Common antidepressants lower effects of tamoxifen in many women

INDIANAPOLIS - Additional evidence that a class of antidepressants can reduce the effectiveness of tamoxifen has been published by researchers from the Indiana University School of Medicine, the University of Michigan and Johns Hopkins University.

Results of the trial are published in the January 5 issue of the Journal of the National Cancer Institute.

The large clinical trial confirmed data from an earlier study showing that selective serotonin reuptake inhibitor antidepressants may hinder the effectiveness of tamoxifen, a drug commonly administered to breast cancer patients. The study also reports that researchers now have pinpointed genetic types that are linked with this effect.

Led by David Flockhart, M.D., Ph.D., an IU professor of medicine and director of the Division of Clinical Pharmacology, the researchers examined the effects of SSRIs in women who were prescribed tamoxifen to treat the common side effects of breast cancer therapy which include depression and hot flashes.

More than a fourth of the women enrolled in this study were prescribed SSRIs. The study showed that the various SSRIs taken by the women have different effects on the amount of active tamoxifen byproducts in their blood.

"This is important because previous studies have shown that when tamoxifen is broken down, the resulting molecules are extremely powerful at blocking estrogen receptors and thereby exert a cancer-inhibitive effect," said Dr. Flockhart.

"We have withheld clinical recommendations, because at this point we don't have final data," said Dr. Flockhart. The study makes clear that knowledge of a drug's ability to inhibit CYP2D6 enzyme activity may help clinicians anticipate important drug interactions. Genetic testing may help identify a group of women who may experience greater benefit from tamoxifen or those who may benefit more from one SSRI than another, he said.

This study is the first large-scale clinical trial to determine the influence of multiple genetic variations and drug interactions on the plasma concentrations of tamoxifen and its active metabolites.

"We can see the light at the end of the tunnel," said Dr. Flockhart. "Using our pharmacogenetic tool kit, we are very close to being able to identify which women should be given which drug to treat her depression or hot flashes."

This study was funded by the Pharmacogenetics Research Network of the National Institutes of Health.

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