Q & A: Tamoxifen and Antidepressants

Q: Do certain antidepressants reduce the effectiveness of tamoxifen?

A: A study reported in June at the annual meeting of the American Society of Clinical Oncology suggested that women taking certain antidepressants called SSRIs (selective serotonin reuptake inhibitors) at the same time as the anti-estrogen drug tamoxifen had a higher risk of relapses from their breast cancer when compared to women who took only tamoxifen.

The theory behind the research was that certain antidepressants inhibit CYP2D6, an enzyme in the body that converts tamoxifen into its active, cancer-fighting form. The thinking was that if the enzyme is blocked, then tamoxifen won’t be as effective, leading to earlier relapses from breast cancer. (There have been laboratory experiments that support this concept.)

However, in a similar study presented at the meeting, Dutch researchers found no evidence of an increased relapse rate in women with breast cancer who took tamoxifen and a SSRI simultaneously.

Unlike the Netherlands report, which included more detailed, medical record-based analysis, the U.S. study looked at large numbers of women whose medication histories were kept in a large computer database run by a nationwide pharmacy benefits manager that pays for patients’ prescriptions. Without a detailed analysis linked to actual medical records, the American research should therefore be considered a “signal” that needs further evaluation.

Since antidepressants are widely used in this country both for the treatment of depression and less commonly for menopausal symptoms, such as hot flashes, these reports are bound to raise concern among breast cancer patients.

There is no simple answer as to what a woman with breast cancer should do regarding antidepressant treatment. Clearly, depression is a serious illness that can have grave consequences if not treated properly, and hormone replacement therapy is not an option for treating menopausal symptoms of women with breast cancer.

Ultimately, given the noted research reports, the decision on whether or not to take an SSRI while on tamoxifen is one that you have to make after considering the benefits and risks, and in consultation with your medical oncologist and gynecologist. Most oncologists agree that since not all SSRIs inhibit CYP2D6, women on tamoxifen should only take SSRIs or other antidepressants that are known not to inhibit (or only minimally inhibit) CYP2D6. Understanding the options and alternatives is something that requires careful consideration.

—Len Lichtenfeld, MD, is deputy medical officer for the American Cancer Society