Antidepressants lower effectiveness of Chemotherapy

Antidepressants Cut Effectiveness of Tamoxifen in Breast Cancer

By Lisa Rapaport

May 30 (Bloomberg) — Tamoxifen, a breast cancer medicine used by millions of women, doesnt work when taken with antidepressants like Eli Lilly & Co.s Prozac, Pfizer Inc.s Zoloft and GlaxoSmithKline Plcs Paxil, a study says.

Tumors were more than twice as likely to return after two years in women taking the antidepressants while on the cancer drug, compared with those taking tamoxifen alone, the study showed. The research, by Medco Health Solutions Inc., was presented today at a meeting of the American Society of Clinical Oncology in Orlando.

Doctors began treating hot flashes with antidepressants, an unapproved use, after a U.S. study seven years ago linked the former standard remedy, hormone replacement therapy, to an increased risk of breast cancer and heart attacks. Other types of antidepressants, such as Wyeths Effexor, may be safer for women on tamoxifen than Paxil or Prozac, said Powel Brown, director of cancer prevention at the Lester and Sue Smith Breast Cancer Center at Baylor College of Medicine in Houston.

Effexor doesnt interfere with tamoxifen so that is the preferred drug for oncologists to treat hot flashes, said Brown, who wasnt involved in the study. We need to get that message out to primary care doctors and psychiatrists and gynecologists so they will be aware that antidepressants like Paxil have a risk of inhibiting tamoxifen.

Hot flashes are a side effect of tamoxifen.

Breast cancer is the second most common malignancy in women, after skin tumors, according to the Atlanta-based U.S. Centers for Disease Control and Prevention. About 187,000 women were diagnosed with breast cancer and 41,000 women died from it in 2005, the most recent year for which CDC data are available.

Tumor Fighter Enzyme

Tamoxifen cant combat tumors until it mixes inside the body with a liver enzyme called CYP2D6 to morph into an active tumor fighter called endoxifen. Many antidepressants use the same enzyme, sapping supplies needed for tamoxifen to do its work.

The patient might as well be taking a placebo, said Frankie Ann Holmes, associate director of breast cancer studies at U.S. Oncology Research in Houston, in a 2005 report published by ASCO. Holmes said antidepressants known as selective serotonin reuptake inhibitors, or SSRIs, shouldnt be used in patients taking tamoxifen.

SSRIs include Paxil and Prozac, and Zoloft, as well as Forest Laboratories Inc.s Celexa and Lexapro. Paxil is the strongest in blocking availability of the CYP2D6 enzyme, Holmes found.

In the study presented today, Medco searched medical and pharmacy records of 10.7 million people to see what happened to women taking tamoxifen along with antidepressants known to interfere with the CYP2D6 enzyme.

Twice the Risk

After two years, patients taking both SSRIs and tamoxifen had a 14 percent risk of tumors recurring, compared with 7.5 percent for women taking the cancer drug alone. The risk increased to 16 percent among those using Paxil, Prozac or Zoloft, the data showed.

The study included 945 women on tamoxifen, and an additional 353 also using an antidepressant.

This is the first large outcomes-based study to reinforce earlier research questioning the use of Paxil and Prozac in patients taking tamoxifen, said Robert Epstein, a study author and chief medical officer for Medco, a pharmacy benefits company based in Franklin Lakes, New Jersey.

Medco Warning

Medco warns pharmacists to check with doctors before filling prescriptions for SSRIs if women are also taking tamoxifen, Epstein said. We would encourage doctors to consider an alternative if there is an option that would also address hot flashes or depression without interfering with tamoxifen, he said.

Outside science advisers to the U.S. Food and Drug Administration in Oct. 2006 reviewed the potential for certain antidepressants to render tamoxifen ineffective.

The committee of scientists concluded that information on this drug interaction should be added to tamoxifens label. The current label doesnt have any statements about this risk.

FDA spokeswoman Rita Chappelle didnt immediately respond to a telephone message seeking comment.

To contact the reporter on this story: Lisa Rapaport in New York at
Last Updated: May 30, 2009 15:45 EDT

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