Since it received FDA approval in 1977, tamoxifen has reduced breast cancer recurrences by one-half and breast cancer deaths by one-third in women with early-stage estrogen receptor-positive breast cancer. Unfortunately, the drug does not benefit every woman who takes it.
One reason is genetic. The liver uses the cytochrome P450 enzymes to metabolize many drugs. One of them, CYP2D6, is the principal enzyme that converts tamoxifen into endoxifen, a form that is active in the body. Variations in the gene that synthesizes CYP2D6 can limit women's ability to convert tamoxifen into its active form; about 7% of women have no CYP2D6 activity.
But drug interactions also contribute — an important consideration for mental health clinicians, as approximately 20% to 30% of the women who take tamoxifen also use antidepressants to alleviate depression, anxiety, or hot flashes. Some antidepressants are such strong inhibitors of CYP2D6 that women who take these drugs may not benefit from tamoxifen. Two papers suggest that three antidepressants — paroxetine (Paxil), fluoxetine (Prozac), and bupropion (Wellbutrin) — are most likely to inhibit CYP2D6 and interfere with tamoxifen treatment.
In one paper, researchers at McGill University reviewed seven clinical studies of women taking both tamoxifen and antidepressants. They also examined laboratory studies to assess the inhibitory effects of various antidepressants on the CYP2D6 enzyme in cell cultures. They found consistent evidence that two selective serotonin reuptake inhibitors (SSRIs) — paroxetine and fluoxetine — were strong inhibitors of CYP2D6. Indirect evidence from the laboratory studies suggested that bupropion, an antidepressant that affects the neurotransmitters norepinephrine and dopamine, also severely inhibits CYP2D6. Other drugs had less of an impact on this enzyme (see table).
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Originally Posted by king6 II
