Low dose olanzapine cuts chemo-induced nausea without causing sedation

Low-dose (5mg) olanzapine reduces chemo-induced nausea in breast cancer patients without causing sedation, researchers reported on July 1, 2025 in The Lancet Oncology.

As background for this study, lead investigator Professor Mitsue Saito from Juntendo University, Japan said, “While multiple studies have examined 10 mg of olanzapine and confirmed its effectiveness for nausea control, at this dose it often causes sedation, raising safety concerns. Beyond the commonly observed sedation, olanzapine at the 10 mg dose can cause serious adverse effects, including sedative effects such as daytime sleepiness and loss of consciousness.”

The authors explained that the aim of their study was to show whether 5 mg of olanzapine taken at home after anthracycline plus cyclophosphamide chemotherapy rather than before chemotherapy would maintain efficacy in controlling chemotherapy-induced nausea and vomiting and minimize sedative side-effects.

In this phase 3, placebo-controlled Japanese trial the researchers enrolled 500 female subjects with breast cancer receiving outpatient anthracycline plus cyclophosphamide-based chemotherapy.

They randomized the subjects to receive either olanzapine 5 mg (n=250) or placebo (n=250) in combination with standard triplet antiemetic therapy (palonosetron, dexamethasone, and an NK-1 receptor antagonist).

Olanzapine 5 mg was self-administered at home after chemotherapy, to avoid sedation during travel or treatment.

The primary endpoint was the proportion of patients with a complete response, defined as no vomiting and no rescue medication during the overall phase (0–120 hours) after the initiation of anthracycline plus cyclophosphamide.

The investigators reported that 480 subjects (246 in the olanzapine group and 234 in the placebo group) received at least one dose of study medication and were eligible for the efficacy analysis.

The complete response rate in the olanzapine group (58.1%, n=143) was statistically significantly higher than in the placebo group (35.5%, n=83; difference 22.7%, p<0·0001).

The authors noted, “While some patients reported drowsiness, the incidence of severe or very severe concentration impairment was low, occurring in 10% of patients in the olanzapine 5 mg group vs. 14% in the placebo group. Additionally, no major adverse events were observed in either group, indicating that there were no treatment-related deaths in either group.”

The authors concluded, “The results demonstrated significant improvement, with 58.1% of patients in the olanzapine 5 mg group achieving a complete response during the first 5 days after chemotherapy, compared to only 35.5% in the placebo group. Benefits also extended to delayed nausea and vomiting across a 7-day observation period.”