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Bupropion (Wellbutrin) Interactions with Tamoxifen (Nolvadex)

@unreal24278 this is mainly a question for you because it seems like you get a kick out of this kind of thing but anyone else that can add any info would be much appreciated.

So I started taking Tamoxifen after reading the “ask physiolojik” thread. I was doing some random reading and noticed that bupropion supposedly has a major drug interaction with tamoxifen (as well as many SSRIs though bupropion is not an SSRI). It seems to do with bupropion reducing the activity of CYP2D6 which is responsible for breaking down the tamoxifen.

I know you are busy but when you get a chance could you take a look at this and see if you agree with the findings? I’m trying to determine if I need to try and come off bupropion. Of course the easy answer is yes but it’s going to be a major b-word that I’d rather not go through if I don’t have to.

I’m taking:
Bupropion 300 xl - 5+ yrs
Tamoxifen 20mg - 3 weeks

Thank you!


Looks like a problem.

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Tamoxifen is what one would consider a pro-drug, in it’s unmetabolised form/ unchanged form tamoxifen actually has very little affinity to the ER, it’s metabolites (afimoxifene) for instance have a much higher affinity for the ER and thus exert the actions regarding binding to sites containing ER and competitively block the effects of oestrogen’s.

One of the enzymes heavily responsible for metabolisation of tamoxifen is CYP2D6. Wellbutrin inhibits cyp2d6, thus the rate at which tamoxifen is metabolised may be too slow/innefficient for one to get proper benefit from tamoxifen when on drugs that interfere with 2d6 metabolism.

As an individual, I myself am an ultra rapid 2d6 metaboliser and thus for a drug like tamoxifen, a lower dose would actually serve me better (however depending on how the drug is excreted I may require a higher dose, fluoxetine for instance I require very high doses for therapeutic benefit). I can’t take codeine, aside from billiary spasm (incredibly unpleasant experience), I convert a very high percentage to morphine, thus codeine is actually rather dangerous for me.

Whether or not you have to come off the Wellbutrin, uncertain, you’d still likely get some form of therapeutic benefit from tamoxifen, you may have to take more (I’m no doctor, don’t take my advice as medical advice). If the Wellbutrin is significantly helping you with regard to mental health and stability, I’d stay on, it’s a risk/benefit assessment.

Do you NEED tamoxifen on TRT? Is it not possible for you to simply lower TRT/AAS dose?

Ye, I am fairly busy at the moment, I have some exams coming up, studying quite a bit. I’ve recently made some good friends (for first time in ages) thus I am frequently out and about,.


My main reason for using tamoxifen is I am prone to gyno. Even after having surgery to remove the glands 10+ yrs ago it started returning (before trt).

The bupropion never really made any big difference for me except give me a super stimulant type feeling for the first few months but besides that I never felt any better. It’s just one of those things that I kept taking because it didn’t make me feel worse and then life happens and you don’t really think about it. That is until something you would prefer to take is rendered useless by it.

Thank you for the response! I’m going to start the process of coming off of it.