The specific serotonin reuptake inhibitors sertraline and fluoxetine promote tumor growth in a mouse xenograft model of cholangiocarcinoma

Abstract

Cholangiocarcinoma is an aggressive cancer of the bile ducts with limited treatment options and a high mortality rate. Patients with cancer have over a twofold higher rate of depression than the general population and are prescribed selective serotonin reuptake inhibitors (SSRIs) to manage their depression. However, serotonin has been demonstrated to promote the proliferation of cancer cells. In this mouse xenograft study, we provide evidence that the SSRIs sertraline and fluoxetine lead to increased serotonin bioavailability that results in a proliferation of cholangiocarcinoma cells. Cholangiocar-cinoma cell proliferation was not observed in vitro, indicating that the effects of SSRIs are due to increased serotonin levels in noncancerous cells of the body. These novel findings on the effect of SSRIs in promoting the growth of cholangiocarcinoma support the notion that these antidepressants should be used cautiously in this patient population.