Antidepressants Often Prescribed with Tamoxifen can Double Risk of Breast Cancer Recurrence

A new retrospective study shows that use of three widely prescribed selective serotinin reuptake inhibitors (SSRIs)—Prozac (fluxetine), Paxil (paroxetine), and Zoloft (sertraline)—more than double the risk of breast cancer recurrence in women treated with tamoxifen. These drugs, which are considered moderate to potent CYP2D6 inhibitors, block the activation of tamoxifen chemically, reducing the efficacy of this drug. In contrast, SSRIs considered to be weak CYP2D6 inhibitors, such as Celexa (citalopram), Lexapro (escitalopram), and Luvox (fluvoxamine), were not found to increase the risk of recurrent breast cancer when used concomitantly with tamoxifen.

The study included approximately 1,300 women who were newly prescribed tamoxifen between 2003 and 2005 to treat breast cancer. All patients were monitored for at least 2 years (mean, 2.7 years) and had to be at least 70% compliant with their tamoxifen therapy. On average, patients used tamoxifen and one CYP2D6 concurrently for 340 days.

Initially, the analysis examined two different cohorts: the first included 353 women (27% of patients) who were taking a moderate to potent CYP2D6 inhibitor (this was not limited to antidepressants) in conjunction with tamoxifen and then 945 women on tamoxifen who were not taking any CYP2D6 inhibitors. When examining the patients' medical and pharmacy records, those women receiving a moderate to potent CYP2D6 inhibitor had a breast cancer recurrence rate of 13.9% at 2 years versus a rate of 7.5% in those receiving only tamoxifen.

When researchers examined only the subset of women taking CYP2D6 inhibitors and compared those on moderate to potent inhibitors (n = 213) with those on weak inhibitors (n = 137), they found that the risk for recurrence almost doubled between the cohorts, with those on moderate to potent CYP2D6 inhibitors having a breast cancer recurrence rate of 16% and those on weak CYP2D6 inhibitors having a rate of 8.8%.

Because almost 30% of women on tamoxifen are also on antidepressants, oncologists need to know which antidepressants their patients are on to ensure that the efficacy of tamoxifen is not compromised. According to Robert Epstein, MD, one of the study researchers and chief medical officer at Medco, which funded the study, “the choice of which SSRI is prescribed could make a huge difference in whether there's a recurrence of the disease. That's very important information for breast cancer patients and their physicians.”