Fluoxetine Treatment Comprises the Antiemetic Efficacy of Ondansetron in Cancer Patients

Fluoxetine (Prozac) is an effective and increasingly widely used antidepressant. It is a 5-hydroxytryptamine (5-HT) re-uptake inhibitor. It produces its pharmacological effects by preventing the elimination of the 5-HT produced at nerve synapses, thus increasing its concentration at that location. Ondansetron (Zofran), is a 5-HT3 antagonist, which produces its pharmacological effect by competing with 5-HT receptors at the synapse. When both fluoxetine and ondansetron are used together, there is the possibility that the accumulation of 5-HT resulting from the use of fluoxetine may compete with ondansetron at the receptors, potentially reducing the antiemetic effects of ondansetron. Clinically, this has been observed in three patients treated with both compounds at the same time, while they were receiving carboplatin combination chemotherapy. The possibility that concurrent administration of the 5-HT re-uptake inhibitors, fluoxetine, may reduce the antemetic effectiveness of ondansetron is relevant to the established role of antidepressants in the management of patients with malignant disease, in whom the prevention of emesis is also important. Further investigation of this possible interaction is recommended.