“Clinicians have suspected for years that some antidepressants, particularly paroxetine (Paxil and generics), might interfere with the beneficial effects of tamoxifen. But until now we’ve had no confirmation of the relevance of this drug interaction, and no sense of the risk it presents for patients,” says the study’s lead author and Breast Medical Oncologist, Dr. Catherine Kelly, who carried out this work while in the Breast Cancer Research Fellowship Program at Sunnybrook Odette Cancer Centre.
Tamoxifen is a ‘prodrug’, meaning it must be converted into an active metabolite (endoxifen) by the liver in order to work. However, some drugs can interfere with this process. Antidepressants are of particular importance because they are commonly used by women with breast cancer, often for long periods of time. Although many antidepressants have little or no impact on tamoxifen’s metabolism, paroxetine, a member of the so-called SSRI class, is a potent inhibitor of the metabolic step that converts tamoxifen to endoxifen.
The study examined 2,430 women aged 66 years or older with breast cancer living in Ontario who were treated with tamoxifen between 1993 and 2005. These women also received a SSRI anti-depressant medication while taking tamoxifen. Among the study’s findings were:
Use of an antidepressant with tamoxifen was common about 30 per cent of women were prescribed an antidepressant during tamoxifen therapy, and paroxetine was the most commonly used SSRI in the study.
Use of paroxetine, but NOT other SSRIs, in combination with tamoxifen, was associated with an increased long-term risk of breast cancer death, in a fashion that correlated with the extent of drug overlap.
Treatment with paroxetine for 41 per cent of the total time on tamoxifen (the median in this study) will result in one additional breast cancer death at 5 years for every 20 women so treated. The risk with more extensive overlap is greater.
“Our findings indicate that the choice of antidepressant can significantly influence survival in women receiving tamoxifen for breast cancer. This observation is consistent with what we know about tamoxifen’s metabolism. These results highlight a drug interaction that is extremely common, widely underappreciated and potentially life-threatening, yet uniformly avoidable,” says one of the study’s authors and ICES Scientist Dr. David Juurlink.
The authors indicated that various treatment options exist for women receiving tamoxifen who require an antidepressant. However, they stressed the importance of not suddenly stopping paroxetine based upon these findings. “For women taking these two drugs together, I think there are better options for the treatment of depression. But it’s important to realize that this is a marathon, not a sprint, and stopping paroxetine suddenly can cause its own set of problems.” Juurlink suggests if treatment changes are made, they should be done gradually and only after consultation with a physician.
Juurlink also cautioned against potential misinterpretation of the findings. Specifically, the results should not lead patients to stop taking tamoxifen, and do not imply that paroxetine itself causes or influences the course of breast cancer. “This is simply a situation in which paroxetine impairs the effectiveness of tamoxifen” he said, adding “There is an important silver lining to this story. This research gives breast cancer patients and their doctors fresh new insights into how we can optimize the benefits of tamoxifen – an inexpensive but tremendously important medication – simply by avoiding the use of other drugs that can interfere with it.
The study “Selective Serotonin Reuptake Inhibitors and Breast Cancer Mortality in Women Receiving Tamoxifen: A Population-Based Cohort Study” by Kelly et al. is in the February 8, 2010 of the British Medical Journal (BMJ).
More detailed study findings on the ICES website: www.ices.on.ca
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