Is olanzapine (an atypical antipsychotic) effective for treating refractory nausea?

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Last updated: April 27, 2025View editorial policy

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From the Guidelines

Olanzapine is a highly effective option for refractory nausea, particularly when first-line antiemetics have failed, with a recommended dosage of 10 mg given once before chemotherapy, then daily for 3 days, as part of a 4-drug regimen including aprepitant or fosaprepitant, a 5-HT3 antagonist, and dexamethasone 1. The use of olanzapine in this context is supported by a phase III randomized trial that demonstrated a significant increase in the complete response rate (no emesis, no rescue) compared to placebo during the overall 120-hour period 1. Key benefits of olanzapine include its ability to target multiple receptors involved in nausea and vomiting pathways, making it effective in cases resistant to single-pathway antiemetics 1. Common side effects associated with olanzapine are mostly tolerable and mild, with somnolence, postural hypotension, constipation, dizziness, fatigue, dyspepsia, and restlessness most commonly reported 1. When initiating treatment with olanzapine, it is essential to start with a lower dose (2.5 mg) in elderly patients or those sensitive to side effects and titrate up as needed, while also being cautious of potential drug-drug interactions and monitoring for metabolic effects with long-term use 1. Overall, olanzapine can be a valuable addition to the treatment regimen for patients with refractory nausea, particularly in chemotherapy-induced nausea, palliative care settings, and postoperative nausea refractory to conventional treatments.

From the Research

Olanzapine for Refractory Nausea

  • Olanzapine is an atypical antipsychotic agent that has been used to treat schizophrenia and delirium, and has also been found to be effective in treating nausea and vomiting refractory to standard antiemetics 2, 3.
  • The drug blocks multiple neurotransmitter receptors, including dopaminergic, serotonergic, adrenergic, histaminergic, and muscarinic receptors, which are involved in causing emesis 2, 3.
  • Studies have shown that olanzapine can be used to treat chronic nausea, prevent chemotherapy-induced nausea and emesis, and treat breakthrough chemotherapy-induced nausea and emesis 2, 4.
  • Common side effects of olanzapine include weight gain and an association with the onset of diabetes mellitus, but these effects have not been seen with short-term use of daily doses of less than one week 2.
  • Olanzapine has been found to be effective in treating refractory non-chemotherapy-induced nausea and vomiting (non-CINV), although the evidence is limited to case reports, series, retrospective studies, and one pilot study 4.

Comparison with Other Antiemetics

  • Ondansetron, a selective serotonin 5-HT3 receptor antagonist, is also used to treat nausea and vomiting associated with cancer chemotherapy, radiotherapy, or anesthesia and surgery 5, 6.
  • Unlike olanzapine, ondansetron is generally well tolerated with a lower incidence of sedation and only isolated case reports of extrapyramidal reactions 5, 6.
  • However, ondansetron may not be as effective in treating refractory nausea and vomiting, and olanzapine may be a useful alternative in these cases 2, 4.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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