Interactions Between Tamoxifen and Antidepressants via Cytochrome P450 2D6

Objective: Women taking tamoxifen for the treatment or prevention of recurrence of breast cancer are likely to take antidepressants either for a psychiatric disorder or for hot flashes. Recent evidence suggested that some antidepressants inhibit the metabolism of tamoxifen to its more active metabolites by the cytochrome P450 2D6 (CYP2D6) enzyme, thereby decreasing the anticancer effect. This article reviews the literature on the interactions between newer antidepressants and tamoxifen via CYP2D6 and offers treatment recommendations.

Data Sources: A literature search of clinical and nonclinical studies published prior to September 2008 was conducted on PubMed. We performed 3 different searches combining the terms tamoxifen and SSRIs; tamoxifen and CYP2D6 inhibitors; and antidepressant and breast cancer recurrence. A fourth search with CYP2D6 inhibition and the generic names of individual antidepressants was carried out.

Study selection: Seven clinical research articles were selected. Nonclinical research articles about antidepressants were included if they mentioned in vitro or in vivo inhibition of CYP2D6.

Data Synthesis: There is consistent evidence that paroxetine and fluoxetine have a large effect on the metabolism of tamoxifen and should not be used. Indirect evidence indicates that bupropion may also have a large effect on the metabolism of tamoxifen. Venlafaxine has little or no effect on the metabolism of tamoxifen and may be considered the safest choice of antidepressants. Desvenlafaxine is not metabolized by the P450 system and may consequently be another option. Mirtazapine has not been extensively studied, but existing research suggests minimal effect on CYP2D6. The remaining commonly prescribed antidepressants have mild to moderate degrees of CYP2D6 inhibition.

Conclusions: Clinicians treating patients with breast cancer should review the prescription profiles of their patients to evaluate the need for treatment modification. There are safe options for the treatment of depression and clinicians and patients should bear in mind the health risks of untreated depressive states.

Submitted: November 2, 2008; accepted March 27, 2009.

Corresponding author: Julie Desmarais, MD, McGill University, Research and Training Building, 1033 Pine Avenue West, Room 107, Montreal, Quebec, Canada H3A 1A1 ([email protected]).