The study reviewed here found that women taking the antidepressant Paxil (chemical name: paroxitene) at the same time as the hormonal therapy medicine tamoxifen were more likely to die from breast cancer than women taking tamoxifen who never took Paxil.
This result is similar to results from other research and suggests that Paxil interferes with tamoxifen's ability to treat breast cancer.
Tamoxifen is used to:
An enzyme called CYP2D6 helps tamoxifen work in the body. Some research has shown that women with an abnormal gene that blocks their bodies' ability to produce CYP2D6 don't get the same benefits from tamoxifen as women who produce CYP2D6.
Earlier research has shown that some medicines interfere with how CYP2D6 works, which reduces tamoxifen's effectiveness against breast cancer. These medicines include some antidepressants known as serotonin-specific reuptake inhibitors (SSRIs) -- including Paxil -- and serotonin-norepinephrine reuptake inhibitors (SNRIs). These antidepressant medicines are sometimes used to ease symptoms of depression or to manage hot flashes that can be a side effect of hormonal therapy in women being treated for breast cancer. Some other widely used medicines:
can block CYP2D6.
In this very large study, researchers looked at the medical records of more than 24,000 post-menopausal women diagnosed with hormone-receptor-positive breast cancer from 1993 to 2005. All the women were treated with tamoxifen and 7,500 of the women also took one or more of the following antidepressant medicines for some period of time while taking tamoxifen:
All of these are SSRI antidepressants except Effexor, which is an SNRI.
The researchers followed the women for about 2.4 years, comparing the outcomes of women who took an antidepressant to the outcomes of women who didn't. The researchers narrowed the study to compare the 2,430 women who took only one antidepressant while on tamoxifen to women who didn't take an antidepressant.
Most of the women who took only one antidepressant took Paxil (25.9%), followed by Zoloft (22.3%), Celexa (19.2%), Effexor (15%), Prozac (10.4%), and Luvox (7.2%).
Women who took Paxil for some period of time while taking tamoxifen were up to 91% more likely to die from breast cancer during the follow-up period compared to women who didn't take an antidepressant while taking tamoxifen. The increased risk of dying from breast cancer was different depending on how long a woman took Paxil and tamoxifen at the same time (called "therapeutic overlap"). Compared to women who never took Paxil, the likelihood of dying from breast cancer was:
Women who took an antidepressant other than Paxil had the same risk of dying from breast cancer as women who never took an antidepressant.
Still, other research has shown that Prozac, an SSRI, also strongly interferes with the CYP2D6 enzyme and decreases the benefits of tamoxifen.
The researchers think that Paxil's negative effects on tamoxifen were so strong in this study because Paxil's effect on the CYP2D6 enzyme is permanent (called "irreversible inhibition"). Other SSRI antidepressants do not inhibit the enzyme permanently.
If you're taking tamoxifen, tell your doctor about ALL other medicines you take, including vitamins, supplements, and over-the-counter medications. Your doctor can tell you if any of these other medicines are CYP2D6 inhibitors. If they are, ask your doctor if you should change your treatment plan. If you're taking an antidepressant such as Prozac or Paxil that strongly inhibits the CYP2D6 enzyme, your doctor may want to switch you to a different antidepressant. Your doctor also may recommend that you switch to a different hormonal therapy medicine, such as an aromatase inhibitor, that isn't affected by CYP2D6 inhibitors. Aromatase inhibitors can be a good alternative to tamoxifen for post-menopausal women. Aromatase inhibitors aren't recommended for pre-menopausal women.
If you're not taking tamoxifen right now but hormonal therapy will be part of your treatment plan, go over all other medicines you're taking with your doctor. If any of your medicines are CYP2D6 inhibitors, your doctor should take that into consideration when recommending hormonal therapy treatment for you.
Overlapping use of tamoxifen and the antidepressant paroxetine (Paxil) significantly increases the risk of breast cancer mortality, data from a large cohort of breast cancer patients showed.
The excess breast-cancer mortality risk ranged as high as 91%, depending on the duration of simultaneous use, researchers reported online in BMJ.
Women taking other antidepressants with tamoxifen, including other selective serotonin reuptake inhibitors (SSRIs), did not have an increased risk of breast cancer death.
