How to Use Tamoxifen and Antidepressants Safely

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Tamoxifen and antidepressants are often prescribed for people with breast cancer. Tamoxifen is used for the treatment of estrogen-receptor-positive breast cancer, while antidepressants help treat depression and reduce hot flashes (a common side effect of tamoxifen).

Even so, certain antidepressants can reduce the effectiveness of tamoxifen by interfering with how the body breaks it down. Antidepressants called selective serotonin reuptake inhibitors (SSRIs) pose the greatest risk, but other classes of antidepressants may also be of concern.

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

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

Benefits of Tamoxifen

Tamoxifen is a cancer drug approved by the U.S. Food and Drug Administration (FDA) for the treatment of estrogen-receptor-positive breast cancer. This is a form of breast cancer fueled by the hormone estrogen.

Not all breast cancers have estrogen receptors, but for those that do, tamoxifen can bind to the receptors and block the effects of estrogen. Doing so can slow or even stop the spread of cancer.

Your cancer specialist will perform tests before treatment to determine if the cancer you have is estrogen-receptor positive (ER+) or estrogen-receptor negative (ER-).

If your cancer is ER+, tamoxifen may be prescribed for one of four reasons:

Antidepressants and Breast Cancer

Antidepressants are widely used to treat depression in people undergoing cancer treatment. A 2022 study in Frontiers in Public Health reported that one in five cancer survivors use antidepressants, most commonly selective serotonin reuptake inhibitors (SSRIs) like Prozac and Paxil.

The use of antidepressants is fueled by high rates of depression. Among people with breast cancer, the rate may be as high as 33%.

Antidepressants can be valuable in more ways than one. Studies have shown that clinical depression independently increases the risk of breast cancer recurrence by 24% and breast cancer mortality by 29%. As such, treating depression may improve outcomes.

In addition to treating depression, antidepressants may help ease some of the side effects of tamoxifen. Chief among these are hot flashes and night sweats (known as vasomotor symptoms) which affect no less than 64% of females on tamoxifen.

The SSRI paroxetine not only reduces hot flashes but was licensed for such use by the FDA under the brand name Brisdelle.

Risks of Interaction With Tamoxifen and Antidepressants

As useful as antidepressants can be in the treatment of cancer, they pose significant risks when used with tamoxifen. This is because of the way that certain antidepressants affect the metabolization (breaking down) of the drug, which reduces the effectiveness of tamoxifen.

All drugs are dosed based on the expected rate of metabolization. With tamoxifen, an enzyme called CYP2D6 is tasked with breaking it down into its active and inactive components. The active component, called endoxifen, is the one that binds to estrogen receptors on cancer cells.

SSRIs are problematic because several are strong CYP2D6 inhibitors. By blocking the effects of CYP2D6, less endoxifen is released and the overall effectiveness of tamoxifen is reduced. This can reduce your chances of remission or increase your odds of recurrence.

There are five SSRIs licensed for the treatment of depression, two of which are strong CYP2D6 inhibitors that need to be avoided if taking tamoxifen:

Another SSRI called Zoloft (sertraline) is a moderate CYP2D6 inhibitor that can potentially cause problems if taking tamoxifen. Unless there is a reason why Zoloft cannot be changed, it may be in your best interest to switch out of the utmost caution.

Antidepressants That Are Safe to Use With Tamoxifen

Not all antidepressants are avoided if you are taking tamoxifen, including certain SSRIs. Two SSRIs considered relatively safe with tamoxifen include:

Another class of antidepressants called selective serotonin-norepinephrine reuptake inhibitors (SNRIs) are weak to moderate CYP2D6 inhibitors. The two that are least likely to interact with tamoxifen include:

Another class, called tricyclic antidepressants, may also be suitable. Of the tricyclic antidepressants licensed for use by the FDA, four are weak CYP2D6 inhibitors that are likely safe with tamoxifen:

It is important to note that some antidepressants are more effective than others and some have side effects that make them less attractive.

To make an informed choice, speak with your healthcare provider to fully understand the benefits and potential risks of any antidepressant you take. If needed, ask for a referral to a psychiatrist who is trained in the appropriate use of antidepressants.

Summary

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 that tamoxifen works. Antidepressants such as Paxil or Prozac should be avoided for this reason, while others, such as Celexa or Lexapro, may be safer options.

8 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.
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  4. Rosemont Pharmaceutical. Soltamox (tamoxifen citrate) oral solution, September 2018.

  5. Busby J, Mills K, Zhang SD, et al. Selective serotonin reuptake inhibitor use and breast cancer survival: a population-based cohort studyBreast Cancer Res. 2018;20:4. doi:10.1186/s13058-017-0928-0

  6. Wang X, Wang N, Zhong L, et al. Prognostic value of depression and anxiety on breast cancer recurrence and mortality: a systematic review and meta-analysis of 282,203 patientsMol Psychiatry. 2020;25:3186–3197. doi:10.1038/s41380-020-00865-6

  7. Sabela Pharmaceuticals. Brisdelle (paroxetine) capsules, for oral use. January 2017.

  8. BC Cancer (Canada). Drug name: tamoxifen. May 2024.

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By Julie Scott, MSN, ANP-BC, AOCNP
Scott is an Adult Nurse Practitioner and health writer with experience in oncology and hematology.

Originally written by Pam Stephan