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article imageUpdate: Tamoxifen Benefits Compromised by More than Just Paxil Special

article:287454:6::0
By Caroline Menzies     Feb 12, 2010 in Health
In a recent study, the antidepressant, paroxitine (Paxil), was found to nullify the benefits of the breast cancer drug, Tamoxifen. Other antidepressants found to have no effect on Tamoxifen in the study may be suspect anyway, lead researcher says.
A recent study conducted at the Institute for Clinical Evaluative Sciences (ICES) in Toronto on the effects of antidepressants know as selective serotonin reuptake inhibitors, (or SSRIs) on the life saving drug tamoxifen, found that women taking Paxil while they are also taking tamoxifen, would not be gaining any benefit from the tamoxifen (as reported in this article).
Despite the fact that the other antidepressants looked at in the study seemed to have no noticeable effect on tamoxifen, Dr. Catherine Kelly, the lead researcher and author of the study, said the number of women in the study taking other antidepressants wasn't large enough to determine a negative effect on tamoxifen treatment, but there is sufficient prior knowledge of their effects on tamoxifen to recommend changing to a safer alternative.
Dr. Kelly, from the Department of Breast Medical Oncology at The University of Texas M.D. Anderson Cancer Center said,
In our study we found (the) use of paroxetine but not other SSRIs in combination with tamoxifen was associated with an increased long term risk of breast cancer mortality that correlated with the extent of drug overlap.
We also looked at fluoxetine and although this too is a potent CYP2D6 inhibitor we did not find a similar increase in risk. However, this may be because we did not have enough women exposed to this drug in our study to answer this question.
It would be reasonable at this time to avoid antidepressants that are potent CYP2D6 inhibitors during tamoxifen therapy (paroxetine, fluoxetine and bupropion). Venlafaxine and citalopram are considered weak inhibitors and could be considered as reasonable alternatives. It is also extremely important that any changes in medication are under the close supervision of a physician.
Tamoxifen works in hormone sensitive breast cancers by being converted by an enzyme in the liver, called CYP2D6, to active metabolites, which suppress the estrogen feeding the tumour. Antidepressants that are strong, or moderate inhibitors of CYP2S6 are not recommended to be taken while taking tamoxifen. Mild inhibitors are thought to be safe.
Strong inhibitors include the antidepressants, paroxetine (Paxil, Seroxat), fluoxetine (Prozac, Sarafem), bupropion (Wellbutrin, Zyban); moderate inhibitors include sertraline (Zoloft), while mild inhibitors include venlafaxine (Effexor). Venlafaxine is an SNRI (not an SSRI) and it has little or no CYP2D6 inhibitory activity, Citalopram (Celexa) is considered a weak CYP2D6 inhibitor. The latter two are considered safe antidepressants to take with tamoxifen.
Dr. Kelly provided this link from Indiana University and the Consortium on Breast Cancer Pharmacogenomics for more detailed information.
When asked about other current or planned studies in this area, she said,
Other large research groups are conducting studies similar to ours so we would expect more data in the near future, in addition many groups are studying genetic alterations in CYP2D6 in women taking tamoxifen.
article:287454:6::0
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