On Tamoxifen? Beware of Some Anti-depressants – but only in 7%

Certain anti-depressants are used in chronic pain because of their painkiller effects.

Women with prior Ca. of Breast can end up on a drug called tamoxifen to help prevent recurrences. Tamoxifen has to be convered in the body by a system called cytochrome CYP2D to a drug called endoxifen. Certain anti-depressants inhibit this conversion. A recent article suggests this is can make tamoxifen more ineffective.

Pharmacogenetics: From Description to Prediction
Wendell W. Weber, MD, PhD
Clin Lab Med 28 (2008) 499–511He states:
Poor metabolizer women are predisposed to higher recurrence rates of breast cancer because they produce lower levels of anticancer tamoxifen metabolite, endoxifen. [15]”

[15] Hayes DF, Stearns V, Rae J, et al. A model citizen? Is tamoxifen more effective than the aromatase inhibitors if we pick the right patients? J Natl Cancer Inst 2008;100:610–3

full article here

“Women taking tamoxifen should avoid taking drugs (eg, SSRIs) that inhibit CYP2D6. SSRIs such as venlafaxine are preferred treatment of hot flashes because they do not inhibit CYP2D6; paroxetine and fluoxetine should be avoided because they are potent inhibitors of CYP2D6.”

That means Paxil and Prozac (and fluvoxamine = Luvox) are bad. Duloxetine (Cymbalta) and bupropion (Wellbutrin – aka Zybam) are moderate inhibitors so may compromize the situation as well.

It is suggested that ” Citalopram (Celexa), escitalopram (Ciprolex), venlafaxine (Effexor), mirtazapine (Remeron), and reboxetine are weak or negligible inhibitors of CYP isozymes in vitro and are less likely than other second-generation antidepressants to interact with co-administered medications.”

from:

Clinical Therapeutics
Volume 30, Issue 7, July 2008, Pages 1206-1227
Clinically relevant pharmacokinetic drug interactions with second-generation antidepressants: An update
Edoardo Spina MD, a, , Vincenza Santoro BSca and Concetta D’Arrigo BSca
link

If you did not wish to use another anti-depressant, this would mean either stopping the offending anti-depressant, altering the dose of tamoxifen or going to an aromatase inhibitor – the latter which is only effective in post-menopausal cases…

aromatase inhibitors are not fun drugs because “aromatase inhibitors are not ideal for all women because they are associated with substantially more common and often more severe musculoskeletal complaints that often lead to nonadherence (35,36), as well as with higher long-term risks for osteoporosis and fractures” [from Hayes, 2008 above]
The good news I have now found, is only 7% of people are slow metabolizers; the bad news is finding out which ones is only a research item.
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