(February 8, 2010 - Insidermedicine)

The antidepressant paroxetine, which is a potent irreversible inhibitor of the CYP2D6 metabolic pathway, interferes with the metabolism and thus the efficacy of tamoxifen when used for breast cancer, according to a population cohort study published in the British Medical Journal.
 
Here are some recommendations for the management of depression in patients with cancer, from Cancer Care Ontario:
 
    •    Antidepressant medications should be considered to treat moderate to severe major depression in cancer patients.
 
    •    Cancer patients diagnosed with major depression may benefit from a combined modality approach that includes both psychosocial and pharmacological interventions.
 
    •    Psychosocial treatment approaches that may be of value include those that provide information and support and which address emotional, cognitive, and/or behavioral factors.
 
Researchers out of Sunnybrook Odette Cancer Centre in Toronto and the Institute for Clinical Evaluative Sciences (ICES) analyzed the outcomes of 2,430 women aged 66 and older who were living in Ontario. All participants were treated with tamoxifen for breast cancer between 1993 and 2005 and also had overlapping therapy with a single SSRI.
 
The overall mortality rate from breast cancer was 15.4%. After adjusting for age, duration of tamoxifen therapy, and other potential confounders, paroxetine use overlapping with tamoxifen use was associated with an increased risk of death from breast cancer. The more time spent on paroxetine while on tamoxifen, the higher the mortality rate. The authors estimate that use of paroxetine for 41% of tamoxifen therapy would result in 1 additional breast cancer death within five years for every 20 women treated. No such risk increase was seen with other antidepressants.

 We spoke with Dr. David Juurlink, one of the investigators of this study, who offered some further insight.
 
Today’s research suggests that women being treated with tamoxifen for breast cancer should not receive concomitant therapy with paroxetine, and caution should be applied when using other CYP2D6 inhibitors in this patient population.