Tamoxifen (or nolvadex) is a drug commonly prescribed to prevent the recurrence of breast cancer, but a common side effect of the treatment is hot flashes. As a result, selective serotonin reuptake inhibitors (SSRIs) - a class of drugs that includes Paxil (paroxetine) and Prozac (fluoxetine hydrochloride) - are commonly prescribed to patients on tamoxifen. These antidepressants have been known to combat the hot flashes along with emotional hardship many women experience after cancer diagnosis and treatment. In fact, some estimate that about one-sixth of women on tamoxifen in the U.S. are taking either Paxil or Prozac along with it.
However, a number of experts have begun to question whether such a combination is the best course of treatment. Their research indicates that women taking an SSRI along with tamoxifen may be more likely to experience a recurrence of their cancer than those who do not.
The problem appears to be that Paxil and Prozac can prevent the liver from converting tamoxifen into its active form, endoxifen, a breakdown product demonstrated to be significant for tamoxifen's beneficial effect on preventing a recurrence of breast cancer. A specific enzyme known as CYP2D6 appears to be critical in this transformation - and SSRIs can block this process. (Dr. Kevin Knopf wrote also about this enzyme; for more, read "Something to Worry About? CYP2D6 and Tamoxifen/Nolvadex Effectiveness.")
Dr. Matthew P. Goetz, an assistant professor of oncology at the Mayo Clinic College of Medicine, has conducted extensive research on the question. He has found that women whose levels of CYP2D6 were suppressed - either because of use of an SSRI or due to an inherited genetic trait - experienced breast cancer recurrence rates much higher than those of other women.
He and fellow researchers determined that the rate of relapse or death in women with suppressed CYP2D6 to be 32 percent, versus just 2 percent for other women. Over 10 years, the rates of recurrence or death grew to 60 percent for the CYP2D6 suppressed women, compared to 20 percent for others.
In a woman taking tamoxifen along with an SSRI, "the levels of the enzyme are the same as a woman born without it," explains Dr. Goetz. "You are essentially suppressing the ability of the body to convert tamoxifen."
In women capable of producing the CYP2D6 enzyme, however, the effect quickly disappears after discontinuing the Paxil or Prozac.
Dr. David A. Flockhart, Chief of the Division of Clinical Pharmacology at the Indiana University School of Medicine, also has serious concerns about the potential for drug interaction for patients taking tamoxifen along with an SSRI. His research on the question in 2003 indicated that women on both drugs appeared to have a lower levels than expected of tamoxifen in their bloodstream.
"Tamoxifen on its own doesn't do anything," says Dr. Flockhart of his findings. "But Paxil blocks the liver's ability to make that breakdown product" that helps prevent breast cancer recurrence.
Despite this research, many oncologists continue to prescribe Paxil or Prozac to alleviate hot flashes for their patients on tamoxifen. They may be unaware the troubling research on this question or believe that these studies need further substantiation. In fact, not all experts are in agreement about the possible consequences of taking tamoxifen and SSRIs. For example, researchers presented data at the 2007 San Antonio Symposium on Breast Cancer and concluded the results "do not support the hypothesis that SSRI modify tamoxifen s effectiveness."
The potential of a tamoxifen/SSRI drug interaction continues to be hotly debated in a variety of forums, such as HealthCentral.com's MyBreastCancerNetwork.com and breastcancer.org. "It's a real concern that is being evaluated," says Dr. Marisa C. Weiss, a practicing oncologist who is the founder and president of breastcancer.org. "No one would want to take a medicine that would interfere with the anticancer effect of the tamoxifen."
Dr. Weiss points out that the potential for drug interaction is a key issue for women who have had breast cancer, many of whom are prescribed dozens of medications to take daily. "Whenever you're taking medicines, you want to make sure the side effects are worth the benefits."
For their part, Dr. Goetz and Dr. Flockhart maintain it is best to prescribe patients on tamoxifen medications other than Paxil or Prozac for hot flashes or depression. Both physicians cite the antidepressant Effexor as a drug that does not seem to inhibit the proper breakdown of tamoxifen.
"It works fine on the hot flashes and doesn't affect the enzyme," says Dr. Flockhart, who notes that yet another commonly used antidepressant, Zoloft, has been linked to similar interactions with tamoxifen as Paxil, although to a lesser extent.
In fact, Dr. Goetz is currently conducting a trial to learn more about the potential interactions between tamoxifen and other drugs. "We are going to study this much more comprehensively."