Women receiving tamoxifen for the treatment or prevention of breast cancer should be aware of possible drug-drug interactions with specific antidepressant medications (e.g., SSRI). These antidepressants are used widely to treat depression and anxiety disorders. In addition, multiple studies have shown that these antidepressants are an effective non-hormonal treatment for hot flashes; over 25% of women who are experiencing hot flashes related to tamoxifen therapy are now prescribed antidepressants to manage their symptoms.
Tamoxifen is a SERM (selective estrogen receptor modulator) used for the treatment of breast cancer. It reduces relapse rates of breast cancer and increases overall survival. Tamoxifen is also used to reduce the risk of breast cancer in women at high risk for the disease. Tamoxifen’s effects in the breast depend on its ability to antagonize estrogen. Tamoxifen’s anti-estrogen affinity is thought to depend on the activity of its primary metabolite, endoxifen. Tamoxifen is metabolized to endoxifen through the liver enzyme CYP2D6. Consequently, any co-administered agent that inhibits this enzyme will reduce the conversion of tamoxifen to endoxifen, thereby potentially reducing the efficacy of tamoxifen as a breast cancer therapy (Jin et al, 2005). Many commonly used antidepressants are CYP2D6 inhibitors, thus clinicians and patients must consider possible interactions when using these treatments in women taking tamoxifen.
In several studies (notably, Jin et al, 2005), concurrent use of tamoxifen with the potent CYP2D6-inhibitor antidepressants paroxetine and fluoxetine, was associated with a significant reduction in circulating endoxifen levels in some women. Based on current research, the psychotropic medications which are the strongest CYP2D6 inhibitors include paroxetine, fluoxetine, buproprion, duloxetine, while sertraline, escitalopram, and doxepin are moderate inhibitors, and venlafaxine is a weak inhibitor.
In 2006, an FDA advisory committee debated if the label for tamoxifen should include information about increased risks based on CYP2D6 metabolism. The subcommittee recommended that the label should be updated to reflect an increased risk of treatment failure when tamoxifen is co-administered with potent CYP2D6 inhibitors.
Strong Inhibitors (Should be avoided if possible):
Weak Inhibitors (Use not restricted by treatment with tamoxifen):
If antidepressants are indicated in the treatment of a woman currently taking tamoxifen, the following treatment recommendations have been made:
- If possible, avoid antidepressants, including fluoxetine and paroxetine, that are strong inhibitors of the CPY2D6 enzyme (see the list of inhibitors above)
- If the antidepressant is being used solely for the management of hot flushes, other agents, such as gabapentin, may be used instead
- If it is not possible to avoid these antidepressants, another option for postmenopausal women only would be to switch from tamoxifen to an aromatase inhibitor, if medically appropriate
Erica Pasciullo, BA
Hadine Joffe, MD, MSc
Drug-Drug Interactions, specifically with CPY2D6 enzyme: University of Indiana Division of Clinical Pharmacology
Memo to the Media in the Journal of the National Cancer Institute
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