tamoxifen and paxil

Of all of the SSRI's, Paxil and Prozac strongly inhibit the CYP2D6 substrate Tamoxifen's breakdown into it's metabolites. While not an SSRI, Wellbutron also inhibits this pathway strongly.



SSRI's which weakly inhibit CYP2D6 are Celexa and Lexapro. Lexapro is known to help panic.



One good alternative, imo, would be to work with a psychopharmacologist (an M.D., who specializes in drug chemistry and effects).



As Paxil is an SSRI, in general one can substitute another SSRI (slowing, with slow incremental steps up) and weaning of Paxil down concomitantly. Under a physician's direction, one may hopefully avoid the intense Serotonin withdraw for which Paxil is known, as you are substituting another serotonin agent.



Lastly, anti anxiety drugs are very effective in helping with anxiety. A replaced SSRI drug like Lexapro, in low dose added to by an anxiety fighting drug (like Ativan) is a commonly used combination for anxiety/depression surrounding breast cancer.



This might help you reach the best of all possible worlds: coverage for you ER+ cancer as you wish, as well as no abrupt weaning of Paxil with a slow move on up on an alternative, and coverage for panic.



I believe there are good alternatives for you, and wish you well on your journey.



Tender

I have good results with Valium for panic attacks, but I'm not sure if it's good for regular long term use.  I once used it for an entire year for panic attacks, but then the attacks stopped.  I recently began using it again for overwhelming anxiety and mild panic, but only on an as needed basis because it stops an attack pretty quick for me.

Good luck and I hope you find something that works for you on both fronts.

Cynthia 

I thought tamoxifen wasn't recommended for post-DCIS any more?  Though I haven't researched it carefully at all.....this (my question) is a very uninformed question. 

I need to correct my post of last night, so as to not provide misinformation. Thank you, fellow ladies, for re-focusing my brain, and I'm sorry for it's imprecise information.



Nada, since you are an not an "extensive metabolizer" via the CYP2D6 pathway, but rather an "intermediate" metabolizer, than avoidance of any inhibition of the CYP2D6 pathway, even by use of a weak inhibitor SSRI (Selective Serotonin Reuptake Inhibitor such as Celexa or Lexapro) is best, should you consider taking Tamoxifen. I'm sorry I commented elsewise; not a clear thinking moment.



The picture remains complicated, imo, then as to Effexor (venlafaxine) and Cymbalta. They are both SNRI's (serotonin norepinepherine reuptake inhibitors), and both are metabolized partially through the CYP2D6 pathway. They have not made their way to the famed Flockhart table which dear Susie brought to our attention eons ago (smile face).



Here is a brief summary of their breakdown:



Effexor (Venlafaxine) Metabolism and Excretion:



Following absorption, venlafaxine undergoes extensive presystemic metabolism in the liver,

primarily to ODV, but also to N-desmethylvenlafaxine, N,O-didesmethylvenlafaxine, and other

minor metabolites. In vitro studies indicate that the formation of ODV is catalyzed byCYP2D6;

this has been confirmed in a clinical study showing that patients with low CYP2D6 levels (“poor

metabolizers”) had increased levels of venlafaxine and reduced levels of ODV compared to

people with normal CYP2D6 (“extensive metabolizers”). http://www.effexorxr.com/?sk=4646 (prescribing information)



Cymbalta (Duloxetine)



Preclinical studies have shown that duloxetine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake and a less potent inhibitor of dopamine reuptake. Elimination of duloxetine is mainly through hepatic metabolism involving two P450 isozymes, CYP2D6 and CYP1A2. Both CYP2D6 and CYP1A2 catalyze the oxidation of the naphthyl ring in vitro.

http://pi.lilly.com/us/cymbalta-pi.pdf





As an "intermediate" metabolizer of CYP2D6, it appears using any of the SSRI's or SSNI's for anxiety/depression is questionable if one is considering Tamoxifen.



BuSpar® (buspirone hydrochloride tablets, USP) is an antianxiety agent that is not

chemically or pharmacologically related to the benzodiazepines, barbiturates, or other

sedative/anxiolytic drugs. It has been shown in vitro to be metabolized by CYP3A4, a differing pathway from CYP2D6.



Nada, you say your problem is mainly the horrible withdrawal effects from Paxil. Paxil, of all the SSRI's is known for significant withdrawal effects. As I said in my post above, substituting a different SSRI for Paxil, one with less withdrawal effects can be done. Then one can gradually taper from it too, hopefully without the severe side effects some notice from tapering from Paxil. These SSRI's are not all the same in their side effect and withdrawal profile amongst individual patients. All of this must be done under the watchful eye of a physician, but it is a possible solution to your problem of Paxil withdrawal.



It does not solve the Tamoxifen use while on an SSRI or SSNI, but then maybe weaning off these agents all together and utilizing a different anxiety drug would be a consideration which would then, in time, allow Tamoxifen's use.



Cynthia's point about ER+ DCIS is valid. Some physicians and patient's elect not to give a hormonal in this setting, especially if low grade, and other's may feel it is acceptable to cover for 5 years or so to minimize any recurrence or contralateral breast disease. It is all a risk/benefit analysis, and there's no easy answer.



Thank you to my friends here for their help. I hope this post, while to verbose, answers your question more clearly.



Tender

Edit update word just in from Saluki:" The plasma endoxifen concentration was slightly reduced in women taking venlafaxine, a weak inhibitor of CYP2D6, whereas the plasma endoxifen concentration was reduced substantially in subjects who took paroxetine (a potent inhibitor of CYP2D6)". JNCI Journal of the National Cancer Institute 2005 97(1):30-39; doi:10.1093/jnci/dji005 Thanks, Susie. It will be nice too, when the Flockhart table updates this useful information.T.

So if you are a poor metabolizer, you will get less of an effect from effexor? I ask because I was on it for a year at a low dose and it helped me a lot.

Thanks GALynne for the info.!

Amy,

Tamoxifen is still used for post menapausal women because it  does not  lessen bone density. I am post menopausal, and I'm on Tamoxifen.

Karoline 

Basha,

Glad you found a combination that works. 

Hope you can metabolize the Tamox and do not have to change.

Karoline