« Back

Paroxetine interferes with clinical benefit of tamoxifen therapy, research indicates

Friday, February 19 2010 | Comments

---

What's This? Women with breast cancer who take paroxetine hydrochloride, a selective serotonin uptake inhibitor (SSRI) antidepressant, concomitantly with tamoxifen, a selective estrogen receptor modulator, appear to be more likely to die from the disease than are women who take other SSRIs, according to recently published study results.

Cytochrome P450 isoenzyme 2D6 (CYP2D6) is the primary catalyst that converts the prodrug tamoxifen to the active metabolite endoxifen, which has an affinity for the estrogen receptor that is 100 times greater than the parent compound, the authors explained. While SSRIs inhibit CYP2D6 to varying degrees, paroxetine is a particularly potent inhibitor of CYP2D6, they added.

To test the effect of different SSRIs on tamoxifen's efficacy, the investigators conducted a retrospective, population-based cohort study among 2,430 women (aged >=66 years) who were treated with tamoxifen between Jan. 1, 1993, and Dec. 31, 2005, and had overlapping treatment with a single SSRI. The primary endpoint was risk of death from breast cancer after completing tamoxifen treatment. Cox proportional hazard regression was used to examine the effect of SSRI co-prescribing on survival.

The SSRIs analyzed in the study include paroxetine, fluoxetine hydrochloride, sertraline hydrochloride, citalopram hydrobromide, and fluvoxamine maleate. The serotonin-norepinephrine reuptake inhibitor venlafaxine hydrochloride was also included.

After adjusting for potential confounders, including age and duration of tamoxifen treatment, an absolute increase of 25% in the proportion of time on tamoxifen with overlapping paroxetine was associated with a 24% percent increase in the risk of death from breast cancer (P<.05). Absolute increases of 50% and 75% in the proportion of time on tamoxifen with overlapping paroxetine were associated with increases of 54% and 91% in the risk of death from breast cancer (P<.05 for both).

No such risk was observed with the other antidepressants assessed in the study.

The investigators estimated that the use of paroxetine for 41% of the time on tamoxifen treatment (the median overlap in the study) would result in 1 additional breast cancer death within 5 years of ending tamoxifen treatment for every 19.7 patients thus treated (95% CI, 12.5-46.3).

When the analysis was extended to include death from any cause, the use of paroxetine was again associated with an increased risk of death; however, as in the original analysis, no such increase in the risk of death was seen with the other antidepressants in the study.

"When co-prescription of tamoxifen with an antidepressant is necessary, preference should be given to antidepressants that show little or no inhibition of CYP2D6," the authors concluded. (Kelly CM, et al. BMJ 2010;340;c693.)

Print  |  E-mail