Olanzapine (Zyprexa)


Clinical Information


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.

Side Effects

  • Dry mouth, sedation, orthostatic hypotension, fatigue, Neuroleptic Malignant Syndrome (rare), weight gain, metabolic side effects (dyslipidemia, insulin resistance), prolactin elevation, akathisia/restlessness, abnormal movements, seizures (rare)

FDA Indications

  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)

Mechanism(s) of Action

  • Dopamine 2 (D2) Receptor antagonism, 5HT2A Receptor antagonism, 5HT2C Receptor Antagonism, Antihistaminic effects, alpha-1 receptor antagonism

Additional Information

  • Comes in a Tablet or Orally Disintegrating Tablets (ODT, zydis), Intramuscular injection, and Depot (relprevv) injection
  • Olanzapine has been studied and found helpful for chemotherapy induced nausea and vomiting
  • Improvement in mood in Schizophrenia, Bipolar, and Refractory depression
  • Olanzapine + Fluoxetine have possibly synergistic antidepressant effects due to 5HT2C/5HT2A properties
  • Dose related risk for extrapyramidal symptoms (e.g., dystonia, parkinsonism)
  • Low risk for prolactin elevation
  • Sedation (dose dependent) is common 
  • Dry mouth (dose related) is common
  • Weight gain is common (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


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