Antidepressants may reduce tamoxifen's benefits

Antidepressants used to treat hot flashes in women taking the breast cancer drug tamoxifen may reduce the effectiveness of the tumor-fighting medication, U.S. doctors said on Tuesday. Their study, published in the Journal of the National Cancer Institute, also offered a possible explanation for why tamoxifen works better in some women than others. "Our study suggests that tamoxifen's metabolism, and possibly its effectiveness, can be modified by the genetic makeup of the person taking the drug and by the use of another drug prescribed to reduce tamoxifen-related hot flashes," said David Flockhart of the Indiana University School of Medicine, who led the study. Tamoxifen is widely used to treat breast cancer and to prevent the disease in women at high risk of developing it. Some studies have shown that lesbians are at a higher risk for breast cancer than heterosexual women. Up to 80% of women taking tamoxifen, which helps block the effects of the hormone estrogen, experience hot flashes as a side effect. Antidepressants in a class called selective serotonin reuptake inhibitors are often used to treat the hot flashes. Flockhart's team tested the SSRI Paxil. SSRI drugs are known to interfere with the enzyme that breaks down tamoxifen into active anticancer agents called metabolites, including 4-hydroxy-tamoxifen, believed to be tamoxifen's most active breakdown product. Looking at the study subjects' blood, the researchers discovered a previously unknown metabolite they named endoxifen that also appears to have significant anticancer activity. However, in the women taking Paxil, endoxifen concentrations fell anywhere between 24% and 64% when compared with levels in women not taking the antidepressant. The study included only 12 women, so more research is needed to show whether taking antidepressants reduces the benefits of taking tamoxifen, the researchers concluded.