Breast cancer patients taking antidepressant paroxetine at the same time as tamoxifen are at increased risk of death

Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study

Women with breast cancer who take the antidepressant paroxetine at the same time as tamoxifen are at an increased risk of death, concludes a study published on bmj.com today.

However, the authors stress that their results should not lead patients to stop taking tamoxifen, and do not imply that paroxetine itself causes or influences the course of breast cancer. "This is simply a situation in which paroxetine impairs the effectiveness of tamoxifen," they explain.

Breast cancer is the most commonly diagnosed cancer in women worldwide and the drug tamoxifen significantly improves survival. In order to work, however, tamoxifen must be converted into an active metabolite (endoxifen) by the liver.

But some drugs can interfere with this process. Antidepressants are of particular importance because they are commonly used in women with breast cancer, often for long periods of time. Although many antidepressants have little or no impact on tamoxifen's metabolism, paroxetine, a member of the selective serotonin reuptake inhibitor (SSRI) class of drugs, is a potent inhibitor of the metabolic step that converts tamoxifen to endoxifen.

So Dr Catherine Kelly and colleagues at the Institute for Clinical Evaluative Sciences (ICES) in Toronto set out to investigate whether SSRIs can reduce tamoxifen's effectiveness in practice.

They examined the healthcare records of 2,430 women aged 66 years or older with breast cancer who received tamoxifen between 1993 and 2005. About 30% of these women also received an antidepressant at some time during their treatment with tamoxifen, and paroxetine was the most commonly used agent.

The results show that use of paroxetine, but not other SSRIs, in combination with tamoxifen, was associated with an increased long-term risk of breast cancer death, in a fashion that correlated with the extent of drug overlap.

This supports the theory that paroxetine can reduce or abolish the benefit of tamoxifen in women with breast cancer.

The researchers estimate that treatment with paroxetine for 41 percent of the total time on tamoxifen (the median in this study) will result in one additional breast cancer death at five years for every 20 women so treated. The risk with more extensive overlap is greater.

"Our findings indicate that the choice of antidepressant can significantly influence survival in women receiving tamoxifen for breast cancer," says Dr David Juurlink, one of the study's authors and a scientist at ICES. "This observation is consistent with what we know about tamoxifen's metabolism. These results highlight a drug interaction that is extremely common, widely underappreciated and potentially life-threatening, yet uniformly avoidable."

"Tamoxifen is a crucial element of therapy for patients with hormone receptor-positive breast cancer regardless of age or breast cancer stage," he adds. "When co-prescription of tamoxifen with an antidepressant is necessary, preference should be given to antidepressants that exhibit little or no impact on tamoxifen's metabolism."

In an accompanying editorial, Frank Andersohn and Stefan Willich from Charit- University Medical Center in Berlin say that clinicians should avoid co-prescribing paroxetine and tamoxifen in women with breast cancer, but warn against abrupt withdrawal of SSRI treatment.

They also call for this potential interaction to be made clear on all products containing tamoxifen and paroxetine, and for its promotion amongst physicians and pharmacists.