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precaryous
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Default Apr 19, 2019 at 11:52 AM
  #1
I have been tried on many antidepressants. Either they didn’t work or the side effects were intolerable.

Having looked at the newer antidepressants, many seem to be a reworking or combinations of older antidepressants. My psychologist is encouraging me to try again. But I feel therapy will end up with me arguing and complaining about the new drug....instead of therapy.

I’m very resistant to trying new antidepressants.

Has anyone taken the blood test, cytochrome P450 (CYP450) , and found it helped pinpoint a successful antidepressant regimen?
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Default Apr 19, 2019 at 05:34 PM
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Quote:
Originally Posted by precaryous View Post
I have been tried on many antidepressants. Either they didn’t work or the side effects were intolerable.


Having looked at the newer antidepressants, many seem to be a reworking or combinations of older antidepressants. My psychologist is encouraging me to try again. But I feel therapy will end up with me arguing and complaining about the new drug....instead of therapy.


I’m very resistant to trying new antidepressants.


Has anyone taken the blood test, cytochrome P450 (CYP450) , and found it helped pinpoint a successful antidepressant regimen?


I took the genesite test which covers a bunch of enzymes. For TRD it's mainly useful for convincing your new PDoc not to try lots of meds you've already failed on.
HTH
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Default May 10, 2019 at 09:56 AM
  #3
I did a SNP array (ancestryDNA, though 23andme would also work) and used that data. It looks at the same loci, it's just not regulated as a medical test and they don't guarantee as much accuracy and you kind of have to do some of the interpretation yourself matching your results to the relevant SNPs. A site/program called promethease helps.
The upside is it can be way cheaper if your insurance won't cover testing. It's usually like $100, $70 if they have a sale.

Later I actually did WGS too, but that's definitely overkill if you just want to know for meds.

If you want to know about CYP2D6, a pretty good indicator is whether or not codeine works for you. When I found out about this it suddenly made sense why codeine always seemed useless to me, I'm a CYP2D6 poor metabolizer meaning that my body doesn't turn codeine into morphine like most people.
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Default May 10, 2019 at 02:01 PM
  #4
Hi LabRat27~~I just posted a question re: a new drug that's FDA approved - 'resketamine.' Look at my post and see if that might help you...

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Default May 16, 2019 at 05:45 PM
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Quote:
Originally Posted by precaryous View Post
I have been tried on many antidepressants. Either they didn’t work or the side effects were intolerable.

Having looked at the newer antidepressants, many seem to be a reworking or combinations of older antidepressants. My psychologist is encouraging me to try again. But I feel therapy will end up with me arguing and complaining about the new drug....instead of therapy.

I’m very resistant to trying new antidepressants.

Has anyone taken the blood test, cytochrome P450 (CYP450) , and found it helped pinpoint a successful antidepressant regimen?


mine came back normal, and the genesight test *if you live in the USA* some people have found it beneficial, mine was useless. the drugs it said they were going to work for me didn't, and those that were not going to work, did (very few) so it varies. some people have found success with it. good luck
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Default May 16, 2019 at 07:09 PM
  #6
what is this test ? and when was it introduced ? after 10 years of taking anti depressants and whatever Seroquel is known to be. i'm literally sick and exhausted of everything. doctors and lawyers. nobody ever suggested a test of any kind ? or how about a brain scan to show how well the drugs are working ? NOPE ! DOH DEE DAA now i'm just a zombie waiting for a position to be on the new version of the walking dead. music is the only thing that makes me feel good only the effect does'nt last long. if they could only bottle it. i'll be waiting !
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Default May 16, 2019 at 09:51 PM
  #7
Okay, so genesight is just a brand. It is based on an analysis of your DNA.

What the test actually looks at are "SNPs." These are one letter in a specific gene (A, C, T, G). The SNPs they look at are ones that are different in different people, and identify which version of a gene (allele) you have. They can't say with absolute certainty, but it can check for most of the common variants.

Some of the genes it looks at are cytochrome P450 enzymes. There are a few others I can explain if anyone wants, but I'll keep this to the CYP genes to stay kind of on topic for the thread, and because this explanation is already long and complicated.

Cytochrome P450 enzymes are enzymes in the liver that help break down certain drugs. There are a lot of them, but some meds only get broken down by one or two specific ones.
There is also quite a bit of variation. Some of the enzymes have little to no variation within a population - almost everyone has 2 functional copies. But some, like CYP2D6 (the most common example) show much more variation, with non-functional, less-functional, normal, and extra strong versions all existing and not being super uncommon.
CYP2D6 is also involved in metabolizing a lot of meds, including psych drugs, and is one of the most important ones looked at in tests.

