On Women

Tamoxifen and Antidepressants Don't Mix

By Deborah Kotz

Posted: June 2, 2009

Breast cancer patients have it tough. Besides contending with the disease and its often harrowing treatments, they're also told to avoid certain medications—like hormone therapy for menopausal symptoms—because it could raise their likelihood of having a recurrence. In fact, many breast cancer patients are prescribed antidepressants to combat the hot flashes and mood swings of menopause. Or they're taking the drugs to cope with chronic depression. Unfortunately, these very same mood-lifters also appear to negate the effects of tamoxifen, a lifesaving breast cancer therapy given to women who have tumors that respond to estrogen.

Research presented Sunday at the American Society of Clinical Oncology finds that breast cancer patients taking antidepressants along with tamoxifen were more than twice as likely to have their tumors return after two years, compared with those who were taking tamoxifen alone. The Food and Drug Administration is poised to add a warning to tamoxifen's label alerting doctors to the drug's interaction with antidepressants, according to the Wall Street Journal.

But doctors who are up to date on the latest medical research should already know about this interaction. As early as six years ago, research indicated that tamoxifen was rendered ineffective by antidepressants in the family of selective serotonin reuptake inhibitors (Paxil, Prozac, Celexa, Lexapro, Zoloft). In 2005, oncology researcher Frankie Ann Holmes lamented in a paper published in the Journal of Oncology Practice that doctors still were prescribing Prozac with tamoxifen. "Conversations with colleagues," Holmes wrote, "indicated that this more sophisticated understanding of the peculiar pharmacokinetics of tamoxifen may not have been incorporated into clinical patient care, especially when patients receive medications from other non-oncology physicians."

I'm just wondering what's taken the FDA so long. Why wasn't the tamoxifen label changed years ago?

Breast cancer patients who are on tamoxifen have several options. Postmenopausal women can switch to an aromatase inhibitor, which has the same estrogen-blocking benefits as tamoxifen but doesn't interact with antidepressants. (Aromatase inhibitors aren't approved for use in premenopausal patients.) Women of any age can also switch to a non-SSRI antidepressant like Effexor. Those who aren't putting themselves at risk for a relapse of depression—check with your doctor before stopping an antidepressant—can also try to lift their mood using lifestyle measures like exercise, adequate sunlight, and fish oil. Here are some natural ways to treat depression and what to take for tamoxifen-triggered hot flashes.

Best to check with your doctor or pharmacist, but...

Just because _some_ SSRI antidepressants inhibit CYP2D6, thereby retarding or completely inhibiting the bioactivation of tamoxifen, that doesn't mean that _all_ SSRI antidepressants do.

For example (and this is not exhaustive), Prozac (fluoxetine) and Paxil (paroxetine) are both potent inhibitors of the CYP2D6 drug-metabolizing enzyme. Zoloft (sertraline) is a weaker inhibitor of the enzyme. Finally Celexa (racemic citalopram) and Lexapro (escitalopram) both have much less of an effect on the enzyme. Wellbutrin/Zyban (bupropion) inhibits other CYP450 enzymes, but not (AFAIK) CYP2D6.

Steve Dyer of MA @ Oct 15, 2009 20:31:47 PM

Tamoxifen and Genetics

Tamoxifen works in the body when it converted into its active form called Endoxifen by a liver enzyme called CYP2D6. This enzyme is produced from the CYP2D6 gene on the chromosome. 7-10% of women with breast cancer possess a variant of that gene which results in very low production of the CYP2D6 enzyme.Tamoxifen is hence not converted into endoxifen and it accumulates in the body because it cannot be excreted properly thus causing adverse drug reactions.Women with this gene variant are scientifically called 'poor metabolizers' and are at increased risk of breast cancer recurrance as Tamoxifen does not work for them. Antidepressents which are often given to women to combat side effects such as hot flashes interact with the production of the CYP2D6 enzyme and result in lower than normal levels of the enzyme. Interactions between drugs administered to the patient as well interactions between the drug and the CYP2D6 gene must be carefully analyzed. Companies like Genelex in Seattle offer CYP2D6 testing services known as Tamoxitest, which can help determine the metabolizer status in women.

Sruti Mohandas of PA @ Jul 22, 2009 13:43:07 PM

Pharmacies

I was informed by our mail order pharmacy, Medco, that I should no longer take Wellbutrin with tamoxifen. I immediately informed my oncologist and my OB/Gyn who were grateful, and somewhat humbled, to learn of this fact. My oncologist presented me with a list of antidepressants that did not interact with tamoxifen. I am presently on an SNRI, Pristique, which may help with the hotflshes, but I think my mood swings were better controlled by the Wellbutrin. After taking tamoxifen for 3 more years I may be able to shop around for a better antidepressant or not need one at all. I am very grateful to the pharmacists and Medco for alerting me.

Jane P. of IN @ Jun 15, 2009 17:04:45 PM

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On Women

On Women

Deborah Kotz, senior writer for U.S. News & World Report, covers everything women care about when it comes to their health. She's often tapping out "Oprah-esque" confessions about how the latest news relates to her personally—whether it's on breast cancer, contraception or easing work-family stress. She'd love to hear your confessions too at onwomen@usnews.com. Also, you can follow Deborah on Twitter at twitter.com/debkotz2.

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