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beneficii
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25 Jan 2017, 10:06 am

I've been put on Prozac twice and both times I had some improvement followed by worsening of my conditions. Now a few years ago, we considered a bipolar diagnosis, but since then I've been moved back to a depression diagnosis, and have had good results with other antidepressants.

I've recently had my whole genome sequenced, and I found out the reason why Prozac was ineffective. I am homozygous for a non-functioning variant of the gene that codes the CYP2D6 enzyme (it's the CYP2D6*4 variant), and that enzyme is required to convert Prozac to its only active metabolite norfluoxetine. Since that necessary conversion could not occur due to not producing the necessary enzyme, Prozac had no effect, and the brief improvement after starting Prozac was likely due to a placebo effect.

I told my psychiatrist about it and he agreed, and he noted that fact.

The CYP2D6*4 variant is not uncommon, and occurs in 25% of white people:

http://emedicine.medscape.com/article/1879354-overview

So I think if you've had the "Prozac poop-out", you should consider it may be occurring because you lack the enzyme to use it correctly and any initial improvement was because of a placebo effect.


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beneficii
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25 Jan 2017, 12:30 pm

Looking more closely at the report, I'm actually homozygous for 2 variants of the CYP2D6, the aforementioned non-functioning variant CYP2D6*4 (rs3892097) AND the reduced-functioning variant CYP2D6*10 (rs1065852).

Here are the pages for each one:

https://www.ncbi.nlm.nih.gov/clinvar/RCV000018385.23/

https://www.ncbi.nlm.nih.gov/clinvar/RCV000018389.23/

And here are the population frequencies:

https://www.ncbi.nlm.nih.gov/variation/ ... |rs3892097

https://www.ncbi.nlm.nih.gov/variation/ ... |rs1065852

There are some variations across different groups. About 22% of white people here have CYP2D6*4 and about 24% of them have CYP2D6*10 (though as always most of the time someone has only one copy). CYP2D6*4 is virtually non-existent in East Asians, but CYP2D6*10 is quite common in East Asians, especially in Chinese and Vietnamese, with at least one copy occurring in more than half (but don't forget 24% of whites also have at least one copy of this variant).

So apparently I've had a double hit in this regard. Next time I see my psychiatrist, I'll update him (and actually hand him a copy of the report this time).


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firemonkey
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26 Jan 2017, 8:53 am

Have never been on Prozac but according to Promethease.



rs1065852(C;T)
Magnitude: 2
Repute:Bad
References:8
Carrier of one CYP2D6 decreased or non-functioning variant. Your body may have a reduced ability to process some medicines. You are a carrier for rs1065852(T;T)
(hide)
The wild type (normal) allele at this SNP is (C). The (T) variant indicates the presence of a non-wild type CYP2D6 variant, but it appears in many different variants so it can not be used to determine the presence of any particular variant. The most common variants it appears in are CYP2D6*10 and CYP2D6*4, but these are not the only ones.