Tamoxifen and anti-depressants – pro
More than 500,000 women in the U.S. are taking tamoxifen and about 30% of those women are also prescribed antidepressants. A recent study in 2009 ASCO raised the possiblity that tamoxifen interacts negatively with newer anti-depressants. The retrospective study involved about 1,300 women who were taking antidepressants like Paxil, Prozac and Zoloft along with tamoxifen for at least one year had a breast-cancer recurrence rate of 16% — compared with a recurrence rate of 7.5% for women not taking the drugs. However,women on drugs like Celexa, Lexapro and Luvox didn’t have a statistically higher rate of cancer recurrence. However, a similar study, also presented at the meeting, showed no effect of SSRIs on the risk for breast cancer recurrence in women taking tamoxifen. This study was conducted in the Netherlands, and involved 1962 women who were taking tamoxifen after surgery for early-stage breast cancer. About 11% had also taken an SSRI (most commonly fluoxetine and paroxetine) at some point.
The association has been found again in a 2010 study of 2,430 elderly women (66 years or older) with breast cancer who were treated with tamoxifen and a single selective serotonin reuptake inhibitor, most commonly paroxetine, between 1993 and 2005.
After adjusting for several factors, overlapping treatment with tamoxifen and paroxetine was associated with a higher risk of death from breast cancer, and a greater extent of overlap was associated with a greater risk of death. For the median overlap of 41 percent, the authors estimated that there would be one additional breast cancer death for every 19.7 patients within five years of stopping tamoxifen treatment. The editorial that accompanied this article in the British Medical Journal recommended avoidance of strong CYP2D6-inhibiting SSRIs, such as paroxetine and fluoxetine, and to instead consider instead drugs with low potential to inhibit CYP2D6, such as citalopram or venlafaxine.
Preskorn, SH. Clinically relevant pharmacology of selective serotonin reuptake inhibitors. An overview with emphasis on pharmacokinetics and effects on oxidative drug metabolism. Clin Pharmacokinet. 1997;32 Suppl 1:1-21.
Goetz MP, Knox SK, Suman VJ, Rae JM, Safgren SL, Ames MM, Visscher DW, Reynolds C, Couch FJ, Lingle WL, Weinshilboum RM, Fritcher EG, Nibbe AM, Desta Z, Nguyen A, Flockhart DA, Perez EA, Ingle JN.. The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen. Breast Cancer Res Treat. 2007 Jan;101(1):113-21. Epub 2006 Nov 18.
Rapkin, AJ. Vasomotor symptoms in menopause: physiologic condition and central nervous system approaches to treatment. Am J Obstet Gynecol. 2007 Feb;196(2):97-106.
Jin Y, Desta Z, Stearns V, Ward B, Ho H, Lee KH, Skaar T, Storniolo AM, Li L, Araba A, Blanchard R, Nguyen A, Ullmer L, Hayden J, Lemler S, Weinshilboum RM, Rae JM, Hayes DF, Flockhart DA. CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J Natl Cancer Inst. 2005 Jan 5;97(1):30-9
Catherine M Kelly et al, Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study BMJ 2010;340:c693, 2010
Charles L. Loprinzi, Jeff Sloan, Vered Stearns, Rebecca Slack, Malini Iyengar, Brent Diekmann, Gretchen Kimmick, James Lovato, Paul Gordon, Kishan Pandya, Thomas Guttuso, Jr, Debra Barton, and Paul Novotny J Clin Oncol. 2009 June 10; 27(17): 2831–2837.