Psy-World

Use of paroxetine during tamoxifen treatment is associated with an increased risk of death from breast cancer.

Up to 25% of patients with breast cancer experience a depressive disorder. Newer antidepressants widely used to treat depression in women with breast cancer are also prescribed for tamoxifen-related hot flashes and other indications. Conversion of tamoxifen to its most important metabolite, endoxifen, is catalysed predominantly by cytochrome P450 isoenzyme 2D6 (CYP2D6). Since selective serotonin reuptake inhibitor (SSRI) antidepressants inhibit CYP2D6, a study explored whether SSRIs may reduce tamoxifen's effectiveness. The study was retrospective and population based, and initially analyzed data from 24,430 women (66 years or older) over a 13-year period. Of these women, 7489 (30.6%) received at least 1 antidepressant during the time they were taking tamoxifen, and there were 2430 women in the primary analysis. Most of these women started taking tamoxifen within a year of their breast cancer diagnosis, and the median duration of tamoxifen treatment was 4 years. The most commonly prescribed antidepressant was paroxetine (in 25.9% of women), followed by sertraline (22.3%), citalopram (19.2%), venlafaxine (15%), fluoxetine (10.4%), and fluvoxamine (7.2%). Older cyclic antidepressants were prescribed in 18.3% of women. By the end of follow-up (mean, 2.38 years), a total of 1074 women (44.2%) had died; breast cancer was recorded as the cause of death in 374 women (15.4%). There was an increased risk of death from breast cancer and death from any cause among women who received paroxetine, an irreversible CYP2D6 inhibitor, in combination with tamoxifen. However, no such risk was present with the other antidepressants. Absolute increases of 25%, 50%, and 75% in the proportion of time on tamoxifen with overlapping use of paroxetine were associated with an increase of 25%, 54%, and 91%, respectively, in the risk for death from breast cancer (p < 0.05 for all comparisons). These findings show that paroxetine can reduce or abolish the benefit of tamoxifen in women with breast cancer and suggest that when co-prescription of tamoxifen with an antidepressant is necessary, preference should be given to drugs that show little or no inhibition of CYP2D6. Kelly CM, Juurlink DN, Gomes T, Duong-Hua M, Pritchard KI, Austin PC, Paszat LF (2010). Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study. BMJ 340:c693. Updated February 2010