Without getting too much into the chemistry, some meds stop working when they get broken down, some meds have different outcomes depending on how they're broken down, and a few meds only work if they get broken down by these enzymes (e.g. codeine doesn't work for people without functional CYP2D6 because that's the enzyme that turns it into morphine!).

We all have 2 alleles for every gene (except some X chromosome stuff, but that's a weird exception). For a lot of genes, as long as one is functional it will be the same as 2 being functional. But if both of your copies are "broken" versions, then you won't have a functional copy of that enzyme to perform the function.
This matters for psych meds because of the reasons above, whether or not and how they get broken down affects levels of the med and the stuff it gets broken down into.
Meds can also affect the efficiency of the enzymes. Some meds will impair or block the function of certain enzymes. So like Prozac inhibits CYP2D6. If someone was taking codeine and started taking Prozac, the codeine would become less effective because Prozac is inhibiting CYP2D6.
This can lead to all kinds of fun med interactions. A lot of these interactions result in higher levels of the meds in your body, so if I'm on, say, Abilify, and then start taking Prozac, the Prozac can increase the levels of Abilify in my system, and I could start having new or stronger Abilify side effects because I started Prozac.
I might attribute them to the Prozac if I didn't know though. This is why they say not to have grapefruit if you're on certain meds, because it inhibits CYP3A4.

So, you can imagine that variation in how you break down meds and what they're broken down into--some of which have their own effects and are called "active metabolites" and can have different effects than the original meds or other products--will affect which meds might work for you.
I prefer to avoid drugs that are primarily metabolized through CYP2D6 because I have two non functional copies.

But even some SNPs are inconclusive. The test is looking at single nucleotides, so sometimes a certain variation is always or almost always found in people with a nonfunctional copy, but others tend to be found in nonfunctional copies, or mean that you have a less common variation which may or may not be functional.

Whether or not it's a functional version can be determined with sequencing, including gene sequencing, whole exome sequencing, or whole genome sequencing. I got my whole genome sequenced for $500, but unlike Genesight I had to do the data analysis and interpretation myself, and it wasn't covered by insurance. Honestly it's excessive if this is the only thing you want to check, I did it because I wanted to.

So these tests can tell you based on some of these genes that certain meds are more or less likely to work well for you, but it's just one of many factors that goes into whether or not a med will work for you. There are so many more factors we don't understand, it just helps make educated guesses when you're deciding what to try first.

Genesight also looks at SNPs in a few other genes that affect how your brain reacts to meds. Often we're not sure why exactly, but studies will show that, on average, a certain med is much more likely to work in people with a certain SNP. There are a ton of possible explanations, both direct and indirect, but it can at least be used to make better guesses about what med is more or less likely to work.

Genesight or any other genetic test absolutely cannot tell you that any specific med will or won't work for you.
And if you are interested in the most basic analysis, a $100 test (or $60 on sale) from 23andme or AncestryDNA will include most of these SNPs. They're not FDA approved for medical use and don't have that guaranteed level of accuracy, but they are good enough for educated guesses.
I did that before I did whole genome sequencing, and I used a program called promethease that generates a convenient report from your raw data that lists your SNPs including the most relevant ones and does give you some pharmacology interpretation, though you'd want to check with your doc about that interpretation.

Genesight really does help make better guesses about which med to try first. An analysis that looked at different studies showed that
Quote:
"Patients who received the GeneSight test to guide psychotropic medication selection had improved response to depression treatment, greater improvements in measures of depression, and greater patient and clinician satisfaction compared with patients who received treatment as usual."
source


The individual studies didn't really have enough data to draw any conclusions, especially about "effect size," but at a glance it seems like the rate of response to the meds based on genesight or not based on genesight, depending on how they measured it and a million other disclaimers and limitations, was about 1.5-2x higher (table six)

This ended up a lot longer than expected. Full disclaimers: not a doctor, not a pharmacist, no extensive training in pharmacology. Basically not qualified wrt human health outcomes, though I have quite a bit of familiarity, and none of this should be taken as health advice without talking to your doc.
(I am a biologist, and I do know about genetics and it's kind of part of what I do for a living, so I would certainly hope I know what I'm talking about there)
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Default May 17, 2019 at 11:46 AM
  #8
Quote:
Originally Posted by LabRat27 View Post
Okay, so genesight is just a brand. It is based on an analysis of your DNA.

