Antidepressant may weaken effect of tamoxifen in patients with breast cancer

The selective serotonin reuptake inhibitor paroxetine may inhibit the effectiveness of tamoxifen when the drugs are coprescribed in patients with breast cancer, according to a new study.

Tamoxifen, a drug that requires bioactivation by cytochrome P450 2D6 (CYP2D6), is commonly prescribed to treat estrogen-receptor positive breast cancer. Patients with breast cancer are also frequently prescribed antidepressants, either to treat depression or to mitigate the hot flushes associated with tamoxifen treatment. Selective serotonin reuptake inhibitors (SSRIs), however, are known to inhibit CYP2D6. Canadian authors performed a population-based cohort study to determine whether SSRIs lessen tamoxifen's effectiveness in women with breast cancer who are prescribed both drugs.

The authors looked at 2,430 women from Ontario, Canada, who were at least 66 years old, had been treated with tamoxifen for breast cancer between 1993 and 2005, and had received concomitant treatment with an SSRI. Most women were prescribed paroxetine (25.9%), followed by sertraline (22.3%), citalopram (19.2%), venlafaxine (15.0%) fluoxetine (10.4%) and fluvoxamine (7.2%). Seven hundred thirty-five patients received one or more non-SSRI antidepressants. By the end of follow-up (mean, 2.38 years; SD 2.59), 1,074 women (44.2%) had died, 374 (15.4%) of breast cancer. Patients whose use of tamoxifen overlapped with use of the SSRI paroxetine were more likely to die of breast cancer than those who had no such overlap; similar risk was not seen with other SSRIs. The study results were published online Feb. 8 by BMJ.

The authors noted that they were unable to determine the reason for antidepressant treatment and had no information on patients' breast cancer stage. However, their findings have strong implications for clinical practice, they wrote, because of the frequent use of combination therapy in women with breast cancer. They concluded that antidepressant choice can have a significant effect on survival in women with breast cancer who are taking tamoxifen, calling the drug interaction "extremely common, widely underappreciated and uniformly avoidable." An accompanying editorial noted that "a switch to an antidepressant with low or no CYP2D6 inhibitory activity should be considered in patients who are already treated with tamoxifen and paroxetine or fluoxetine." However, the editorialists cautioned that fluoxetine and paroxetine treatment should not be abruptly stopped, and called for more study on the clinical effects of the interactions between these drugs and tamoxifen as well as replication of the current study's findings in other populations.