What is the best antidepressant to take with tamoxifen? (3 options)

In this article, we will discuss the most suitable antidepressants to take with tamoxifen – an anticancer drug. We will also talk about some potential risks of these combinations and how one can ensure the safe and effective use of these meds together. 

What is the best antidepressant to take with tamoxifen?

The best antidepressants to take with tamoxifen are:

  • Serotonin-norepinephrine reuptake inhibitors (SNRIs) – venlafaxine and desvenlafaxine
  • Selective serotonin reuptake inhibitors (SSRIs) – sertraline, citalopram, escitalopram, etc.
  • Atypical antidepressants – mirtazapine 

Tamoxifen is a medication used to manage and treat breast cancer (1). The major concern when combining tamoxifen with an antidepressant is the potential reduction in the effectiveness of tamoxifen, which could be life-threatening considering the serious condition it treats. 

Tamoxifen is primarily metabolised by the cytochrome P450 enzyme system. This medication converts via CYP2D6 to endoxifen, an active metabolite of the drug possessing strong anticancer activity (1). 

Some antidepressants are potent inhibitors of CYP2D6, making the conversion of tamoxifen difficult and reducing the anticancer activities of the drug. This is the main reason why antidepressants are carefully prescribed with tamoxifen.

Let’s discuss the above-mentioned drugs in detail:

Serotonin-norepinephrine reuptake inhibitors (SNRIs)

SNRIs such as venlafaxine and desvenlafaxine are good antidepressants to pair with tamoxifen. Venlafaxine, in particular, can be considered the drug of choice, as research suggests that it has little to no effect on CYP2D6 and the overall metabolism of tamoxifen into its active metabolites (2). 

This indicates that venlafaxine does not affect the anticancer activity of the drug and can be used with it to manage depression in individuals with breast cancer. Desvenlafaxine, another SNRI, can also be taken, as this antidepressant does not affect the CYP2D6 system

Duloxetine is considered a weak inhibitor of CYP2D6, so its use should be cautiously monitored.

Selective serotonin reuptake inhibitors (SSRIs)

Some selective serotonin reuptake inhibitors (SSRIs), such as sertraline, are considered weak inhibitors of CYP2D6 and may be used in patients receiving tamoxifen in certain cases (2,3). However, some SSRIs are potent inhibitors of CYP2D6, such as paroxetine and fluoxetine, which should never be taken with tamoxifen. 

Research studies have indicated that paroxetine is a strong irreversible inhibitor of CYP2D6, significantly affecting the metabolism and anticancer effects of tamoxifen, leading to an increased risk of death from breast cancer (2,3). 

This indicates that some SSRIs should never be paired with anticancer drugs such as tamoxifen. Weak inhibitors might be considered in some cases, but doctors still need to weigh the pros and cons before opting for these medications.

Atypical antidepressants

Some atypical antidepressants such as mirtazapine might be considered to pair with tamoxifen. However, there is a lack of research when it comes to the use of these antidepressants with tamoxifen. Bupropion, however, should be avoided with tamoxifen as it can inhibit the CYP2D6 system (2). 

It may not cause an effect as significant as paroxetine or fluoxetine, but the inhibitory effects can be clinically significant in some cases. 

The use of mirtazapine, vortioxetine, vilazodone, etc, has not been studied much, and more research is required to determine their safety and efficacy when paired with tamoxifen. However, these antidepressants are not considered to inhibit CYP2D6 (2).

Summarising the effects of common antidepressants on the CYP2D6 enzyme system:

Antidepressants CYP2D6 Inhibition
Venlafaxine Little to no effect
Desvenlafaxine Little to no effect
Mirtazapine Little to no effect

What are the potential risks of taking tamoxifen with antidepressants?

The choice of the right antidepressant while being treated for breast cancer should be made by a qualified healthcare professional. Enzyme inhibition might not be the only point you need to be concerned about. 

Patients with cancer have a lot of different symptoms that could worsen when drugs like antidepressants are taken, which can cause side effects. Anticancer drugs, including tamoxifen, are quite heavy on the body and are associated with a number of side effects, some of which could be severe. 

So, your doctor might not burden you more by adding an antidepressant to your regimen if it is not absolutely needed, and you should also avoid taking any medication without consulting your doctor first. 

How to ensure the safe and effective use of tamoxifen with antidepressants?

The following ways are important to ensure the safe and effective use of tamoxifen with antidepressants:

  • Before adding antidepressants to your cancer treatment, talk to your doctor. They’ll check your health and see if you need antidepressants.
  • If you need antidepressants, the doctor may change how much you take. This helps avoid problems and makes sure you get the best treatment.
  • Your doctor will keep an eye out for any issues when you take both medicines. They’ll check if everything is going okay or if there are any unusual effects.
  • Everyone is different. Your age, how healthy you are, and the type of antidepressant you take are all important. Your doctor will look at all these things to decide what’s best for you.
  • You’ll need to visit your doctor often. This is to check how you’re doing, if there are any side effects, and if anything needs to be changed. Talking openly with your doctor helps a lot.

As a pharmacist, I always recommend following your prescriber’s directions properly. When it comes to diseases like cancer, which can affect your entire body and are life-threatening, proper use of medications, a balanced diet, and attention to lifestyle factors are crucial.

It’s not uncommon for cancer patients to experience depression due to the challenging nature of the disease. While your doctor might consider a low dose of a suitable antidepressant if your depression becomes severe, it’s generally best to approach this cautiously. 

Medications used for cancer treatment are potent and often come with numerous side effects. It’s important to watch out for potential drug interactions to prevent any worsening of your condition. Remember, relying on your doctor’s expertise and actively participating in your care is key to improving the quality of your life.


  1. Farrar MC, Jacobs TF. Tamoxifen. 2023 Apr 10. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan–. PMID: 30422500. https://www.ncbi.nlm.nih.gov/books/NBK532905 
  1. Desmarais JE, Looper KJ. Interactions between tamoxifen and antidepressants via cytochrome P450 2D6. J Clin Psychiatry. 2009 Dec;70(12):1688-97. doi: 10.4088/JCP.08r04856blu. PMID: 20141708. https://pubmed.ncbi.nlm.nih.gov/20141708/ 
  1. Kelly CM, Juurlink DN, Gomes T, Duong-Hua M, Pritchard KI, Austin PC, Paszat LF. Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study. BMJ. 2010 Feb 8;340:c693. doi: 10.1136/bmj.c693. PMID: 20142325; PMCID: PMC2817754. https://pubmed.ncbi.nlm.nih.gov/20142325/ 

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