Olanzapine for the prevention and treatment of chronic nausea and chemotherapy-induced nausea and vomiting

摘要

Olanzapine is an atypical antipsychotic agent of the thiobenzodiazepine class. It blocks multiple neurotransmitter receptors including dopaminergic at D_1, D_2, D_3, D_4 brain receptors, serotonergic at 5-HT_(2a), 5-HT_(2c) 5-HT_3, 5-HT_6 receptors, catecholamines at alpha_1 adrenergic receptors, acetylcholine at muscarinic receptors, and histamine at H_1 receptors. Olanzapine has five times the affinity for 5-HT_2 receptors than D_2 receptors and has been used to treat schizophrenia and delirium. Olanzapine's activity at multiple receptors, particularly at the D_2, 5-HT_(2c), and 5-HT_3 receptors which appear to be involved in nausea and emesis, has prompted its use in the treatment of nausea and vomiting refractory to standard antiemetics. Case reports and formal clinical trials have demonstrated its efficacy in the treatment of chronic nausea, the prevention of chemotherapy-induced nausea and emesis, and the treatment of breakthrough chemotherapy-induced nausea and emesis. Phase II and phase III clinical trials have demonstrated that there is a significant improvement in nausea when olanzapine is added to guideline directed prophylactic antiemetic agents 5-HT_3 receptor antagonists and tachykinin NK_1receptor antagonists in patients receiving moderately or highly emetogenic chemotherapy Common side effects of olanzapine when used over a period of months include weight gain as well as 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.