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| |  Paroxetine Blocks the Beneficial Effects of Tamoxifen in Breast Cancer LONDON -- February 10, 2010 -- Women with breast cancer who take the antidepressant paroxetine at the same time as tamoxifen are at an increased risk of death, concluded a study published in the British Medical Journal. 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 explained. In order for tamoxifen to be effective in the treatment of breast cancer, it must be converted into an active metabolite (endoxifen) by the liver. However, 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 is a potent inhibitor of the metabolic step that converts tamoxifen to endoxifen. David Juurlink, MD, Institute for Clinical Evaluative Sciences (ICES), Toronto, Ontario, and colleagues set out to investigate whether selective serotonin reuptake inhibitors (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. Paroxetine was the most commonly used agent. Results showed 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% of the total time on tamoxifen (the median in this study) will result in 1 additional breast cancer death at 5 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,” said Dr. Juurlink. “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 added. “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.”
SOURCE: British Medical Journal
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