Popular antidepressant blocks the beneficial effects of tamoxifen in breast cancer
Research: Selective serotonin reuptake inhibitors and breast
cancer mortality in women receiving tamoxifen: a population based
cohort study) http://www.bmj.com/cgi/doi/10.1136/bmj.c693
(Editorial: Interaction of serotonin reuptake inhibitors with
tamoxifen) http://www.bmj.com/cgi/doi/10.1136/bmj.c783
LONDON, Feb. 11, 2010--Women with breast cancer who take the
antidepressant paroxetine at the same time as tamoxifen are at an
increased risk of death, concludes a study published on bmj.com
today.
However, the authors stress that their results should not lead
patients to stop taking tamoxifen, and do not imply that paroxetine
itself causes or influences the course of breast cancer. "This is
simply a situation in which paroxetine impairs the effectiveness of
tamoxifen," they explain.
Breast cancer is the most commonly diagnosed cancer in women
worldwide and the drug tamoxifen significantly improves survival.
In order to work, however, tamoxifen must be converted into an
active metabolite (endoxifen) by the liver.
But some drugs can interfere with this process. Antidepressants are
of particular importance because they are commonly used in women
with breast cancer, often for long periods of time. Although many
antidepressants have little or no impact on tamoxifen's metabolism,
paroxetine, a member of the selective serotonin reuptake inhibitor
(SSRI) class of drugs, is a potent inhibitor of the metabolic step
that converts tamoxifen to endoxifen.
So Dr Catherine Kelly and colleagues at the Institute for Clinical
Evaluative Sciences (ICES) in Toronto set out to investigate
whether SSRIs can reduce tamoxifen's effectiveness in
practice.
They examined the healthcare records of 2,430 women aged 66 years
or older with breast cancer who received tamoxifen between 1993 and
2005. About 30% of these women also received an antidepressant at
some time during their treatment with tamoxifen, and paroxetine was
the most commonly used agent.
The results show that use of paroxetine, but not other SSRIs, in
combination with tamoxifen, was associated with an increased
long-term risk of breast cancer death, in a fashion that correlated
with the extent of drug overlap.
This supports the theory that paroxetine can reduce or abolish the
benefit of tamoxifen in women with breast cancer.
The researchers estimate that treatment with paroxetine for 41% of
the total time on tamoxifen (the median in this study) will result
in one additional breast cancer death at five years for every 20
women so treated. The risk with more extensive overlap is
greater.
"Our findings indicate that the choice of antidepressant can
significantly influence survival in women receiving tamoxifen for
breast cancer," says Dr David Juurlink, one of the study's authors
and a scientist at ICES. "This observation is consistent with what
we know about tamoxifen's metabolism. These results highlight a
drug interaction that is extremely common, widely underappreciated
and potentially life-threatening, yet uniformly avoidable."
"Tamoxifen is a crucial element of therapy for patients with
hormone receptor-positive breast cancer regardless of age or breast
cancer stage," he adds. "When co-prescription of tamoxifen with an
antidepressant is necessary, preference should be given to
antidepressants that exhibit little or no impact on tamoxifen's
metabolism."
In an accompanying editorial, Frank Andersohn and Stefan Willich
from Charité University Medical Center in Berlin say that
clinicians should avoid co-prescribing paroxetine and tamoxifen in
women with breast cancer, but warn against abrupt withdrawal of
SSRI treatment.
They also call for this potential interaction to be made clear on
all products containing tamoxifen and paroxetine, and for its
promotion amongst physicians and pharmacists.
Contacts:
Research: David Juurlink, Division Head, Clinical Pharmacology and
Toxicology, Sunnybrook Health Sciences Centre, Toronto, Ontario,
Canada Email:
david.juurlink@ices.on.cadavid.juurlink@ices.on.ca> Editorial:
Frank Andersohn, Senior Research Associate, Institute for Social
Medicine, Epidemiology, and Health Economics, Charité
University Medical Center, Berlin, Germany Email:
frank.andersohn@charite.de
Posted: February 2010
