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.


METHODS
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.


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


RESULTS
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.
Department of Psychiatry, McGill University, Montreal, Quebec, Canada. julie.desmarais@mail.mcgill.ca
Julie Eve
JE
Desmarais
Karl J
KJ
Looper
D000928:Antidepressive Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016642:Bupropion / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D003511:Cyclohexanols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D019389:Cytochrome P-450 CYP2D6 / Q000187:drug effects / Q000378:metabolism*; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism*; D004347:Drug Interactions; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics; D013629:Tamoxifen / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000069470:Venlafaxine Hydrochloride
D000928:Antidepressive Agents; D016642:Bupropion; D003511:Cyclohexanols; D019389:Cytochrome P-450 CYP2D6; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D003577:Cytochrome P-450 Enzyme System; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors; D013629:Tamoxifen; D000069470:Venlafaxine Hydrochloride