Olanzapine (Zyprexa)

Olanzapine (Zyprexa)

HALF-LIFE: 21-54 hours
STARTING DOSE: 5mg-10mg PO daily
TARGET DOSING RANGE: 10mg-20mg PO daily
>> Initial 5mg-10mg PO daily
>> Increase dose by 5mg per day each week to target dose of 10mg-20mg per day
>> Max approved dose 20mg/day (some patients may require up to 60mg/day)
>> For Bipolar depression:
Initial 6mg/25mg PO QHS
Increase to target dose range of olanzapine (6mg-12mg) / Fluoxetine (25mg-50mg) PO daily
PREGNANCY: Minimal data on safety.
BREASTFEEDING: Minimal data on safety.
1) Schizophrenia, 13yo and older
2) Bipolar mania (monotherapy and adjunctive), 13yo and older
3) Bipolar maintenance (monotherapy)
4) Acute agitation in schizophrenia or bipolar (Intramuscular formulation only)
5) Bipolar depression (with fluoxetine*), 13yo and older
6) Treatment resistant unipolar depression (with fluoxetine*)

*Olanzapine-Fluoxetine combination = Symbyax)


  • Formulations: PO, IM
    • PO: Tablet or Orally Disintegrating Tablets (ODT, zydis)IM: Intramuscular and Depot (relprevv) injections available
  • Olanzapine has been studied and found helpful for chemotherapy induced nausea and vomiting
  • Improvement in mood in Schizophrenia, Bipolar, and Refractory depression hypothetically due to effects at 5HT2C, 5HT7, and α2 receptors.
  • Olanzapine + Fluoxetine have possibly synergistic antidepressant effects due to both targeting 5HT2C receptors
  • Dose related EPS risk
  • Low risk for prolactin elevation
  • Sedation (dose dependent) is common due to antagonism at M1, H1, and α1 receptors
  • Dry mouth (dose related) is common
  • Weight gain is common due antagonism at H1 and 5HT2C receptors
    • 10-30 lbs weight gain common
  • Low risk for QTc prolongation
  • High cardio-metabolic risk (↑triglycerides, insulin resistance)
  • Orally disintegrating tablets (ODT, zydis) may reduce potential for weight gain
  • Metabolized by CYP1A2 and, to a lesser extent, CYP2D6
    • Also metabolized by direct glucuronidation (Phase II)


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