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Common Antidepressants’ Impact on Effectiveness of Tamoxifen

8/2/2020

I'd like to share with you the results of a similar study that we performed at a Leiden University Medical Center in the Netherlands, and I'll start off with a short introduction on Tamoxifen.

We have known that this drug, which has been used for several decades, to be very effective in treating breast cancer. However, there's still a substantial part of patients, who will get a disease recurrence, despite their treatment with Tamoxifen.

Tamoxifen itself is a pro-drug in this little effective of itself and is metabolized by the enzyme sip26 to endoxifen, which is nowadays considered the most active and most potent metabolite, but based on in vitro data.

Common Antidepressants’ Impact on Effectiveness of Tamoxifen

These sip26 inhibiting drugs can inhibit the activity of sip26 leading to decrease in induction levels. We hypothesize that this will lead to a decrease in your Tamoxifen efficacy and increase in breast cancer recurrences. So, these are the inhibitors, that we are looking at most important inhibitors, are paroxetine and fluoxetine. And the importance is stressed by the fact that these types of drugs are commonly prescribed in up to 30% of breast cancer patients using Tamoxifen in US populations.

Other drugs are cardiac medications, but paroxetine and fluoxetine are a most commonly prescribed.

So, we did the study to assess the safety Tamoxifen treatment, but also to illustrate the importance of Tamoxifen adherence, because only one study linked bad adherence to an increase in overall, an increase in mortality or cause.

So, we looked at nearly 2,000 patients, who use Tamoxifen in the actual treatment setting. And we use three different databases to look at that. We looked at concomitant 6 2016 ever use and Tamoxifen related this to breast cancer recurrences, which were defined in a pathology database or as in a hospital admission database.

So, what we did find is that 11% of these around 2,000 patients used a 76 inhibitor concomitant and 8% were frequent users. So, the mean duration of the use of Tamoxifen was two and a half years and 50% of that time a patient was also using a sip26 inhibitor, mostly paroxetine and fluoxetine. And, surprisingly, we could not find any increased risk for breast cancer recurrence in patients using sip26 inhibitors.

So, these are the results for adherence in our general breast cancer Dutch population. We found a mean adherence of 93%. And we did relate this to breast cancer recurrence, and as we had expected, we found a reduced risk for breast cancer recurrence in patients who had Tamoxifen adherence. This was statistically significant. There was a 27% reduced risk in patients, who were good adherence.

So, concluding we could not detect any hazard after concomitant sip26 inhibitor use. What's another important message is that it seems only sensible to improve to maximum adherence and to set up clinical strategies to improve this adherence to decrease breast cancer recurrences and, maybe, even breast cancer mortality.

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