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Small Study Shows Antidepressants May Interfere with Tamoxifen (dateline May 28, 2004)


The drug tamoxifen  has been shown to be highly effective at treating breast cancer, decreasing the chances of a cancer recurrence, and preventing the disease in women at high risk. However, researchers say that antidepressant drugs, which some women take to help relieve tamoxifen’s side effects, may actually interfere with tamoxifen. In a recent study, the antidepressant drug, Paxil (generic name, paroxetine) disrupted the metabolism of tamoxifen in a small group of women. Further studies are needed to investigate this drug interaction. Given the small size of the study and the fact that antidepressant drugs are very helpful in treating hot flashes, a common side effect of tamoxifen, the researchers do not recommend that women taking tamoxifen stop using antidepressants at this time.

Tamoxifen has been used for two decades to treat breast cancer. More recently, it has also been approved by the U.S. Food and Drug Administration (FDA) for use as a preventive measure in women found to be a high risk for breast cancer. To grow and reproduce, breast cancer cells require the female hormone estrogen. Tamoxifen is an "anti-estrogen" and works by competing with estrogen to bind to estrogen receptors in breast cancer cells. Tamoxifen is formally known as a selective estrogen receptor modulator (SERM). By blocking estrogen in the breast, tamoxifen helps slow the growth and reproduction of breast cancer cells.

In a study of 12 women, David A. Flockhart, M.D., Ph.D. of Indiana University and colleagues found that a by-product of tamoxifen called endoxifen was reduced by 56% in patients while they were taking Paxil and tamoxifen. This affects the metabolism of tamoxifen, though it is unclear whether it alters the effectiveness of the drug.

According to Dr. Flockhart and his team, up to 80% of women who take tamoxifen complain of hot flashes and up to 45% of women label them severe. Therefore, many women are prescribed treatments for hot flashes while on tamoxifen. Antidepressants have been shown to be effective at treating hot flashes.

The researchers say that, because the enzyme that converts tamoxifen to its active form varies in women, the level of endoxifen can vary too. Thus, Paxil may interfere with the metabolism of tamoxifen in some women but not in others. Further studies are needed to better understand this drug interaction.

Right now, there are several questions about tamoxifen and antidepressants left unanswered. Does the interference of Paxil make tamoxifen less effective in some women? Does Paxil increase the risk of a breast cancer recurrence in breast cancer patients on tamoxifen? Do other antidepressants interfere with tamoxifen similarly to Paxil? According to Dr. Flockhart, there is some evidence to suggest that the antidepressant, Effexor (generic name, venlafaxine), does not affect the metabolism of tamoxifen.

Until these questions can be better answered, Dr. Flockhart and colleagues are not advising women on tamoxifen to give up antidepressants if they need them. In addition to helping relieve the hot flashes themselves, antidepressants can improve sleep, sex drive, and overall quality of life in women with hot flashes. Furthermore, antidepressants are frequently used to treat depression, anxiety, or other mood disorders in women on tamoxifen.

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