Use of a selective serotonin reuptake inhibitor (SSRI) is common in women taking tamoxifen (Nolvadex, and others) for breast cancer, both to treat depression and to decrease hot flashes. However, tamoxifen must be metabolized by CYP2D6 to become pharmacologically fully active (MJ Higgins et al. J Natl Compr Canc Netw 2009; 7:203), and the SSRIs fluoxetine (Prozac, and others) and paroxetine (Paxil, and others) are strong inhibitors of CYP2D6. Sertraline (Zoloft, and others) inhibits CYP2D6 to a lesser extent. Citalopram (Celexa, and others) and escitalopram (Lexapro), the 2 other SSRIs approved for treatment of depression, are only weak inhibitors of CYP2D6.

Two observational studies presented at a recent meeting of the American Society of Clinical Oncology (45th annual meeting, May 29-June 2, 2009, Orlando, FL abstracts CRA508, CRA509) examined the effect of strong inhibitors of CYP2D6 on the success rate of tamoxifen in preventing recurrence of breast cancer. One found that women who took fluoxetine, paroxetine or sertraline (or bupropion, duloxetine, terbinafine, quinidine or long-term diphenhydramine) with tamoxifen had a higher 2-year recurrence rate (13.9% vs. 7.5%). The other study found no association between cancer recurrence and use of a CYP2D6 inhibitor.

There is no good evidence that any one SSRI is more effective than any other for treatment of depression. For women who are taking tamoxifen and need to begin treatment with an SSRI to treat depression, citalopram or escitalopram might be the safest choice (Treat Guidel Med Lett 2006; 4:35). Use of an SSRI to treat hot flashes in women taking tamoxifen should probably be reconsidered.