Antidepressant blocks tamoxifen benefit, may raise cancer death risk: study

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TORONTO - Women prescribed tamoxifen to prevent a recurrence of breast cancer should avoid taking the antidepressant Paxil and its generic equivalents because of a potentially dangerous drug interaction, a study suggests.
Paxil, or paroxetine as it is known generically, appears to negate the effects of tamoxifen, and may lead to an increased risk of death from breast cancer, the researchers say.
Tamoxifen is prescribed as a treatment and preventive therapy for estrogen receptor-positive breast cancer and works by blocking the effects of the hormone.
"Tamoxifen is a hall of fame chemotherapy agent," said Dr. David Juurlink, a co-author of the study published in this week's issue of the British Medical Journal.
"It imparts tremendous survival benefits and paroxetine simply deprives the patient of those," explained Juurlink, a scientist at the Institute for Clinical Evaluative Sciences in Toronto. "It takes that benefit away by interfering with the body's normal handling of tamoxifen."
To conduct the study, researchers at ICES analyzed health and prescription records for 2,430 Ontario women aged 66 to 75 who were treated with tamoxifen between 1993 and 2005 to prevent breast cancer recurrence.
The women were also taking antidepressant medications known as selective serotonin re-uptake inhibitors, or SSRIs. They included such popular drugs as paroxetine (Paxil), fluoxetine (Prozac), and sertraline (Zoloft). SSRIs are typically prescribed for women on tamoxifen to treat depression and anxiety or to reduce hot flashes, a common side-effect of tamoxifen.
Paroxetine, taken by more than a quarter of the women in the study, had a negative effect on survival that the other SSRIs appeared not to share, the researchers determined.
"What we found was that using paroxetine ... in combination with tamoxifen increased the risk of death due to breast cancer," said Juurlink. "And it did that in a fashion that corresponded with the degree of overlap. So the more of your tamoxifen time that you received paroxetine, the higher the risk."
The average patient in the study had a 41 per cent overlap, he said, meaning that for 41 per cent of the time they were taking tamoxifen, they were also on paroxetine.
The researchers estimate that taking both drugs for that length of time results in one extra death from recurrent breast cancer at five years for every 20 women so treated. That risk increases to one extra death for every seven women if both drugs are taken for 100 per of the treatment window.
"If people are taking paroxetine with tamoxifen, I think there's a strong argument to be made for transitioning to a different antidepressant," Juurlink said.
"What people should not do is stop the tamoxifen, and they would not be advised to stop their paroxetine suddenly because that's got its own set of problems (withdrawal syndrome)," he said, advising that women speak to their doctors.
Juurlink also noted that while the study did not find a higher risk of death from breast cancer among women who took Prozac and Wellbutrin (bupropion), both drugs are known to interfere with the metabolism of tamoxifen and likely should also be avoided.
Dr. Steven Narod, director of the Familial Breast Cancer Research Unit at Women's College Hospital in Toronto, called the study "a really good paper ... I think it's really important."
"Is it proof? No. But it's certainly strongly suggestive," said Narod, who was not involved in the study. "I don't think Paxil increases your chances of dying from breast cancer, it's that it wipes out the benefit of tamoxifen. It indirectly increases risk, it's not carcinogenic."
But he worries lay people could seriously misinterpret the results and conclude "tamoxifen is not a good drug."
"Tamoxifen is an extremely beneficial drug. Tamoxifen in elderly women with ER-positive cancer is extremely effective. It cuts down the risk (of recurrence) by half."
Dr. Karen Gelmon, an oncologist at the B.C. Cancer Agency, was cautious in her assessment of the paper.
Previous studies over the last several years have suggested that some SSRIs, including Paxil and Prozac, may interfere with the body's ability to metabolize tamoxifen, while other research shows no association, she said Monday from Vancouver.
"So the bottom line is this is all pretty interesting, but it's not clear," Gelmon said. "It's not the final word. This is a moving field."
And because of the way the study was performed - analyzing what's known as retrospective data from health records - "there may be other events which interfere that we don't know about."
For instance, the study can't say whether the women were religious in adhering to their daily tamoxifen regimen, said Gelmon, noting that up to 40 per cent of women don't take their medication as prescribed.
However, she agreed doctors should consider trying another SSRI for women on tamoxifen who need an antidepressant, such as Celexa (citalopram) or Effexor (venlafaxine), which appear not to block the anti-cancer drug's effects.

Organizations: College Hospital in Toronto, British Medical Journal, Institute for Clinical Evaluative Sciences ICES Familial Breast Cancer Research Unit B.C. Cancer Agency Celexa

Geographic location: TORONTO, Ontario, Vancouver

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