Antidepressants That Interact With Tamoxifen

Some drugs can cancel out the anti-estrogen effects of hormone therapy

Cup of antidepressants

Jose A. Bernat Bacete/Moment/Getty Images

Tamoxifen is a hormone therapy drug taken by many premenopausal women after completing their initial treatments for estrogen receptor-positive breast cancer. To treat the side effects of tamoxifen and to help with depression, doctors often prescribe antidepressants. However, many antidepressants can potentially interfere with the benefits of tamoxifen.

Knowing about the potential interactions between tamoxifen and antidepressants is crucial if you are considering using any of these drugs. While there are many that are problematic in this regard, there are several options that are believed to be relatively safe.

Why Tamoxifen Is Used

Once you finish primary treatment of breast cancer—which may involve therapies such as surgery, chemotherapy, and radiation therapy—you may need to take tamoxifen. If your tumor is estrogen-receptor positive, hormone therapy can reduce the risk of cancer coming back (recurrence) by around 50 percent.

The choice of medication depends on where you are in relation to menopause. If you're premenopausal, tamoxifen is usually the drug of choice. (For those who are postmenopausal, or who are premenopausal but have received ovarian suppression therapy, an aromatase inhibitor is usually used instead.)

Estrogen-receptor positive breast cancer cells are fueled by estrogen your body makes naturally. The hormone binds to these cancer cells and aids in their growth. Tamoxifen works by binding itself to these receptors so that estrogen can't, essentially starving the cancer cells of their food.

The side effects of tamoxifen include menopausal-type symptoms such as hot flashes, low libido, and vaginal dryness. In recent years, however, researchers have learned that some antidepressant medications can reduce these symptoms, as well as treat the all-too-common depression that can accompany breast cancer.

However, combining antidepressants and tamoxifen can lead to problems of its own, which doctors discovered after antidepressant treatment became commonplace in women with breast cancer.

Breast Cancer and Depression

Not surprisingly, many women who have been treated for breast cancer develop depression. The combination of a life-threatening diagnosis, the side effects of treatment, and the changes to body image that go with treatment all set the stage for a large emotional impact.

Interaction Concerns

In your body, tamoxifen is metabolized to endoxifen. Endoxifen is 30 to 100 times stronger than tamoxifen and is responsible for most of the clinical effects. Tamoxifen is broken down to endoxifen by the cytochrome P450 enzyme CYP2D6 (plus others that are less important).

Any drugs that reduce the activity of CYP2D6—and there are many—can reduce this breakdown process and, hence, the amount of endoxifen that is produced. This, of course, means that your tamoxifen treatment may not work as intended—or, perhaps, at all.

Interactions between tamoxifen and other drugs are common, and this includes many medications in addition to antidepressants. Since many of these are commonly used drugs, including over-the-counter drugs such as Benadryl, it's important to talk to your doctor and pharmacist about any medication, over-the-counter preparation, or dietary supplement you are considering while you are on tamoxifen.

Since many people take tamoxifen for five to 10 years, this is even more important. Keep in mind that not all physicians are familiar with these interactions (and researchers are learning more about them all the time). What this means is that if you should go to urgent care with an infection, for example, talk to your oncologist or pharmacist before taking any medications that have been prescribed during that consultation.

Antidepressants and Their Risk

There's more to research about specific antidepressants and their effect on tamoxifen levels in the body, but thus far scientists have noted that different antidepressants can affect tamoxifen in different ways. Some, such as Prozac (fluoxetine) and Paxil (paroxetine), are strong 2D6 inhibitors, interfering with the conversion of tamoxifen to endoxifen and potentially leaving you at higher risk of cancer recurrence.

With other antidepressants, there is a moderate interaction, and with others, only a slight one. Meanwhile, some supplements believed to help alleviate depression can interact with tamoxifen as well.

The below table summarizes what is known about several antidepressants and supplements thus far.

Antidepressant Interaction With Tamoxifen
Antidepressant Degree of Interference  Recommendation

Paxil (paroxetine)

Prozac (fluoxetine)

Strong interference with antiestrogen benefit

Avoid use

Cymbalta (duloxetine)

Wellbutrin (bupropion)

Zoloft (sertraline)

Moderate interference with antiestrogen benefit Increased risk

Saint John's Wort (hypericum)

Modest inhibition of antiestrogen benefit Increased risk
Remeron (mirtazapine)

Mild interaction
Note: Remeron has not been well-studied for interaction with tamoxifen.

Slight risk
Celexa (citalopram)

Effexor (venlafaxine)

Lexapro (escitalopram)

Pristiq (desvenlafaxine)
Minimal interaction with tamoxifen  Best choices 
     

A Word From Verywell

If you are considering an antidepressant medication, have a careful discussion with your doctor. Also, periodically ask if anything has changed regarding the current understanding of potential interactions with your tamoxifen, as this is an area of active research.

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Article Sources

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  1. Cleveland Clinic, "Tamoxifen & Breast Cancer"

  2. Juurlink D. Revisiting the Drug Interaction Between Tamoxifen and SSRI Antidepressants. British Medical Journal. 2016. 354:i5309. doi: 10.1136/bmj.i5309

  3. Harvard Medical School, Harvard Health, "Antidepressants and tamoxifen"

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