses often effective; titrate cautiously 2
• Recommended for patients ≥65 years (especially nonsmoking females), those with hypotensive predisposition, or slower metabolism 1

Alzheimer's Disease/Dementia

• Starting dose: 2.5 mg once daily at bedtime 2
• Maximum dose: 10 mg/day (usually divided twice daily) 2
• This represents a significantly lower ceiling than the general adult population 2

Off-Label High-Dose Use: Critical Caveats

While the FDA-approved maximum is 20 mg/day 1, some treatment-resistant patients have been treated with higher doses:

• Case reports describe successful treatment at 35-60 mg/day in treatment-resistant schizophrenia without significant side effects 3
• A large randomized trial comparing 10 vs 20 vs 40 mg/day found increased risk of weight gain and elevated prolactin at 40 mg/day 4
• Clinical practice data from New York State psychiatric centers showed average doses increased from 17.4 to 22.5 mg/day between 1997-2003, with over 50% of patients receiving >20 mg/day by 2006 4
• High-dose use (>20 mg/day) may be considered only in selected treatment-resistant patients with severe/persistent symptoms, but this exceeds FDA-approved dosing and carries increased metabolic risks 4

Key Safety Considerations

• QTc prolongation occurs at maximum recommended doses, though olanzapine has the least effect among atypical antipsychotics studied 5
• Weight gain and metabolic side effects are dose-dependent, particularly at doses ≥40 mg/day 4
• Extrapyramidal symptoms are significantly less common than with conventional antipsychotics at approved doses 6
• No association with agranulocytosis (unlike clozapine) or clinically significant hyperprolactinemia (unlike risperidone) at standard doses 6