"We estimate that use of paroxetine for 41% of tamoxifen treatment (the median overlap in our sample) would result in one additional breast cancer death within five years of cessation of tamoxifen for every 19.7 patients so treated; the risk with more extensive overlap would be greater," David Juurlink, MD, PhD, of Sunnybrook Health Sciences Center in Toronto, and colleagues concluded.
The findings add to an accumulation of evidence suggesting that inhibition of the cytochrome P450 2D6 isozyme (CYP2D6) may adversely affect outcomes in breast cancer patients taking tamoxifen. CYP2D6 is the principle catalyst for converting tamoxifen into endoxifen, a metabolite with 100-fold greater affinity for the estrogen receptor.
Multiple studies have shown that women who have a poor-metabolizer phenotype have lower levels of endoxifen, as do women treated with drugs that inhibit CYP2D6.
"Indeed, in patients who receive tamoxifen in addition to a CYP2D6 inhibitor, endoxifen concentrations vary inversely with the degree of CYP2D6 inhibition," the authors wrote.
Paroxetine is used to treat depression and vasomotor symptoms in breast cancer patients treated with tamoxifen. Paroxetine is not the only SSRI antidepressant used by breast cancer patients, but it is the only SSRI that irreversibly inhibits CYP2D6.
Whether the metabolic effects of CYP2D6 inhibition translated into adverse breast cancer outcomes had not been determined.
To examine the issue, Juurlink and colleagues compared prescribing data with clinical records of 24,430 breast cancer patients, ages 66 and older, who initiated tamoxifen therapy from 1993 to 2005. Of those, 7,500 also received an antidepressant.
Ultimately, the investigators narrowed the study population to 2,430 women who took a single SSRI during tamoxifen therapy. The most commonly prescribed SSRI was paroxetine (25.9%), followed by sertraline (22.3%), citalopram (19.2%), venlafaxine (15%), fluoxetine (10.4%), and fluvoxamine (7.2%).
During a mean follow-up of 2.38 years, 1,074 patients died, including 374 breast cancer deaths.
The analysis showed an increased risk of breast cancer death only among women taking paroxetine.
The breast cancer mortality risk increased with the duration of concomitant use of paroxetine and tamoxifen. As the duration of therapeutic overlap increased from 25%, to 50%, to 75% of time on tamoxifen, the excess risk of breast cancer death increased from 24%, to 54%, to 91%.
Investigators repeated the analysis, using death from any cause. Overlapping treatment with tamoxifen and paroxetine led to an increased mortality risk of 13%, 28%, and 46% as the duration of overlap increased from 25% to 75%.
The results suggest clear implications for use of SSRIs in breast cancer patients on tamoxifen, Frank Andersohn, MD, and Stefan Willich, MD, of Charite University in Berlin, wrote in an accompanying editorial.
"The straightforward answer is to avoid prescribing strong CYP2D6-inhibiting SSRIs (such as paroxetine or fluoxetine) for women with breast cancer who are prescribed tamoxifen, and to consider instead drugs with low potential to inhibit CYP2D6 (such as citalopram or venlafaxine)," they wrote.
For women who are already taking a potent inhibitor of CYP2D6, doctors should consider switching to a drug that does not inhibit the enzyme, they added. However, any switch should be accomplished gradually, as abrupt discontinuation of an antidepressant confers risk, as well, they noted.
Co-author Kathleen Pritchard disclosed relationships with sanofi-aventis, AstraZeneca, Roche, Pfizer, Ortho-Biotech, YM Biosciences, Novartis, Abraxis, Amgen, GlaxoSmithKline, Bristol Myers Squibb, and Roche
Primary source: BMJ Source reference: Kelly CM, et al "Selective serotonin reuptake inhibitors and breast cancer mortality in women taking amoxifen: a population based cohort study" BMJ 2010; 340: c693. DOI:10.1136/bmj.c693.
Breastcancer.org is a non-profit organization dedicated to providing information and community to those touched by this disease. Learn more about our commitment to providing complete, accurate, and private breast cancer information.
Breastcancer.org 7 East Lancaster Avenue, 3rd Floor Ardmore, PA 19003
©2011 Breastcancer.org - All rights reserved.
