Antidepressants That Interact With Tamoxifen

Some drugs can decrease the anti-estrogen effects of hormone therapy

Tamoxifen is a medication that is used to treat estrogen-receptor-positive breast cancer, typically in premenopausal people. It is not uncommon for those taking tamoxifen to also be taking an antidepressant medication. An antidepressant may be needed to treat depression associated with having cancer or possibly as a way to help manage hot flashes, a common side effect of tamoxifen. However, some antidepressants can interfere with the benefits of tamoxifen.

Cup of antidepressants
Jose A. Bernat Bacete / Moment / Getty Images

Knowing the potential interactions between tamoxifen and antidepressants is important if you are taking these types of medications. Not all antidepressants have this interaction and can be safe to use along with tamoxifen.

This article will review the use of tamoxifen, the potential interactions with antidepressants, and which ones may be safer to take.

Why Tamoxifen Is Used

Once the initial treatment of breast cancer is completed—which may involve therapies such as surgery, chemotherapy, and radiation therapy—taking hormonal therapy may be recommended. If your tumor is estrogen-receptor positive, hormone therapy can reduce the risk of cancer coming back.

For those people who are premenopausal, tamoxifen is usually the medication used. 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 that naturally occurs in the body. Estrogen attaches 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 sex drive, and vaginal dryness. It has been found that some antidepressant medications can reduce these symptoms, as well as treat depression that may accompany breast cancer.

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

Breast Cancer and Depression

Not surprisingly, many people 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 significant emotional impact.

Interaction Concerns

In your body, tamoxifen is broken down as it is digested and turns into endoxifen. Endoxifen is stronger than tamoxifen and is responsible for most of the clinical effects. The pathway in which tamoxifen is broken down is through something called the cytochrome P450 enzyme CYP2D6.

Any drugs that reduce the activity of the CYP2D6 enzyme—and there are many—can reduce this breakdown process and prevent endoxifen from being 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, it's important to talk to your healthcare provider 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 healthcare providers are familiar with these interactions. 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 visit.

Antidepressants and Their Risk

It has been found that some classes of antidepressants are more likely to interfere with tamoxifen than others. Medications that are strong CYP2D inhibitors, such as Prozac (fluoxetine) and Paxil (paroxetine), interfere with the conversion of tamoxifen to endoxifen, decreasing the ability of the drug to prevent 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 we know 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
Celexa (citalopram) Effexor (venlafaxine) Lexapro (escitalopram) Minimal interaction with tamoxifen  Best choices 


Tamoxifen is an important medication used to treat estrogen-receptor positive breast cancer. Caution should be used when it is taken along with antidepressant medications, as some of them interfere with the way tamoxifen works at decreasing the risk of breast cancer recurrence.

Antidepressants such as Paxil or Prozac should be avoided, while others, such as Celexa or Lexapro, may be a safer option.

A Word From Verywell

If you are considering an antidepressant medication, have a careful discussion with your healthcare provider. 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.

Frequently Asked Questions

  • Can you take antidepressants with breast cancer?

    Yes, antidepressants can be taken when someone has breast cancer. It should be a careful decision made with the healthcare team to find the safest medication to take.

  • Is there a link between antidepressants and breast cancer?

    Studies have not shown any increased risk of developing breast cancer because of the use of antidepressants. However, taking certain antidepressants while taking tamoxifen may keep the tamoxifen from working properly, potentially increasing the risk of breast cancer coming back.

  • What drugs should not be taken with tamoxifen?

    Medications that should not be taken along with tamoxifen include the antidepressants Paxil, Wellbutrin, and Prozac. Other medications that may need to be used cautiously or avoided also include Benadryl, Amiodarone, and Zoloft.

  • Is depression a side effect of tamoxifen?

    Yes, depression can be a side effect of tamoxifen.

6 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Juurlink D. Revisiting the drug interaction between tamoxifen and SSRI antidepressantsBMJ. 2016;354:i5309.

  2. Cleveland Clinic. Tamoxifen and breast cancer.

  3. Juurlink D. Revisiting the Drug Interaction Between Tamoxifen and SSRI Antidepressants. BMJ. 2016;354:i5309. doi:10.1136/bmj.i5309

  4. Harvard Health Publishing. Antidepressants and tamoxifen.

  5. Brown SB, Hankinson SE, Arcaro KF, Qian J, Reeves KW. Depression, antidepressant use, and postmenopausal breast cancer riskCancer Epidemiol Biomarkers Prev. 2016;25(1):158-164.

  6. Tamoxifen.

Additional Reading

By Julie Scott, MSN, ANP-BC, AOCNP
Julie is an Adult Nurse Practitioner with oncology certification and a healthcare freelance writer with an interest in educating patients and the healthcare community.

Originally written by Pam Stephan
Pam Stephan is a breast cancer survivor.
Learn about our editorial process