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Antidepressants counteract tamoxifen’s recurrence-prevention effects

Tamoxifen is an important medication used to help prevent recurrence of breast cancer.
To work in the body, tamoxifen must be changed into a new molecule called endoxifen
by an enzyme in the liver. The enzyme, called CYP4502D6 is genetically deficient in a
minority of women, and these women do not get any benefit from using tamoxifen.
Animal studies and laboratory studies in the past have indicated that some antidepressant
drugs inhibit the action of this enzyme, even in women who have normal levels. When
this enzyme’s activity is inhibited, it cannot make endoxifen. The particular
antidepressants are the SSRIs or selective serotonin uptake inhibitors (this group includes
popular antidepressants such as Paxil and Prozac). Scientists have thought for some time
that these antidepressants might actually counteract the recurrence-preventing effects of
tamoxifen, and this has recently been confirmed in a study presented at the 2009
American Society of Clinical Oncology meeting.
Scientists searched a database of over 10 million patients to find women who used
tamoxifen with or without SSRI antidepressants between 2003 and 2005. The women
had to have used tamoxifen regularly for at least two years. They found 945 women who
used tamoxifen alone and 353 who used it together with an antidepressant that suppressed
CYP4502D6. The number of women in the two groups who had breast cancer recurrences
was then analyzed. The women taking tamoxifen alone had a 7.5% recurrence rate while
the women taking it with antidepressants had a 13.9% recurrence rate – nearly twice the
number of recurrences of the tamoxifen-only group. This strongly implicates the SSRI
antidepressants as having a negative drug interaction with tamoxifen.
This drug interaction is especially problematic for tamoxifen patients since SSRI drugs
have been found to reduce the hot flashes that are often a vexing side effect of tamoxifen,
and many women have been prescribed SSRI drugs for this purpose. The new study
makes this drug combination quite problematic, and women taking SSRI drugs for their
tamoxifen-related hot flashes should contact their physicians to discuss their situation.
There are other antidepressants or other types of drugs that may also be effective at
reducing hot flashes without this drug interaction. Additionally, the Block Center can
also provide a full integrative therapy plan using non-pharmacological as well as
appropriate drug therapies to counter side effects of drugs related to cancer treatment,
including the depression that accompanies some cancer drugs, without causing negative
drug interactions. An example of integrative therapies for hot flashes is acupuncture
while depression and other distress can be effectively treated with cognitive-behavioral
Aubert RE et al. Risk of breast cancer recurrence in women initiating tamoxifen with
CYP3D6 inhibitors. Presented at: American Society of Clinical Oncology Annual
Meeting, May 30, 2009. J Clin Oncol. 27:18s, 2009 (suppl; abstr CRA508).
To summarize: Some types of antidepressant drugs (the selective serotonin reuptake
inhibitors or SSRI’s) have been implicated in a negative drug interaction with tamoxifen,
a medication used to help prevent breast cancer recurrence. These drugs prevent
tamoxifen from being activated in the body. Women taking antidepressants and tamoxifen should consult their doctors about their particular circumstance.



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