The longer the women in the study took the widely prescribed breast cancer drug with Paxil, the greater their risk of death.
None of the women in the study took Wellbutrin and not enough took Prozac to show an effect, study co-author David N. Juurlink, MD, PhD, tells WebMD.
But he says women who are taking tamoxifen should probably avoid all three drugs.
"There is a good pharmacologic reason to believe these drugs should not be used," he says. "Tamoxifen users who are already on one of these drugs should consider switching to another antidepressant, but this has to be done gradually."
Why Tamoxifen's Power May Be Weakened
Juurlink says the three drugs inhibit the ability of a key enzyme in the liver, known as CYP2D6, to convert tamoxifen to its active tumor-fighting form.
Tamoxifen is used to suppress the estrogen that fuels tumor growth in some breast cancers. Antidepressants are widely prescribed to lessen common tamoxifen-related side effects, including hot flashes.
In a study reported last summer at the annual meeting of the American Society of Clinical Oncology, three selective serotonin reuptake inhibitor (SSRI) antidepressants -- Paxil, Prozac, and Zoloft -- were linked to an increased risk of breast cancer recurrence in tamoxifen users.
Women in the study who took tamoxifen with one of the drugs had twice the risk of having their cancer come back as women who did not take an SSRI.
Erik Stanek, PharmD, who worked on the study, tells WebMD that it is increasingly clear that SSRIs that are moderate to potent CYP2D6 inhibitors should not be prescribed with tamoxifen.
Stanek is senior director for research with the New Jersey-based health benefits company Medco Health Solutions.
"When you consider all the research together there is some disagreement, but a great deal of concordance that drugs that are weak 2D6 inhibitors or don't interact at all are better choices."
In the newly published study, Juurlink and colleagues analyzed the medical records of 2,430 women with breast cancer who took tamoxifen for an average of about four years between 1993 and 2005.
About 30% of the women also took an SSRI at some point while taking tamoxifen. Paxil was the most widely prescribed antidepressant, followed by Zoloft and Celexa.
Treatment with Paxil for 41% of the time on tamoxifen, which was the average length of overlap, was found to result in one extra breast cancer death for every 20 women treated over five years of follow-up.
The study appears in the journal BMJ.
Antidepressant Options for Tamoxifen Patients
In an editorial accompanying the study, Frank Andersohn, MD, of Berlin's Charite University Medical Center, writes that antidepressants with a low potential to inhibit CYP2D6, such as the SSRIs Effexor and Celexa, are clearly the drug of choice for patients on tamoxifen.
"The risk is probably not that great with any SSRI taken for a few weeks or months," he tells WebMD. "But it is clear that for long-term use with tamoxifen, Paxil and Prozac should be avoided."
When breast cancer survivor Courtney Bugler went on tamoxifen four years ago following treatment at age 29, she knew pretty quickly she needed something to deal with the hot flashes and other side effects that made her miserable and kept her up at night.
"I was on fire all the time. I couldn't sleep and was getting really cranky," she tells WebMD. "My doctor was emphatic that Effexor was the only SSRI I should be on. And I can honestly say that it changed my universe. I was on a baby dose, but it was enough to take the edge off the hot flashes and help me sleep at night."
Bugler, who is now executive director of the Atlanta affiliate for the breast cancer support group Young Survival Coalition, says the topic of which antidepressants are OK with tamoxifen and which are not gets a lot of attention on breast cancer message boards.
"This is not a really big problem for patients like me who take antidepressants for tamoxifen-related side effects," she says. "But it is a big deal for patients taking Paxil or Prozac for depression, especially if these are the drugs that work best for them."
A spokeswoman for the pharmaceutical company GlaxoSmithKline, which markets Paxil, tells WebMD that in 2008 the company updated the drug's label to warn that taking Paxil with tamoxifen may reduce tamoxifen's effectiveness.
"GlaxoSmithKline will review the additional data published this week and will work with regulatory agencies to determine the next steps," Sarah Alspach, GlaxoSmithKline's director of U.S. corporate media, notes in a statement.