Harvard Women's Health Watch

In the journals: Some antidepressants interfere with tamoxifen more than others

Tamoxifen (Nolvadex) is a selective estrogen receptor modulator, or SERM. It's commonly prescribed after surgery for early-stage estrogen receptor–positive breast cancer — that is, breast cancer that's fueled by estrogen. By blocking estrogen's activity in breast cells, tamoxifen reduces the risk of recurrence as much as 50%. For women at high risk, it reduces the likelihood of developing a first breast cancer by the same amount.

Unfortunately, not all women taking tamoxifen get its full benefit. Tamoxifen is converted in the body to its active form, endoxifen, by a member of the P450 family of enzymes called CYP2D6. Some women have a mutation in the gene that synthesizes CYP2D6 and may not metabolize tamoxifen as effectively as women with a normal gene.

Another problem is that several selective serotonin reuptake inhibitors and other antidepressants can inhibit CYP2D6, lowering blood concentrations of tamoxifen in women who might otherwise benefit from the drug. Today, about 500,000 women in the United States are taking tamoxifen, and as many as 30% of them also take an antidepressant — for emotional distress, tamoxifen-induced hot flashes, or both. The concern is that the combination may put some of these women at increased risk for breast cancer recurrence.

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