Concomitant Use of Antidepressant Drugs and Tamoxifen

ABSTRACT Disclosure All authors have declared no conflicts of interest. The CYP2D6 enzyme is primarily involved in the metabolism of tamoxifen into its most important metabolite endoxifen. The efficacy of tamoxifen therapy may be influenced by genetic polymorphisms of this enzyme and CYP2D6-inhibiting co-medication (e.g. antidepressant drugs). It is therefore generally recommended to avoid potent CYP2D6 inhibitors (e.g. paroxetine, fluoxetine) in tamoxifen patients. In this study, we examined whether women using tamoxifen still received strong CYP2D6-inhibiting antidepressants concomitantly during the period 2005-2010. Drug dispensing data for tamoxifen and seven antidepressants associated with CYP2D6 inhibition (paroxetine, fluoxetine, sertraline, fluvoxamine, (es)citalopram and venlafaxine), were obtained from the community pharmacy database of the PHARMO Institute. This database contains dispensing data of > 3 million people in the Netherlands. Concomitant use of CYP2D6-inhibiting antidepressants in women using tamoxifen, as well as the use of antidepressants in the total population, were determined per year using PASW Statistics 17.0 (SPSS Inc., Chicago, IL). Prevalence of the use of the four most common antidepressants among tamoxifen users, expressed as the number of women receiving an antidepressant concurrently with tamoxifen per 1000 tamoxifen users, is shown in the table. Although there is a downwards trend for paroxetine, this drug is still one of the most frequently used antidepressants in tamoxifen patients. In addition, a similar trend was observed in the total population of the database. Venlafaxine and citalopram, associated with weak CYP2D6-inhibiting properties, are increasingly co-prescribed. 2005 2006 2007 2008 2009 2010 Paroxetine 47.1 44.3 46.6 41.7 36.9 28.8 Fluoxetine 9.5 10.6 9.8 10.7 10.8 9.7 Citalopram 17.0 23.5 22.4 26.2 25.2 28.5 Venlafaxine 18.3 23.8 28.2 27.5 29.1 30.8 Despite the strong biological rationale to avoid potent CYP2D6-inhibiting co-medication in tamoxifen treated patients, paroxetine is still often used along with tamoxifen. In clinical practice, one should be extremely alert to co-medication in these patients. It is advised that strong CYP2D6 inhibitors are switched to weaker CYP2D6-inhibiting alternatives, if possible.