Do SSRIs reduce the efficacy of tamoxifen?

January 01, 0001

Do SSRIs reduce the efficacy of tamoxifen?

These Canadian authors sought to characterize whether selective serotonin reuptake inhibitors(SSRIs) reduce tamoxifen’s effectiveness, possibly via inhibiting bioactivation by cytochrome P450 2D6 (CYP2D6). They implemented a population based cohort study involving women in Ontario aged 66 years or older who were treated with tamoxifen for breast cancer with overlapping SSRI treatment. The primary outcome was the risk of death from breast cancer as a function of the proportion of time on tamoxifen during which each SSRI had been co-prescribed.

The researchers report: "Of 2430 women treated with tamoxifen and a single SSRI, 374 (15.4%) died of breast cancer during follow-up (mean follow- up 2.38 years). After adjustment for age, duration of tamoxifen treatment, and other potential confounders, absolute increases of 25%, 50%, and 75% in the proportion of time on tamoxifen with overlapping use of paroxetine (an irreversible inhibitor of CYP2D6) were associated with 24%, 54%, and 91% increases in the risk of death from breast cancer, respectively. By contrast, no such risk was seen with other antidepressants. 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."

The researchers concluded: "Paroxetine use during tamoxifen treatment is associated with an increased risk of death from breast cancer, supporting the hypothesis that paroxetine can reduce or abolish the benefit of tamoxifen in women with breast cancer."

This study strongly recommends against the use of paroxetine in women undergoing treatment with tamoxifen.

For the full abstract, click here.

BMJ 340:c693, 8 February 2010
© 2010 Kelly et al.
Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen- a population based cohort study. Catherine M Kelly, David N Juurlink, Tara Gomes, et al.. Correspondence to D N Juurlink: [email protected]

Category: X. Female Genital System, Breast. Keywords: SSRI, paroxetine, tamoxifen, breast cancer, depression, cohort study, journal watch.
Synopsis edited by Dr Paul Schaefer, Toledo, Ohio. Posted on Global Family Doctor 26 March 2010

Pearls are an independent product of the Cochrane primary care group and are meant for educational use and not to guide clinical care.