Breast Cancer, Depression, and Tamoxifen: A Dangerous Trio

Patient Expert

Do you have breast cancer, or are you at high risk for it? Are you taking an antidepressant? Are you on tamoxifen?

If you answered "yes" to these three questions, read on: the following information could literally save your life.

For more than 30 years, tamoxifen (e.g., Nolvadex) was the gold standard for long-term treatment of women with estrogen-receptive (ER/PR+) breast cancer - the majority of breast cancer survivors.

Abut 10 years ago, another class of drugs, aromatase inhibitors (Arimidex, Femara, and Aromasin) began to replace tamoxifen as the gold standard for post-menopausal survivors. Still, if you're pre-menopausal (and in some cases even if you're post-), you're probably taking tamoxifen.

Now, it appears increasingly likely that women who take tamoxifen in conjunction with certain other drugs (mainly antidepressants) may not have been getting the anti-cancer benefit they thought they were.

Preliminary results of a large study linking antidepressants with tamoxifen effectiveness, completed in 2005, began to surface in the popular media about 3 years ago. And at last year's meeting of the American Society of Clinical Oncology, the complete study was released: certain antidepressants can inhibit tamoxifen's effectiveness. Significantly.

The study showed that women who took the antidepressant Paxil during the entire course of their tamoxifen treatment were 91% more likely (nearly twice as likely) to die of breast cancer as women who didn't take an antidepressant. Women who took Paxil only part of the time showed lesser (though still increased) risk.

Another study showed the same types of results for Prozac, another antidepressant.

What's the connection here? Your body's CYP2D6 enzyme, which is responsible for converting tamoxifen into a cancer fighter. If this enzyme is blocked (inhibited), tamoxifen won't work.

Doctors have long known that certain drugs are CYP2D6 inhibitors. But it's only recently that the CYP2D6-tamoxifen connection has been identified.

And while we know which drugs are CYP2D6 inhibitors, complete studies haven't yet been done to prove which ones reduce tamoxifen's effectiveness, and by how much. Only the aforementioned studies targeting Paxil and Prozac have been completed.

Still, why take a chance that a drug you take, a known CYP2D6 inhibitor, may be increasing your risk of cancer recurrence? Antidepressants Wellbutrin, Cymbalta, and Zoloft have been identified as moderate to strong CYP2D6 inhibitors. As have Tagamet   and Zantac, both very common heartburn relief remedies. And Celebrex, taken by millions for arthritis. And Benadryl, a widely used antihistamine.

In addition, the Mayo Clinic Web site notes the fact that up to 10% of Caucasians (and 2% of African-Americans, and 1% of Asians) are naturally deficient in CYP2D6. If you happen to be in that group, then tamoxifen might not be effective for you.

So what's the bottom line here? If you're taking tamoxifen, make a list of everything else you're taking: drugs, vitamins, and supplements. Show the list to your doctor, and ask him/her to identify which ones are potential CYP2D6 inhibitors.

If it turns out you're taking a CYP2D6 inhibitor, consider switching to a different medication. Among antidepressants, Celexa, Effexor, and Lexapro are all weak CYP2D6 inhibitors, and would probably be your best choice.

Finally, if you're about to start taking tamoxifen, or have only been on it for a short while, ask your doctor for the CYP2D6 test, to see if you're naturally deficient in this enzyme. If you are, you might want to discuss a switch from tamoxifen to an aromatase inhibitor.