Antidepressant Blocks Benefits of Breast Cancer Drug

In women with breast cancer, tamoxifen significantly reduces the likelihood of recurrence and death due to breast cancer. But a study performed at the Institute for Clinical Evaluative Sciences (ICES) has found that a popular antidepressant, if taken simultaneously, can stop the benefits of tamoxifen and leave women at increased risk of death.

"Clinicians have suspected for years that some antidepressants, particularly paroxetine (Paxil and generics), might interfere with the beneficial effects of tamoxifen. But until now we've had no confirmation of the relevance of this drug interaction, and no sense of the risk it presents for patients", says Breast Medical Oncologist Dr. Catherine Kelly, who carried out this work while in the Breast Cancer Research Fellowship Program at Sunnybrook's Odette Cancer Centre.

Tamoxifen is a ‘prodrug,' meaning it must be converted into an active metabolite (endoxifen) by the liver in order to work. However, some drugs can interfere with this process. Antidepressants are of particular importance because they are commonly used by women with breast cancer, often for long periods of time. Although many antidepressants have little or no impact on tamoxifen's metabolism, paroxetine, a member of the so-called SSRI class, is a potent inhibitor of the metabolic step that converts tamoxifen to endoxifen.

"Our findings indicate that the choice of antidepressant can significantly influence survival in women receiving tamoxifen for breast cancer. This observation is consistent with what we know about tamoxifen's metabolism. These results highlight a drug interaction that is extremely common, widely underappreciated and potentially life-threatening, yet uniformly avoidable," says one of the study's authors and ICES Scientist Dr. David Juurlink.

The authors indicated that various treatment options exist for women receiving tamoxifen who require an antidepressant. However, they stressed the importance of not suddenly stopping paroxetine based upon these findings. "For women taking these two drugs together, I think there are better options for the treatment of depression. But it's important to realize that this is a marathon, not a sprint, and stopping paroxetine suddenly can cause its own set of problems," Juurlink suggests. If treatment changes are made, he adds, they should be done so gradually and only after consultation with a physician.