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Some Antidepressants May Thwart Tamoxifen's Effect on Breast Cancer

But tamoxifen often causes hot flashes, a side effect that can be controlled with selective serotonin reuptake inhibitor (SSRI) antidepressants such as paroxetine (Paxil) or fluoxetine (Prozac). Besides working on the neurotransmitter serotonin, these drugs inhibit an enzyme called 2D6, necessary to convert tamoxifen into its main active metabolite, endoxifen.

Women who have a gene mutation preventing the formation of 2D6 do not reap the same benefits from tamoxifen as women without the mutation, the researchers noted. Moreover, drugs that inhibit the formation of 2D6 may result in lower levels of endoxifen, although the clinical implications of that remain unclear.

The U.S. Food and Drug Administration is still weighing whether or not to add a caution about the gene variation to the tamoxifen label.

In one of the studies, Medco, a U.S. pharmacy benefits management company, reviewed the medical records of 10.7 million members of a health plan. That analysis turned up 945 women taking tamoxifen and 353 taking tamoxifen plus an SSRI/2D6 inhibitor, most commonly Prozac and Paxil.

Both groups of women, whose average age was in the early 50s, had followed similar treatment courses.

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Pat Elliott

Breast Cancer Guide