Do Antidepressants Interfere With Tamoxifen? Results Unclear

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One of two studies suggests that women who take the hormonal therapy medicine tamoxifen at the same time as one of two common antidepressant medicines: Prozac (chemical name: fluoxetine) or Paxil (chemical name: paroxitene), may not get the full benefits of tamoxifen. The results were presented at the 2009 American Society of Clinical Oncology (ASCO) annual meeting.

Tamoxifen is used to:

  • Lower the risk of developing a first time hormone-receptor-positive breast cancer in pre- and postmenopausal women with higher-than-average risk.
  • Lower the risk of breast cancer coming back (recurrence) in women diagnosed with early-stage, hormone-receptor positive breast cancer.

An enzyme called CYP2D6 helps tamoxifen work in the body. Other research has shown that women with an abnormal gene that blocks their bodies' ability to produce CYP2D6 don't get the same risk-reduction benefits from tamoxifen as women who produce CYP2D6. So researchers wondered if medicines that block production of CYP2D6 could reduce tamoxifen's benefits.

The antidepressants Prozac and Paxil are selective serotonin reuptake inhibitors (SSRIs). Prozac and Paxil are used to ease symptoms of depression, but they also can be used to manage hot flashes, which can be a side effect of tamoxifen. Both Prozac and Paxil block CYP2D6 production -- medicines that do this are called CYP2D6 inhibitors. Not all SSRIs are CYP2D6 inhibitors. Also, other medicines besides SSRIs are CYP2D6 inhibitors.

In a U.S. study, doctors looked at breast cancer recurrence in nearly 1,300 women who were taking tamoxifen to lower their risk of breast cancer coming back. While most of the women weren't taking a CYP2D6 inhibitor, 353 were taking a CYP2D6 inhibitor while taking tamoxifen. Breast cancer was almost twice as likely to come back in the women taking a CYP2D6 inhibitor at the same time as tamoxifen in the 2 years after starting tamoxifen compared to women who weren't taking a CYP2D6 inhibitor:

  • 13.9% of women taking tamoxifen AND a CYP2D6 inhibitor had breast cancer come back
  • 7.5% of women taking tamoxifen alone had breast cancer come back

A similar study was done in the Netherlands. But the Dutch study found no difference in the risk of recurrence between women who took tamoxifen with a CYP2D6 inhibitor and women who took tamoxifen and didn't take a CYP2D6 inhibitor:

  • 13.3% of women taking tamoxifen and a CYP2D6 inhibitor had breast cancer come back
  • 14.6% of women taking tamoxifen alone (or who took a CYP2D6 inhibitor for fewer than 60 days) had breast cancer come back

Because of the different results, more research is needed before doctors can say for sure that taking a CYP2D6 inhibitor reduces the benefits of tamoxifen. Still, the findings from the U.S. study suggest that women taking tamoxifen might want to consider medicines that aren't CYP2D6 inhibitors to manage hot flashes.

If you're taking tamoxifen, tell your doctor about ALL other medicines you take, including vitamins and supplements. Your doctor can tell you if any of your other medications are CYP2D6 inhibitors. If they are, ask your doctor if you should change your treatment plan based on this latest information. If you're taking Prozac or Paxil, your doctor may consider switching you to a different antidepressant. Your doctor also may recommend that you switch to a different hormonal therapy medicine, such as an aromatase inhibitor, that isn't affected by CYP2D6 inhibitors. Aromatase inhibitors can be a good alternative to tamoxifen for postmenopausal women. Aromatase inhibitors aren't recommended for premenopausal women.

If you're not currently taking tamoxifen but hormonal therapy will be part of your treatment plan, review all other medicines you're taking with your doctor. If any of your medicines are CYP2D6 inhibitors, your doctor will take that into consideration when deciding on a hormonal therapy medicine.

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