A study published in the British Journal of Medicine suggests that the antidepressant paroxetine (Paxil ™; GlaxoSmithKline) may significantly increase the risk of breast cancer mortality in women who also take tamoxifen. The same magnitude of risk was not noted with five similar antidepressants.
It is estimated that up to 25% of women with breast cancer suffer from depression and many undergo treatment with antidepressants from the family of selective serotonin uptake inhibitors (SSRIs). However, some SSRIs are known to inhibit CYP2D, a catalyst required to convert tamoxifen to its more active form of endoxifen. This interaction has the potential to reduce or even eliminate the clinical benefit of tamoxifen.
A team of Canadian researchers compared prescribing data among 24,430 women with breast cancer who were at least 66 years of age and who had initiated tamoxifen therapy between 1993 and 2005. Of these, 7489 had also received at least one SSRI. The research team then narrowed the study to include 2430 women who took a single SSRI while on tamoxifen. The most commonly prescribed antidepressant was paroxetine (25.9%) followed by sertraline (Zoloft™; Pfizer) (22.3%); citalopram (Celexa™; Forest Pharmaceuticals) (19.2%); venlafaxine (Effexor™; Wyeth Pharmaceuticals) (15%); fluoxetine (Prozac™; Eli Lilly and Company) (10.4%); and fluvoxamine (Luvox™; Solvay Pharmaceuticals) (7.2%). The primary outcome measure was the relationship between mortality from breast cancer following completion of tamoxifen treatment and the amount of time that any single SSRI was taken simultaneously with tamoxifen.
During a mean follow-up of 2.3 years, 1074 women died, of which 374 died as the result of their breast cancer. Analysis revealed an increased mortality rate only among the women taking tamoxifen and paroxetine and that the risk increased with longer simultaneous use. The longer the two drugs were taken together, the breast cancer mortality increased. As the duration of the overlap went from 25% to 50% to 75% of the time on tamoxifen, the mortality rates increased from 24%, 54%, and 91%, respectively (P<0.05, all comparisons). The same type of results were seen when the analysis was repeated using death from any cause. As the rate of overlap rose from 25% to 75%, the mortality rates from any cause also increased to 13%, 27%, and 46%, respectively.
The limitations of the study include a lack of available information as to why the SSRI was prescribed, breast cancer stage, and individual genotypes.
The researchers estimate that one additional breast cancer death would occur among every 20 women within 5 years of completing tamoxifen if they had also taken paroxetine for 41% of the time. Mortality would likely increase as the length of simultaneous use increased. The authors suggest that clinicians switch patients who currently take paroxetine to one of the antidepressants that do not inhibit CYP2D6. However, any switch should be done gradually, as abrupt discontinuation of paroxetine can lead to the emergence of psychological and somatic symptoms.