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Antidepressants and Tamoxifen May Not Mix

Study Shows Some SSRIs May Cause Breast Cancer Drug to Lose Effectiveness
By
WebMD Health News
Reviewed by Louise Chang, MD

June 1, 2009 (Orlando, Fla.) -- Women who are taking the breast cancer drug tamoxifen should avoid certain antidepressants, researchers say.

That's because a large U.S. study showed that certain selective serotonin reuptake inhibitor (SSRI) antidepressants may prevent tamoxifen from working properly.

In the study, women on tamoxifen who were also taking one of three SSRIs -- Paxil, Prozac, or Zoloft -- were about twice as likely to have their cancer come back, compared with women on tamoxifen who were not taking an SSRI.

SSRIs are prescribed not only to treat the depression that often plagues women with cancer, but also to help relieve hot flashes that can be caused by tamoxifen.

Tamoxifen mixes with a liver enzyme called CYP2D6 in the body to change into the tumor-fighter endoxifen. Many SSRIs block the same enzyme, thus preventing tamoxifen from morphing into its active form.

"We've known that these [drugs] block the activation of tamoxifen chemically, but this is the first time there's evidence that they may be decreasing the effectiveness of their anticancer treatment," says researcher Robert Epstein, MD, chief medical officer at Medco Health Solutions Inc., a pharmacy benefits management company.

Paxil, Prozac, and Zoloft are categorized as moderate-to-potent SSRIs because they are strongest in their ability to block the CYP2D6 enzyme. Celexa, Lexapro, and Luvox are considered weaker SSRIs.

The weaker SSRIs were not linked to an increased risk of breast cancer recurrence, the study showed.

The findings were presented at the annual meeting of the American Society of Clinical Oncology.

A second, Dutch study presented at the meeting found no increased risk of breast cancer coming back in women taking tamoxifen and either weak or strong SSRIs. But the number of women taking both drugs in that study was small -- reason enough for women to err on the side of caution, doctors say.

"There are other options [besides the stronger SSRIs], so why not use them?" says Judy R. Gralow, MD, a breast cancer specialist at the University of Washington in Seattle.

Gralow tells WebMD that if an antidepressant is needed, she recommends her patients take Effexor. "We have a lot of information on Effexor's effectiveness against hot flashes and depression, so that's the one I use," she explains.

Gralow moderated a news conference to discuss the findings of both studies.

Moderate-to-Strong SSRIs

For the U.S. study, Medco researchers mined the company's database of 10.7 million health plan members. They identified about 1,300 women who were prescribed tamoxifen to treat breast cancer between 2003 and 2005.

Of the total, 353 women were also taking moderate-to-strong SSRIs Paxil, Prozac, or Zoloft, 137 were taking weak SSRIs, and the rest were not taking an SSRI.

Over a two-year period, breast cancer came back in 16% of those taking tamoxifen and Paxil, Prozac, or Zoloft, compared with only 7.5% of women on tamoxifen only.

The breast cancer recurrence rate among women taking tamoxifen and the weaker antidepressants Celexa, Lexapro, or Luvox and was similar to that of women taking tamoxifen alone.

For the second study, researchers at Leiden University Medical Center in the Netherlands analyzed information on nearly 2,000 breast cancer patients using tamoxifen, 215 of whom had taken an SSRI.

"In contrast to the previous study, we couldn't find any evidence of an increased risk of breast cancer recurrence" in women taking both drugs, says Vincent O. Dezentje, MD, a trainee in oncology at Leiden University.

Further study is needed to better define the relationship between SSRIs and breast cancer recurrence, he says

In the meantime, "doctors and patients should be cautious about using these drugs together," Dezentje tells WebMD.

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