Women with breast cancer who take both tamoxifen (Nolvadex), an anti-estrogen drug used to treat breast cancer, and the antidepressant paroxetine (Paxil) may increase their risk of dying because Paxil reduces tamoxifen's effectiveness, Canadian researchers report.

"Paxil can deprive women of the benefit of tamoxifen, especially when it is used in combination with tamoxifen for a long time," said lead researcher David Juurlink, MD, PhD, division head of clinical pharmacology and toxicology at Sunnybrook Health Sciences Center in Toronto.

"Patients who are on tamoxifen and who require an antidepressant should probably be given something different," he added.

The report was published in BM), the online edition of the British Medical Journal.

The Study

Dr. Juurlink's group looked at the medical records of 2,430 women with breast cancer who began taking tamoxifen between 1993 and 2005. About 30% of the women were also taking an antidepressant, Paxil being the most common Antidepressants are often prescribed to reduce hot flashes associated with tamoxifen in addition to easing symptoms of depression.

Paxil plus tamoxifen was linked to an increased risk of dying from breast cancer, and the risk increased with the amount of time the drugs were taken together, the researchers found.

Taking Paxil for 41% of the time that tamoxifen was also taken resulted in one extra death from breast cancer within five years of stopping tamoxifen among every 20 women taking the drugs simultaneously, Dr. Juurlink's team estimated. The more time the drugs were taken together, the greater the risk, they added.


Paxil is a selective serotonin reuptake inhibitor (SSRI) that significantly inhibits an enzyme called cytochrome P450 2D6, which is needed to metabolize tamoxifen into its active form. But this dampening effect was not seen with certain other SSRIs evaluated, including citalopram (Celexa) and venlafaxine (Effexor), the researchers said.

SSRIs inhibit 2D6 to varying degrees, the authors said, noting Paxil is exceptionally potent" in that respect.

What To Do

Patients taking Paxil and tamoxifen should talk with their doctors about changing their antidepressant, Dr. Juurlink said. But he advised against abruptly discontinuing Paxil.

There is a very real danger to stopping Paxil suddenly. There is a well-described withdrawal syndrome and the risk of depression becoming more severe," he said.

In addition, any transition to another antidepressant should be done gradually over several weeks, he said.

Expert Commentary

Frank Andersohn, MD, a senior research associate at the Institute for Social Medicine, Epidemiology, and Health Economics at Charité University Medical Center in Berlin, Germany, and author of an accompanying journal editorial, said that "physicians should be aware that paroxetine and other strong 2D6-inhibiting drugs should be avoided in women treated with tamoxifen."

Fluoxetine (Prozac) is also a strong 2D6 inhibitor, the authors noted.

Another expert, Harold J. Burstein, MD, PhD, clinical investigator in the breast oncology center at Dana-Farber Cancer Institute, Brigham and Women's Hospital in Boston, said this paper adds to the substantial literature suggesting that drugs that affect the metabolism of tamoxifen might affect breast cancer outcomes for women taking the drug.

Interpreting The Results

While the results should not alarm patients currently taking SSRIs, they do suggest that patients on tamoxifen who also need SSRIs should probably seek out agents such as Effexor in preference to Prozac or Paxil," said Dr. Burstein.

"The findings are also a reminder that each drug that a patient takes should be thought through carefully," said Dr. Burstein.

Grapefruit May Be Linked

Women who ate the equivalent of half a grapefruit every other day had a 30% increase in breast cancer risk.

Possible reason: The compound in grapefruit that changes blood levels of some drugs also may increase estrogen levels. More research is needed—but women at high risk for breast cancer may want to avoid grapefruit. Other citrus fruits appear to be safe.

Bean that Fights Breast Cancer

Women who ate one-half cup of lentils at least twice a week were 24% less likely to develop breast cancer, compared with women who ate the same amount of lentils less than once a month or not at all.

Theory: Lentils' protective effects may be due to particular types of phytochemicals. One-half cup of lentils has 9 grams (g) of protein, 8 g of fiber, 3 milligrams of iron and only 115 calories. And they are inexpensive. Add lentils while cooking soups and whole grains, and use cooked lentils in salads.

Women with Migraines Have Lower Breast Cancer Risk

Pre- and postmenopausal women who have I a history of migraines have a 26% lower risk for breast cancer. Researchers aren't sure what the connection is, but both migraines and breast cancer are affected by the body's estrogen levels.

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