Mechanism of Action: Olanzapine for Postoperative Nausea and Vomiting
Olanzapine (Zyprexa) works to stop postoperative nausea through broad-spectrum antagonism of multiple neurotransmitter receptors involved in the emetic pathway, including dopamine (D2), serotonin (5-HT2A, 5-HT3), histamine (H1), and muscarinic receptors, providing a multimodal antiemetic effect through a single agent. 1, 2
Receptor Antagonism Profile
Olanzapine's antiemetic efficacy stems from its action at several key receptor sites:
Dopamine D2 receptor blockade in the chemoreceptor trigger zone (CTZ) prevents activation of the vomiting center, similar to traditional dopamine antagonists like metoclopramide but with broader receptor coverage 1, 3
Serotonin receptor antagonism (5-HT2A and 5-HT3) blocks both central and peripheral serotonergic pathways that mediate nausea, complementing the mechanism of ondansetron which only targets 5-HT3 receptors 1, 2
Histamine H1 receptor blockade provides additional antiemetic activity through the vestibular system and vomiting center, addressing motion-related and central causes of nausea 3
Muscarinic receptor antagonism contributes to the overall antiemetic effect by blocking cholinergic pathways involved in the emetic reflex 3
Clinical Evidence in Postoperative Settings
The most compelling evidence demonstrates olanzapine's effectiveness when added to standard prophylaxis:
In high-risk surgical patients (those with 3-4 Apfel risk factors), a single preoperative dose of olanzapine 10 mg combined with dexamethasone and ondansetron reduced PONV incidence from 63% to 26% in the first 24 hours postoperatively (RR 0.40,95% CI 0.21-0.79, p=0.008) 1
For ambulatory surgery patients, olanzapine 10 mg added to standard dual prophylaxis (dexamethasone plus ondansetron) reduced postdischarge nausea and vomiting from 38% to 14% (RR 0.37,95% CI 0.20-0.72, p=0.003), representing approximately a 60% risk reduction 2
The drug appears particularly effective in patients with previous chemotherapy-induced nausea or multiple PONV risk factors, where standard dual-agent prophylaxis often fails 1
Comparison to Standard Antiemetics
Olanzapine offers distinct advantages over conventional agents:
Standard first-line agents (ondansetron, dexamethasone) each provide approximately 25% relative risk reduction when used individually, with combination therapy improving efficacy 4, 5
Olanzapine's multi-receptor antagonism provides broader coverage than single-mechanism agents, potentially explaining its superior efficacy in high-risk patients who fail standard dual prophylaxis 1, 3
Unlike 5-HT3 antagonists alone, olanzapine addresses dopaminergic, histaminergic, and cholinergic pathways simultaneously, which may be particularly relevant in the complex postoperative setting where multiple emetic triggers are present 3
Practical Dosing and Administration
For postoperative nausea prevention:
Administer 10 mg orally 1 hour preoperatively as an add-on to standard dual prophylaxis (dexamethasone 4-5 mg plus ondansetron 4 mg) in high-risk patients 1, 2
This timing allows adequate absorption and receptor occupancy before surgical stimulation of emetic pathways 1
The single preoperative dose provides antiemetic coverage extending through the critical first 24 hours postoperatively 1, 2
Important Caveats and Side Effects
Sedation is the primary trade-off: Patients receiving olanzapine report slightly higher sedation scores (median 6/10 vs 4/10 on a 0-10 scale) in the 24 hours after discharge, though this increase is modest and may be acceptable given the substantial reduction in nausea and vomiting 2
The sedative effect may actually be beneficial in the immediate postoperative period for anxious patients, but should be considered when planning discharge timing for ambulatory surgery 2
Olanzapine is not currently included in standard ERAS guidelines for routine PONV prophylaxis, which recommend ondansetron plus dexamethasone as first-line dual therapy 4, 5
Reserve olanzapine for high-risk patients (≥3 Apfel risk factors) who have failed or are predicted to fail standard dual prophylaxis, rather than using it as routine first-line therapy 1, 2