A new study has reported that paroxetine (Paxil) reduces the effectiveness of tamoxifen when both are taken concurrently. The study was designed to determine whether some selective serotonin reuptake inhibitors (SSRIs) interfere with tamoxifen’s effectiveness by blocking its activation by cytochrome P450 2D6 (CYP2D6). Variations in the cytochrome P450 2D6 (CYP2D6) gene have been shown to influence interindividual variability in drug metabolism and efficiency. P450 2D6 is needed to metabolize tamoxifen into its active form. The study involved a review of the medical records of 2,430 female breast cancer survivors aged at least 66 years and living in Ontario. Subjects had been treated with tamoxifen between 1993 and 2005. Approximately 30% of the women also had an overlapping period of treatment with a single SSRI. In addition to their traditional use in treating depression, antidepressants are sometimes prescribed to treat hot flashes associated with tamoxifen use. The main study outcome was risk of death from breast cancer after completion of tamoxifen treatment based on the proportion of time during which an SSRI had been co-prescribed.
During an average follow-up period of 2.38 years, 374 (15.4%) of the women died from breast cancer. Increases in the proportion of time on tamoxifen with overlapping use of Paxil, an irreversible inhibitor of CYP2D6, were found to be associated with increases in the risk of death from breast cancer. No increases in risk of death from breast cancer were observed for the antidepressants citalopram (Celexa) and venlafaxine (Effexor). However, the authors noted that Fluoxetine (Prozac) is also a strong P450 2D6 inhibitor and probably should also be avoided. The authors estimate that concurrent use of Paxil for 41% of the tamoxifen treatment period would result in one additional death from breast cancer within five years of the end of tamoxifen treatment for every 20 patients so treated. The risk of breast cancer death for longer periods of overlap would be higher. The authors conclude that Paxil appears to reduce or abolish the benefit of tamoxifen in breast cancer survivors.
Certain other drugs, supplements and foods also reduce tamoxifen effectiveness
This study confirms previous findings that Paxil and Prozac can interfere with the effectiveness of tamoxifen. The following foods (or their major components), supplements, and drugs have also been found to reduce the effectiveness of tamoxifen and should be avoided during treatment:
Hormone replacement therapy, including bioidentical or natural hormones
Vitamin E supplements
Please see the tamoxifen web page for a list of foods that can enhance the effectiveness of tamoxifen or reduce its side effects.