Although antidepressants can help women taking tamoxifen avoid some unpleasant side effects, a new study raises the possibility that at least one of these drugs may also cause them to lose some of the benefits. Researchers have found that paroxetine (Paxil) can interfere with the metabolism of tamoxifen. Their report appears in the Journal of the National Cancer Institute (Vol. 95, No. 23: 1758-1764).

Only 12 women took part in the study. A larger study is needed, researchers caution, before it's known whether women should stop combining tamoxifen and antidepressants. For now, treatment recommendations should not change, they say.

"Women should absolutely not stop taking tamoxifen," said lead researcher David Flockhart, MD, PhD, of the Indiana University School of Medicine. "It's an important drug and we don't think this compromises its reputation."

Not only can tamoxifen shrink breast cancers, it can also prevent them from developing in high-risk women. And for many years, women who have had surgery for breast cancer have been put on the drug for 5 years afterward to prevent the cancer from coming back.

Nevertheless, tamoxifen does have some side effects. As many as 80% of women who take the drug get hot flashes, and 45% rate them as severe. Recently, doctors have found that SSRI (selective serotonin reuptake inhibitor) antidepressants such as Prozac (fluoxetine), Paxil (paroxetine), and Effexor (venlafaxine) can reduce the severity and frequency of these hot flashes.

Using both types of drugs together, though, may be a problem because of the way each drug works. Before tamoxifen can have an effect on breast cancer cells, the body must convert it (metabolize it) into an active substance. SSRI antidepressants are metabolized by the same pathway as tamoxifen, causing researchers to worry that the SSRIs might hinder tamoxifen's conversion.

The researchers studied 12 breast cancer survivors who were taking tamoxifen to prevent a recurrence and were having troublesome hot flashes. They were all given Paxil for four weeks. The researchers examined blood samples taken before Paxil was given and after 4 weeks of taking both drugs.

They found that one important anticancer by-product of tamoxifen, a compound named endoxifen, was lowered by an average of 56% during the month on Paxil. Other compounds were unaffected.

Because the enzyme responsible for converting tamoxifen to its active form varies among individuals, endoxifen was found to be lower in some women than in others. This means that some, but not all, women may metabolize tamoxifen abnormally if they also take antidepressants.

Flockhart said only about 7% of women have the particular genetic mutations that would cause them to have the lowest concentrations of tamoxifen by-products.

The researchers are quick to point out that they don’t know if this impact on metabolism will actually cause tamoxifen to be less effective.

"We don't know what effects it has on [breast cancer] recurrence," Flockhart said. More studies are under way, but they will take years to complete.

More research is also needed to determine if SSRIs other than Paxil will have the same effect on tamoxifen's metabolism. There is data to suggest that venlafaxine (Effexor) does not interfere with tamoxifen, Flockhart said.

Women who are concerned about combining antidepressants with tamoxifen should talk to their doctor about the possibility of switching to venlafaxine, Flockhart said.