Summary of "Olanzapine as an add-on, pre-operative anti-emetic drug for postoperative nausea or vomiting: a randomised controlled trial"

Summary published October 24, 2023

Summary by Bommy Hong Mershon, MD

Anaesthesia | July 2023

Grigio TR, Timmerman H, Martins JVB, Slullitel A, Wolff AP, Sousa AM. Olanzapine as an add-on, pre-operative anti-emetic drug for postoperative nausea or vomiting: a randomised controlled trial. Anaesthesia. 2023 Oct;78(10):1206-1214. doi: 10.1111/anae.16081. Epub 2023 Jul 14. PMID: 37449978.


  • Postoperative nausea and vomiting (PONV) is a common issue, affecting up to 40% of patients despite prophylactic measures based on risk factors and guidelines. High-risk PONV patients often require multiple antiemetics, including propofol anesthesia, as per consensus guidelines.
  • Olanzapine, primarily an antipsychotic drug, has been used for nausea/vomiting in palliative care and chemotherapy settings. It acts on multiple receptors involved in PONV, including dopaminergic, serotoninergic, and histaminergic receptors, with good oral bioavailability.
  • To investigate its effectiveness in extremely high-risk PONV patients (meeting 3 or 4 Apfel criteria), a randomized controlled trial was conducted. Patients with cancer, a history of chemotherapy-induced nausea and vomiting, and undergoing medium or major surgery were included. They were divided into two groups: one received 10 mg of oral olanzapine (olanzapine group) one hour before surgery, and the other received a placebo (control group). Both groups received TIVA + epidural anesthesia, 4 mg of dexamethasone after induction, and 4 mg of ondansetron at the end of surgery.
  • The primary outcome was the incidence of PONV within 0-24 hours postoperatively, as recommended by Apfel et al. Secondary outcomes included nausea/vomiting incidence at various time points and severe PONV according to the Clinically Important PONV Intensity Scale.
  • The study found a 60% reduction in PONV incidence in the olanzapine group during the first 24 hours (p=0.008), even though both groups received the recommended multimodal antiemetic regimen. Isolated nausea and vomiting in the first 24 hours were also significantly lower in the olanzapine group (10% vs. 53.7%, p=0.002).
  • Patients in the olanzapine group had lower nausea and vomiting incidence between 0-6 hours and 0-24 hours postoperatively. No significant differences were observed between the groups after 24 hours. Clinically important PONV incidence in the first 24 hours was significantly lower in the olanzapine group (2% vs. 27%, p=0.015).
  • While this study focused on oncology patients, a similar trial in non-oncological gynecological or plastic surgery patients also showed a 39% reduction in PONV incidence in the first 24 hours when olanzapine was added to the regimen.
  • PONV imposes a significant burden on patients and healthcare systems. Even with standard prophylactic antiemetics, its incidence remains high. This study suggests that adding atypical antipsychotic medication like olanzapine, which targets multiple PONV receptors, to commonly used intraoperative antiemetic regimens can substantially reduce PONV and alleviate the associated challenges for both patients and healthcare systems.