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Mortality higher if using paroxetine and tamoxifen

Taking paroxetine with tamoxifen raises breast cancer mortality

OnMedica staff

Wednesday, 10 February 2010

Research published in the BMJ supports the theory that paroxetine reduces or abolishes the beneficial effect of tamoxifen in treating breast cancer, and women taking tamoxifen should take alternative antidepressants if needed.

This study included 2430 women in Ontario, Canada, who had begun tamoxifen treatment for the first time when they were at least 66 years old. Researchers examined records from 1993 to 2005 for co-prescription of a single antidepressant during tamoxifen treatment. They included women who been prescribed one of the selective serotonin reuptake inhibitors (SSRIs) – paroxetine, fluoxetine, sertraline, citalopram, or fluvoxamine – or who had had venlafaxine. None of the women whose records were studied had taken duloxetine or escitalopram.

The researchers analysed the records to calculate the effect of taking an antidepressant during tamoxifen treatment, on women’s risk of death from breast cancer after completion of tamoxifen treatment. They adjusted for confounders such as age and duration of tamoxifen treatment.

Women who had taken paroxetine at the same time as tamoxifen had a higher rate of breast cancer mortality during follow-up, and the longer that paroxetine had overlapped with tamoxifen, the greater the increase in mortality. The other SSRIs and venlafaxine had no such effect.

An absolute increase of 25% in the time on tamoxifen for which a woman also took paroxetine led to a 24% increase in breast cancer mortality. A 50% increase in the proportion of time when paroxetine overlapped with tamoxifen led to a 54% increase in breast cancer mortality; and increasing overlap by 75% led to a 91% increase in death from breast cancer.

The authors say that these figures are highly relevant: “We estimate that treatment with paroxetine for 41% of tamoxifen therapy (the median in our study) could result in one additional breast cancer death at five years for every 20 women so treated.”

The conversion of tamoxifen to endoxifen – its most important active metabolite in terms of breast cancer treatment – is catalysed mainly by cytochrome P450 isoenzyme 2D6 (CYP2D6), and paroxetine is an exceptionally potent CYP2D6 inhibitor.

The authors conclude that doctors must take care in selecting an antidepressant for women on tamoxifen: “Our findings indicate that the choice of antidepressant can significantly affect survival in women receiving tamoxifen for breast cancer. This observation is consistent with the critical role of CYP2D6 in the metabolic activation of tamoxifen, and highlights a drug interaction that is extremely common, widely underappreciated and uniformly avoidable.

“Tamoxifen is a crucial element of treatment for patients with hormone receptor positive breast cancer regardless of age or breast cancer stage. When co-prescription of tamoxifen with an antidepressant is necessary, preference should be given to antidepressants that show little or no inhibition of CYP2D6.”

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