Olanzapine

Clinical question 2e:

What is the effect of olanzapine in the treatment of nausea and/or vomiting in patients in the palliative phase of cancer, heart failure, COPD, MS, ALS or renal failure?

Recommendation

Treatment with olanzapine orally is recommended for patients in the palliative phase with nausea and/or vomiting that responds insufficiently to other antiemetics.

Introduction

Olanzapine is an antipsychotic agent with antidopaminergic, antiadrenergic, antiserotonergic, anticholinergic and antihistaminic action [Licup 2010]. It is administered in oral (as tablet, also orodispersable) or intramuscular form (for delayed release).
It is not registered in the Netherlands for the treatment of nausea and vomiting.

In the following text, the role of olanzapine in the prevention and treatment of nausea and vomiting as a result of chemotherapy or an ileus will not be discussed.

Literature discussion

During the literature research, a pilot study [Passik 2002], two case series [Jackson 2003; Srivastava 2003] and a systematic review [Davis 2010] were found.
Passik researched 15 patients with an advanced stage of cancer with nausea (NRS score 4-8 on a scale of 0-10) and stable pain, treated with opioids [Passik 2002]. Data on earlier treatment with antiemetics was not reported. Patients did not use other antiemetics during the study. Olanzapine was administered (after two days of treatment with placebo) in successive doses of 2.5, 5 and 10 mg orally once daily, each dose for a duration of 2 days. A significant reduction in nausea was seen at all dose levels. No extrapyramidal side effects or cognitive function disorders occurred.

Jackson described six patients (four with cancer, one with CVA and one with dementia) with therapy-resistant nausea [Jackson 2003]. After treatment with olanzapine 2.5-5 mg orally in the evenings, there was a strong improvement in nausea complaints.
Srivastava described two patients with an advanced stage of cancer and nausea and vomiting, resistant against other antiemetics [Srivastava 2003]. After treatment with olanzapine 5 mg once daily, there was a marked improvement in the nausea and vomiting. Sedation was the most common side effect.

The systematic review concluded that olanzapine is an effective antiemetic on the basis of prospective uncontrolled research [Davis 2010].

There are indications that olanzapine is an effective antiemetic for patients with an advanced stage of cancer, who have responded insufficiently to earlier antiemetics.
[Jackson 2003; Passik 2002; Srivastava 2003]

Olanzapine has only been studied in a few patients with diseases other than cancer. However, there is no reason to assume that it would be less effective in other diseases. For the (rare) patient with therapy-resistant nausea and/or vomiting and a disease other than cancer, treatment with olanzapine may therefore also be considered. It is recommended to administer the lowest possible effective dose, due to possible drowsiness as side effect.

In clinical practice, olanzapine is less commonly used than levomepromazine.