From the Guidelines
When prescribing an SSRI for patients on tamoxifen, escitalopram or citalopram are generally the preferred choices, as they have minimal inhibition of the CYP2D6 enzyme, which is crucial for converting tamoxifen to its active metabolite endoxifen, as noted in the most recent guidelines 1. The choice of SSRI is critical in patients on tamoxifen, as some SSRIs can inhibit the CYP2D6 enzyme, potentially reducing tamoxifen's effectiveness in preventing breast cancer recurrence.
- Fluoxetine and paroxetine should be avoided as they strongly inhibit CYP2D6, potentially reducing tamoxifen's effectiveness in preventing breast cancer recurrence.
- Sertraline has moderate CYP2D6 inhibition and should be used cautiously.
- For patients requiring antidepressant treatment while on tamoxifen, escitalopram (10-20 mg daily) or citalopram (20-40 mg daily) represent the safest options, as they have minimal impact on tamoxifen metabolism, as supported by recent guidelines 1.
- Venlafaxine (a SNRI) is another good alternative with minimal CYP2D6 interaction, as noted in previous studies 1. This drug interaction concern is particularly important because reduced tamoxifen efficacy could impact cancer outcomes, highlighting the need for careful consideration of SSRI selection in patients on tamoxifen, as emphasized in recent guidelines 1. When initiating these medications, start at lower doses and monitor for both therapeutic effect and side effects, adjusting as needed while maintaining the focus on preserving tamoxifen's anticancer activity.
From the Research
SSRI of Choice with Tamoxifen
- The choice of SSRI with tamoxifen is crucial due to potential interactions between the two medications 2, 3.
- Some SSRIs, such as paroxetine and fluoxetine, are strong inhibitors of CYP2D6 and should be avoided in patients receiving tamoxifen 2.
- Other SSRIs, such as citalopram, desvenlafaxine, escitalopram, milnacipran, and venlafaxine, are recommended as they do not significantly influence the metabolism and clinical efficacy of tamoxifen 2, 4.
- Studies have shown that citalopram has limited potency to inhibit CYP2D6 activity and can be used in breast cancer patients taking tamoxifen without adversely affecting the outcome of adjuvant therapy 3.
- However, a prospective trial found that the addition of venlafaxine or citalopram to tamoxifen treatment decreases plasma Z-endoxifen concentrations, although the clinical significance of this interaction is unclear 4.
- A systematic review of studies comparing endocrine therapy alone or concurrent with antidepressants in breast cancer patients found no consistent evidence that concurrent use of antidepressants with tamoxifen therapy has negative impacts on clinical outcomes 5.
Recommended SSRIs
- Citalopram 2, 3, 4
- Desvenlafaxine 2
- Escitalopram 2
- Milnacipran 2
- Venlafaxine 2, 4
- Sertraline 2
- Bupropion 2
- Duloxetine 2