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Paroxetine blocks effect of tamoxifen on breast cancer

Clinical Question:
Do selective serotonin reuptake inhibitors antagonize the effect of tamoxifen in patients with breast cancer?

Bottom Line:
Women who take tamoxifen (Nolvadex) for the treatment of breast cancer should not be given paroxetine (Paxil) at the same time. Women who take both drugs are at increased risk of overall mortality and breast cancer-related mortality as compared with women are not taking a selective serotonin reuptake inhibitor (SSRI) or are taking an SSRI other than paroxetine. (LOE = 1b)

Reference:
Kelly CM, Juurlink DN, Gomes T, et al. Selective serotonin inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study. BMJ 2010;340:c693.  [PMID:20142325]

Study Design:
Cohort (retrospective)

Setting:
Population-based

Synopsis:
This study investigated the possibility that SSRIs may have an adverse effect on outcomes in women treated with tamoxifen for breast cancer through inhibition of the metabolism of tamoxifen to its active metabolite. These Canadian investigators identified all women in Ontario, Canada with breast cancer, older than 66 years, who were started on tamoxifen between 1993 and 2005 and were co-prescribed a single SSRI during their treatment. These women were followed up until their death or the end of the study.. Of the 2430 women treated with tamoxifen and a single SSRI, 15.4% died of breast cancer during follow-up. After adjusting for age, duration of tamoxifen use, and other factors, there was a time-related increase in breast cancer-related deaths, as well as overall mortality, in patients who also took paroxetine. In other words, the longer the women took paroxetine with tamoxifen, the more likely they were to die of breast cancer. There was no increased risk associated with the use of other SSRI antidepressants. For women who took paroxetine 41% of the time they were also taking tamoxifen -- which was the median duration of overlap in the study -- one additional woman would die of breast cancer for every 20 women taking the combination instead of another antidepressant (number needed to treat to harm= 19.7; 95% CI 12.5-46.3). If paroxetine is used the entire duration of tamoxifen use, one additional woman would die of breast cancer for every 7 women taking the combination instead of another antidepressant (NNTH = 6.9, 95% CI 4.3-18.6)

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