Taking Antidepressant with Tamoxifen Reduces Tamoxifen’s Effectiveness

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A study found that women taking the antidepressant Paxil (chemical name: paroxitene) at the same time as the hormonal therapy medicine tamoxifen were more likely to die from breast cancer than women taking tamoxifen who never took Paxil.

This result is similar to results from other research and suggests that Paxil interferes with tamoxifen's ability to treat breast cancer.

Tamoxifen is used to:

  • reduce breast cancer risk in women who haven't been diagnosed but are at higher-than-average risk for disease
  • lower the risk of breast cancer coming back (recurrence) in women diagnosed with early-stage, hormone-receptor-positive breast cancer
  • treat advanced-stage hormone-receptor-positive breast cancer

An enzyme called CYP2D6 helps tamoxifen work in the body. Some research has shown that women with an abnormal gene that blocks their bodies' ability to produce CYP2D6 don't get the same benefits from tamoxifen as women who produce CYP2D6.

Earlier research has shown that some medicines interfere with how CYP2D6 works, which reduces tamoxifen's effectiveness against breast cancer. These medicines include some antidepressants known as serotonin-specific reuptake inhibitors (SSRIs) -- including Paxil -- and serotonin-norepinephrine reuptake inhibitors (SNRIs). These antidepressant medicines are sometimes used to ease symptoms of depression or to manage hot flashes that can be a side effect of hormonal therapy in women being treated for breast cancer. Some other widely used medicines:

  • Cardioquin (chemical name: quinidine)
  • Benadryl (chemical name: diphenhydramine)
  • Tagamet (chemical name: cimetidine)

can block CYP2D6.

In this very large study, researchers looked at the medical records of more than 24,000 postmenopausal women diagnosed with hormone-receptor-positive breast cancer from 1993 to 2005. All the women were treated with tamoxifen and 7,500 of the women also took one or more of the following antidepressant medicines for some period of time while taking tamoxifen:

  • Paxil
  • Zoloft (chemical name: sertraline)
  • Celexa (chemical name: citalopram)
  • Effexor (chemical name: venlafaxine)
  • Prozac (chemical name: fluoxetine hydrochloride)
  • Luvox (chemical name: fluvoxamine)

All of these are SSRI antidepressants except Effexor, which is an SNRI.

The researchers followed the women for about 2.4 years, comparing the outcomes of women who took an antidepressant to the outcomes of women who didn't. The researchers narrowed the study to compare the 2,430 women who took only one antidepressant while on tamoxifen to women who didn't take an antidepressant.

Most of the women who took only one antidepressant took Paxil (25.9%), followed by Zoloft (22.3%), Celexa (19.2%), Effexor (15%), Prozac (10.4%), and Luvox (7.2%).

Women who took Paxil for some period of time while taking tamoxifen were up to 91% more likely to die from breast cancer during the follow-up period compared to women who didn't take an antidepressant while taking tamoxifen. The increased risk of dying from breast cancer was different depending on how long a woman took Paxil and tamoxifen at the same time (called "therapeutic overlap"). Compared to women who never took Paxil, the likelihood of dying from breast cancer was:

  • 24% higher in women who took Paxil one-quarter of the time they were taking tamoxifen
  • 54% higher in women who took Paxil half the time they were taking tamoxifen
  • 91% higher in women who took Paxil three-quarters or more of the time they were taking tamoxifen

Women who took an antidepressant other than Paxil had the same risk of dying from breast cancer as women who never took an antidepressant.

Still, other research has shown that Prozac, an SSRI, also strongly interferes with the CYP2D6 enzyme and decreases the benefits of tamoxifen.

The researchers think that Paxil's negative effects on tamoxifen were so strong in this study because Paxil's effect on the CYP2D6 enzyme is permanent (called "irreversible inhibition"). Other SSRI antidepressants do not inhibit the enzyme permanently.

If you're taking tamoxifen, tell your doctor about ALL other medicines you take, including vitamins, supplements, and over-the-counter medications. Your doctor can tell you if any of these other medicines are CYP2D6 inhibitors. If they are, ask your doctor if you should change your treatment plan. If you're taking an antidepressant such as Prozac or Paxil that strongly inhibits the CYP2D6 enzyme, your doctor may want to switch 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 taking tamoxifen right now but hormonal therapy will be part of your treatment plan, go over all other medicines you're taking with your doctor. If any of your medicines are CYP2D6 inhibitors, your doctor should take that into consideration when recommending hormonal therapy treatment for you.

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