Some SSRIs inhibit tamoxifen, experts warn

THE use of a common selective serotonin reuptake inhibitor (SSRI) appears to inhibit the effect of tamoxifen and is associated with an increased risk of mortality from breast cancer.

The findings have led to calls for product warnings to be upgraded.

Canadian researchers found that among 2430 women treated with tamoxifen and a single SSRI, those concurrently using paroxetine had an increased risk of death. The effect was increased according to length of concurrent use and remained after adjustment for age, duration of tamoxifen treatment and other potential confounders.

The authors estimated that use of paroxetine for 41% of the tamoxifen treatment period would result in an additional cancer death within five years of treatment cessation for every 19.7 patients so treated.

“[This]…highlights a drug interaction that is extremely common, widely under-appreciated and uniformly avoidable,” the authors said. 

Professor Philip Mitchell, head of the school of psychiatry at the University of NSW, said based on these findings, warnings should be upgraded in the product information for both paroxetine and tamoxifen.

“The findings with paroxetine in this study are striking, and the inhibition of CYP2D6 as the explanatory mechanism seems well justified,” he said. Other SSRIs also impacted on tamoxifen, he added.

“Paroxetine, fluoxetine and fluvoxamine all have potent inhibitory effects on CYP2D6, whereas this is much less with sertraline and citalopram. 

Professor Mitchell recommended using antidepressants with low CYP2D6 inhibition including citalopram, venlafaxine, mirtazapine, sertraline or escitalopram.

A spokesperson said the TGA was reviewing the findings to determine whether the products’ PI required updating or strengthening.

BMJ 2010:340:c693