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Bedside Snapshot
  • What it is: Second-generation (atypical) antipsychotic with strong antagonism at 5‑HT2A and D2 receptors; also blocks H1, M1, and α1.
  • Primary ED job: Rapid control of acute agitation/psychosis; ODT is useful; IM formulation for severe agitation.
  • Onset: IM 15–45 min to calming; ODT ~15–60 min; peak sedation varies.
  • Key caution: Avoid giving parenteral benzodiazepines within ~1 hour of IM olanzapine due to respiratory/CNS depression risk.
Boxed warning: Increased mortality in elderly patients with dementia‑related psychosis.
Brand & Generic Names
  • Generic Name: Olanzapine
  • Brand Names: Zyprexa (tablets, ODT), Zyprexa IntraMuscular
Medication Class

Atypical antipsychotic (second‑generation). Antagonist at serotonin 5‑HT2A and dopamine D2 receptors; additional antagonism at histamine H1, muscarinic M1–M5, and α1‑adrenergic receptors explains sedation, anticholinergic, and orthostatic effects.

Pharmacology

Mechanism of Action:

  • 5‑HT2A/D2 receptor antagonism reduces positive symptoms and agitation; lower EPS risk vs typical antipsychotics at usual doses.
  • H1 and M1 blockade contributes to sedation and anticholinergic effects; α1 blockade → orthostatic hypotension.

Pharmacokinetics:

  • Routes: PO tablets/ODT; IM for acute agitation.
  • Onset: IM ~15–45 min; ODT ~15–60 min.
  • Metabolism: Hepatic (CYP1A2, CYP2D6); smoking induces CYP1A2 → may lower exposure.
  • Elimination: Renal and fecal as metabolites; t½ ~21–54 h (longer in elderly/females/non‑smokers).
Indications
  • Acute agitation associated with schizophrenia or bipolar disorder (IM/PO/ODT).
  • Schizophrenia and bipolar I disorder (maintenance PO).
  • Adjunct for chemotherapy‑induced nausea/vomiting (off‑label, per oncology protocols).
Dosing & Administration

Available Forms:

  • Tablets/ODT: 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg, 20 mg.
  • IM injection (agitation): 10 mg/vial (reconstituted); lower doses possible.

Common ED/ICU Dosing (Agitation):

Route Initial Dose Repeat/Max Notes
IM 5–10 mg once May repeat q2–4 h; max 30 mg/day Avoid parenteral benzodiazepines within ~1 h of IM dose.
ODT/PO 5–10 mg May repeat based on response Lower initial dose (2.5–5 mg) in elderly/frail.
Contraindications

Contraindications:

  • Known hypersensitivity to olanzapine.
  • Concomitant parenteral benzodiazepines with IM olanzapine (avoid close temporal co‑administration).

Precautions:

  • Dementia‑related psychosis: Increased mortality risk (boxed warning).
  • Respiratory/CNS depression: Synergistic sedation with benzodiazepines or alcohol; space IM doses by ~1 hour.
  • Orthostatic hypotension: Due to α1 antagonism; use lower doses in elderly or volume‑depleted.
  • Metabolic effects: Weight gain, dyslipidemia, hyperglycemia (more with chronic use).
  • Anticholinergic effects: Dry mouth, constipation, urinary retention, delirium risk in older adults.
  • QT effects: Generally modest; use caution with other QT‑prolonging drugs/electrolyte disturbances.
Adverse Effects

Common:

  • Sedation, dizziness, dry mouth, constipation, increased appetite/weight.

Serious:

  • Neuroleptic malignant syndrome (rare), severe orthostatic hypotension/syncope, severe hyperglycemia/diabetic ketoacidosis, tardive dyskinesia (with chronic use), seizures (rare).
Special Populations
  • Elderly/frail: Start 2.5–5 mg; monitor for orthostasis and sedation.
  • Hepatic impairment: Use lower initial doses and titrate cautiously.
  • Pregnancy/lactation: Use only if benefits outweigh risks; monitor neonate for EPS/withdrawal if exposed late in pregnancy.
  • Smoking: CYP1A2 induction may lower exposure; non‑smokers may require lower doses.
Monitoring

Clinical: Level of agitation, airway/respiratory status, blood pressure/orthostasis, mental status.

Laboratory (longer term): Weight/BMI, fasting glucose/A1c, fasting lipids; consider ECG if multiple QT‑risk factors.

Clinical Pearls
Don’t stack IM olanzapine with IM benzos: Separate by ~1 hour to reduce respiratory depression risk.
Route matters: Use ODT for cooperative patients; IM for severe agitation when IV access is delayed or unsafe.
Elderly dosing: Start low and go slow to avoid orthostasis and oversedation.
References
  • 1. Eli Lilly. (2024). Zyprexa (olanzapine) prescribing information. https://pi.lilly.com/us/zyprexa-pi.pdf
  • 2. Citrome, L. (2017). Olanzapine for acute agitation. Int J Clin Pract, 71(7). https://doi.org/10.1111/ijcp.12964
  • 3. FDA. (2017). Information for healthcare professionals: Olanzapine and benzodiazepines. https://www.fda.gov/
  • 4. AAEP Project BETA. (2012). Best practices in evaluation and treatment of agitation. West J Emerg Med. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3298208/
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