(Ivanhoe Newswire) -- A new study finds antidepressants taken to control side effects of the breast cancer drug tamoxifen may hinder the effect of the drug. However, researchers say until larger trials are done the results of this small study should not alter treatment recommendations.

Tamoxifen is a highly effective treatment for women with breast cancer and for those at high risk for breast cancer. Although tamoxifen is generally well tolerated by patients, up to 80 percent of women who take tamoxifen have hot flashes. Up to 45 percent of these women say their hot flashes are severe; therefore it has become common for doctors to give a second prescription to treat this side effect. Several studies have shown selective serotonin reuptake inhibitors, a type of antidepressant, are effective for the treatment of hot flashes. But what happens when a woman takes tamoxifen and an SSRI? Researchers from Georgetown University Medical Center and Indiana University School of Medicine conducted a study to answer that question.

For the study, researchers examined blood samples from 12 women with breast cancer. The women received the SSRI paroxetine for four weeks. Researchers studied the effects of the antidepressant on the enzymes that are responsible for the metabolism of tamoxifen into its active metabolites.

Researchers say the most potent metabolite is 4-hydroxy-tamoxifen. Researchers identified a previously unrecognized active metabolite that was present in higher concentrations than 4-hydroxy tamoxifen in the blood samples. They named this metabolite endoxifen. After paroxetine treatment, endoxifen levels decreased whereas 4-hydroxy-tamoxifen did not. Researchers also looked at the CYP2D6 genotype in the patients. They found the concentrations of endoxifen concentrations decreased by 64 percent in women with a normal CYP2D6 genotype but by only 24 percent in women with a different CYP2D6 genotype. What this means is the antidepressant may interfere with the breakdown of tamoxifen into its active metabolites.

Study authors say while this study raises some questions about the combination treatment of tamoxifen and antidepressants, they say more studies are needed before any conclusions can be made. Doctors from Mayo Clinic agree with this opinion in an accompanying editorial. The Mayo doctors say the clinical implications of reduced levels of endoxifen remains unclear. They point out that newer antidepressants also need to be studied when used in combination with tamoxifen.

SOURCE: Journal of National Cancer Institute, 2003;95:1758-1764, 1734-1735

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