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After 5 Years on Tamoxifen and Zoloft – Do I Have to Take Tamoxifen Again?


Updated November 12, 2011

Written or reviewed by a board-certified physician. See About.com's Medical Review Board.

Tamoxifen, Zoloft, Effexor

Tamoxifen, Zoloft, Effexor

Photo © Pam Stephan
Question: After 5 Years on Tamoxifen and Zoloft – Do I Have to Take Tamoxifen Again?
I took tamoxifen and Zoloft for 5 years after my breast cancer treatments. My hot flashes were terrible without Zoloft. Now I find out that some SSRIs wipe out the benefits of Tamoxifen! Do I have to take tamoxifen or an aromatase inhibitor for another 5 years to prevent a recurrence?-- About.com Breast Cancer Forum Member

That's a good, practical question - and one that affects many breast cancer survivors. The menopausal symptoms brought on by chemotherapy and tamoxifen are often treated with medications called selective serotonin reuptake inhibitors (SSRIS), known more commonly as antidepressants, and the SSRI Zoloft has been a popular drug of choice. At low doses, these drugs can be great for managing hot flash symptoms. But now we know that several SSRIs -- including Zoloft -- actually block the cytochrome P450 enzyme (CYP2D6) that converts tamoxifen into endoxifen, the substance that provides your anti-estrogen benefit. Put simply, Zoloft moderates your hot flashes because it reduces the power of tamoxifen. And that also means that you get less of the anti-estrogen benefit that helps reduce your risk of breast cancer recurrence.

Expert Opinion on Tamoxifen and Zoloft

For an expert opinion, I reached out to Dr. Nancy Vander Velde, an educator and researcher at Tulane University School of Medicine. Dr. Vander Velde has looked over the studies on tamoxifen and Zoloft, and considered the results. "Overall, these studies are reassuring for most breast cancer patients who have taken SSRI antidepressants while on tamoxifen," she said. That's because research does not prove that your survival or recurrence rates will be worse after taking tamoxifen with Zoloft. Research has not clearly shown why this drug combination doesn't affect your cancer outcome.

Is More Tamoxifen Better?

You may be wondering if you'll need to take tamoxifen for another five years, to get the full benefit of the drug. According to Dr. Vander Velde, "Five years is the optimal time for tamoxifen therapy, and longer duration does not have benefits." So if you've already taken this drug for the recommended five years, you are likely done. However, there is some research that indicates that some women benefit from an additional five years of therapy (regardless of Zoloft use) so definitely reach out to your doctor for more information.

Tamoxifen Resistance Testing

Zoloft isn't the only thing that can prevent tamoxifen from working well. If you have a variation of the CYP2D6 gene, your liver may not efficiently convert tamoxifen into endoxifen. This is called tamoxifen resistance. However, research is conflicting, as some studies show that even "poor metabolizers" still process the drug enough to see a benefit from it.

If you are concerned about tamoxifen resistance, you may want to try a new genetic test. A simple cheek swab is all you have to provide to have your DNA tested for the CYP2D6 genetic variation. Because this test is so new and undergoing research, it is not a definitive test that will predict absolutely whether or not you are tamoxifen resistant. Again, its benefit is unknown.

And, Dr. Vander Velde says that for women who have already taken tamoxifen for five years, there's no point in having this test.

You Have Options for SSRIs

Let's suppose you've taken tamoxifen for just a year or two. Your SSRI may be Zoloft or Paxil. Now that you know those combinations aren't entirely safe for you, consider a change of therapy. "If a woman is currently on tamoxifen and needs an antidepressant, I would recommend using antidepressants in another drug class. If an SSRI seems to be the best option, I would suggest using mild inhibitors such as citalopram (Celexa) or duloxetine (Cymbalta) as opposed to more potent inhibitors such as paroxetine (Paxil)," said Dr. Vander Velde. A study done in Denmark in 2010 showed that venlafaxine (Effexor) has no reported ill effects on the benefits of tamoxifen. Additionally, a newer SSRI known as Pristiq might be a good option, as well as a drug called gabapentin, which is often used to treat seizures, but also helps regulate other body processes.


Breast cancer recurrence risk related to concurrent use of SSRI antidepressants and tamoxifen. Lash TL, Cronin-Fenton D, Ahern TP, Rosenberg CL, Lunetta KL, Silliman RA, Hamilton-Dutoit S, Garne JP, Ewertz M, Sørensen HT, Pedersen L.  Acta Oncol. 2010;49(3):305.

Effect of concomitant CYP2D6 inhibitor use and tamoxifen adherence on breast cancer recurrence in early-stage breast cancer. Dezentjé VO, van Blijderveen NJ, Gelderblom H, Putter H, van Herk-Sukel MP, Casparie MK, Egberts AC, Nortier JW, Guchelaar HJ.  J Clin Oncol. 2010;28(14):2423.

Five versus more than five years of tamoxifen for lymph node-negative breast cancer: updated findings from the National Surgical Adjuvant Breast and Bowel Project B-14 randomized trial.  Fisher B, Dignam J, Bryant J, Wolmark N.  J Natl Cancer Inst. 2001;93(9):684.

Nancy Vander Velde MD, Assistant Professor of Medicine, Tulane University School of Medicine, Section of Hematology Oncology.  Personal correspondence on October 7, 2011.

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