Women who took GlaxoSmithKline's Paxil while taking tamoxifen at the same time were more likely to die of their breast cancer, the researchers found. The longer the overlap between Paxil and tamoxifen, the more likely the patients were to die, they reported in the British Medical Journal.

It is likely because Paxil, sold generically as paroxetine, interferes with the compound the body uses to process tamoxifen, the researchers said.

There is probably a better choice of antidepressants for women taking tamoxifen but (any change) should be done gradually with a doctor, said Dr. David Juurlink of the Institute for Clinical Evaluative Sciences and Sunnybrook Health Sciences Center in Toronto.

It is easy for women on tamoxifen to become alarmed by the results of this study, Juurlink added in a telephone interview.

People shouldn't be stopping their tamoxifen. It is an extremely important medication. And he said no-one should immediately stop taking paroxetine either without first consulting a doctor because suddenly stopping an anti-depressant can be dangerous.

Juurlink and colleagues looked at the healthcare records of 2,430 breast cancer patients 66 or older who took tamoxifen between 1993 and 2005. About 30 percent of the patients also took an antidepressant at some time during their treatment with tamoxifen, and paroxetine was the most common one.

Fifteen percent of the patients died of breast cancer during the study.

After other factors were taken into the account, the researchers found that women who took Paxil and tamoxifen together for a quarter of the treatment time were 25 percent more likely to die of breast cancer.

This rose to a 91 percent risk for the women who took tamoxifen and Paxil together for 75 percent of the time.

In contrast, no such risk was seen with other antidepressants, the researchers wrote.

Tamoxifen can reduce the risk of breast cancer returning by 50 percent if women take it for five years, although the drug is often being replaced with a newer class of drugs called aromatase inhibitors.

For the body to use it, tamoxifen must be broken down by an enzyme called CYP2D6.

A class of antidepressants called selective serotonin reuptake inhibitors or SSRIs can interfere with CYP2D6.

Paxil is a fairly potent inhibitor of that enzyme, Juurlink said. So is fluoxetine, the first SSRI antidepressant.

His team did not find that fluoxetine, sold under the brand name Prozac, had the same effect, but it could be because so few women took that particular antidepressant, he said.

These results highlight a drug interaction that is extremely common, widely underappreciated and potentially life-threatening, yet uniformly avoidable, Juurlink said.

Glaxosmithkline Medicine Cancer