Antidepressants supress Tamoxifen's Value

Tamoxifen's Effect May Be Muted by Hot Flash Meds

But experts say it's no reason to stop taking the breast cancer drug

By Kathleen Doheny

HealthDay Reporter

New research shows the effectiveness of tamoxifen, a drug that fights breast cancer and its return, may be hampered by the antidepressant often prescribed along with it to cool the hot flashes it can cause.

However, that's no reason to stop taking tamoxifen, cautions study author Dr. David Flockhart, director of the Division of Clinical Pharmacology at the Indiana University School of Medicine. The report appears in the Dec. 3 issue of the Journal of the National Cancer Institute.

"Tamoxifen is a very important drug, and we don't think women should stop taking it because of this," he stresses.

The drug that Flockhart looked at is a newer antidepressant, paroxetine (Paxil), which is often prescribed for women on tamoxifen to ease the hot flashes that can accompany its use. He evaluated 12 women with a history of breast cancer but no current evidence of the disease who took tamoxifen and paroxetine.

He found there was a substantial decrease in blood levels of a metabolite, or breakdown product, of tamoxifen after treatment with the antidepressant. That meant lower levels of tamoxifen were available in the bloodstream.

The metabolite that was in shorter supply is a newly discovered one, which the researchers dubbed endoxifen. The concentration of this metabolite was reduced from 24 percent to 64 percent, with a mean decrease of 56 percent. This variation, Flockhart speculates, may be one reason tamoxifen is more effective in some patients than in others. The genetic makeup of a person can also affect the drug's effectiveness, he adds.

Paroxetine, as well as some other antidepressants, along with tamoxifen, are metabolized through a shared pathway, Flockhart explains.

The discovery "provides a lot more understanding of how the drug works to scientists. It also provides the basis for understanding drug interactions with tamoxifen," Flockhart says.

Tamoxifen belongs to the general group of drugs known as hormone antagonists. It is used to prevent breast cancer in women at high risk, to decrease the risk of getting invasive breast cancer in women with localized cancer and to prevent cancer from coming back after treatment for breast cancer, according to the American Cancer Society.

However, a side effect is hot flashes, and antidepressants are often prescribed because they can reduce hot flashes. Up to 80 percent of women who take tamoxifen complain of hot flashes, says Flockhart, and up to 45 percent of women rate them as severe.

"It's an eye-opener, actually," says Dr. Herman Kattlove, a spokesman for the American Cancer Society. Women should take the new study into account, he advises, when balancing the benefits and risks of therapy.

"I think it's important to be aware of it," Kattlove says. "Judge the small risk that [antidepressants prescribed for hot flash relief] might affect the way the tamoxifen works."

The standard tamoxifen regimen, he says, is five years.

December 2, 2003

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