Tamoxifen and SSRIs:  DO NOT MIX.

Jacob Schor ND FABNO

June 1, 2009


The 45th annual meeting of the American Society of Clinical Oncologists is underway.  Already articles are appearing in our local newspaper about the new findings being reported.

One article that caught my eye last week because it should change the way many patients are treated was about tamoxifen and antidepressants.   According to a MedScape summary, “Until there are more data, patients who are taking tamoxifen to reduce their risk for breast cancer recurrence should avoid concomitant use of selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac), paroxetine (Paxil), and sertraline (Zoloft).” (1)

There is little about having breast cancer that is fun.  Many women who are being treated for breast cancer find themselves depressed and doctors have been happy to prescribe antidepressants to them.  Doctors though are very hesitant to prescribe any sort of hormone replacement for these women to treat hotflashes.  Often as not they are put on antidepressants to treat the hotflashes as well as depression.

The problem is that some of these antidepressant drugs inhibit an enzyme called cytochrome P450-2D6.  This enzyme is responsible for converting the drug tamoxifen into its active metabolite, endoxifen.  Premenopausal women typically take tamoxifen for five years as part of their treatment.   If tamoxifen isn’t turned into endoxifen it appears not to prevent cancer recurrence like it is supposed to. 

One study looked at data collected an health benefits company called MEDCO.  Analyzing data collected on their 11 million members, researchers from Indiana University identified 945 women over 50 years old who had taken tamoxifen for 2 years or more.  Of these women, 353 were also taking an SSRI antidepressant.

The women taking the SSRI along with tamoxifen had about double the risk for breast cancer recurrence of those taking tamoxifen alone.    Risk for breast cancer recurrence was 7% in women not taking SSRIs and 16% in women taking SSRIs.  Exactly how much risk increased varied with how strong an inhibitory effect the drug had on the enzyme cytochrome P450 2D6.  Drugs with a weak effect on the enzyme did not have a statistically significant effect on cancer recurrence risk, only 8.8%.


Drugs that are strong inhibitors and that increase risk of cancer recurrence include: fluoxetine (Prosac), paroxetine (Paxil), and sertraline (Zoloft).

Weak inhibitors include citalopram (Celexa), escitalopram (Lexapro), and fluvoxamine (Luvox).

This is a big deal because it isn’t rare to combine these drugs.  About 30% of women taking tamoxifen are taking one of these drugs.

If you are taking tamoxifen, you should not take Prosac, Paxil, or Zoloft.  This is pretty clear except for one detail.  Another study also presented at ASCO, didn’t find a problem. 

This second study was conducted in the Netherlands, and involved 1962 women who were taking tamoxifen after surgery for breast cancer. Only 11% had taken an SSRI antidepressant, mostly Prosac or Paxil.  [1]   The experts are ignoring these negative results as there were too few women taking both drugs at the same time to create significant data.

If this discussion seems vaguely familiar, it should be.  This worry isn’t new.

These studies aren’t the first to bring up a worry that breast cancer risk is affected by using antidepressants.   A study published back in 2000 told us that using antidepressants for more than two years doubled risk of breast cancer and one drug in particular, Paxil, used for 2 years, increased risk by a factor of 7.[2] 


A paper published in 2005 in the Journal of the National Cancer institute told us that taking the wrong SSRI with tamoxifen lowered production of the active metabolite endoxifen by 58%. [3]   This came as no surprise.  The year before at the 2004 ASCO meeting researchers had predicted this might well be the case. [4]   Even so, the study authors advised, “Prescribing practices should not be changed at present.”

For our long time readers, this all should be old hat.  We’ve sent out several past newsletters warning not to mix these drugs.  We do try to take that Hippocratic injunction, ‘primo non nocere,’ seriously. 

An earlier newsletter covers this chemistry in more detail.




 (1) Chustecka Z. Avoid SSRIs in Breast Cancer Patients on Tamoxifen. Medscape Medical News ASCO 2009:

(2)Cotterchio M et al. Antidepressant medication use and breast cancer risk.  Am J Epidemiol. 2000 May 15;151(10):951-7.

(3) Jin Y, et al. CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J Natl Cancer Inst. 2005 Jan 5;97(1):30-9. 

(4) V. Stearns et al.  Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 22, No 14S (July 15 Supplement), 2004: 508 2004 American Society of Clinical Oncology