What the test actually looks at are "SNPs." These are one letter in a specific gene (A, C, T, G). The SNPs they look at are ones that are different in different people, and identify which version of a gene (allele) you have. They can't say with absolute certainty, but it can check for most of the common variants.

Some of the genes it looks at are cytochrome P450 enzymes. There are a few others I can explain if anyone wants, but I'll keep this to the CYP genes to stay kind of on topic for the thread, and because this explanation is already long and complicated.

Cytochrome P450 enzymes are enzymes in the liver that help break down certain drugs. There are a lot of them, but some meds only get broken down by one or two specific ones.
There is also quite a bit of variation. Some of the enzymes have little to no variation within a population - almost everyone has 2 functional copies. But some, like CYP2D6 (the most common example) show much more variation, with non-functional, less-functional, normal, and extra strong versions all existing and not being super uncommon.
CYP2D6 is also involved in metabolizing a lot of meds, including psych drugs, and is one of the most important ones looked at in tests.

Without getting too much into the chemistry, some meds stop working when they get broken down, some meds have different outcomes depending on how they're broken down, and a few meds only work if they get broken down by these enzymes (e.g. codeine doesn't work for people without functional CYP2D6 because that's the enzyme that turns it into morphine!).

We all have 2 alleles for every gene (except some X chromosome stuff, but that's a weird exception). For a lot of genes, as long as one is functional it will be the same as 2 being functional. But if both of your copies are "broken" versions, then you won't have a functional copy of that enzyme to perform the function.
This matters for psych meds because of the reasons above, whether or not and how they get broken down affects levels of the med and the stuff it gets broken down into.
Meds can also affect the efficiency of the enzymes. Some meds will impair or block the function of certain enzymes. So like Prozac inhibits CYP2D6. If someone was taking codeine and started taking Prozac, the codeine would become less effective because Prozac is inhibiting CYP2D6.
This can lead to all kinds of fun med interactions. A lot of these interactions result in higher levels of the meds in your body, so if I'm on, say, Abilify, and then start taking Prozac, the Prozac can increase the levels of Abilify in my system, and I could start having new or stronger Abilify side effects because I started Prozac.
I might attribute them to the Prozac if I didn't know though. This is why they say not to have grapefruit if you're on certain meds, because it inhibits CYP3A4.

So, you can imagine that variation in how you break down meds and what they're broken down into--some of which have their own effects and are called "active metabolites" and can have different effects than the original meds or other products--will affect which meds might work for you.
I prefer to avoid drugs that are primarily metabolized through CYP2D6 because I have two non functional copies.

But even some SNPs are inconclusive. The test is looking at single nucleotides, so sometimes a certain variation is always or almost always found in people with a nonfunctional copy, but others tend to be found in nonfunctional copies, or mean that you have a less common variation which may or may not be functional.

Whether or not it's a functional version can be determined with sequencing, including gene sequencing, whole exome sequencing, or whole genome sequencing. I got my whole genome sequenced for $500, but unlike Genesight I had to do the data analysis and interpretation myself, and it wasn't covered by insurance. Honestly it's excessive if this is the only thing you want to check, I did it because I wanted to.

So these tests can tell you based on some of these genes that certain meds are more or less likely to work well for you, but it's just one of many factors that goes into whether or not a med will work for you. There are so many more factors we don't understand, it just helps make educated guesses when you're deciding what to try first.

Genesight also looks at SNPs in a few other genes that affect how your brain reacts to meds. Often we're not sure why exactly, but studies will show that, on average, a certain med is much more likely to work in people with a certain SNP. There are a ton of possible explanations, both direct and indirect, but it can at least be used to make better guesses about what med is more or less likely to work.

Genesight or any other genetic test absolutely cannot tell you that any specific med will or won't work for you.
And if you are interested in the most basic analysis, a $100 test (or $60 on sale) from 23andme or AncestryDNA will include most of these SNPs. They're not FDA approved for medical use and don't have that guaranteed level of accuracy, but they are good enough for educated guesses.
I did that before I did whole genome sequencing, and I used a program called promethease that generates a convenient report from your raw data that lists your SNPs including the most relevant ones and does give you some pharmacology interpretation, though you'd want to check with your doc about that interpretation.

Genesight really does help make better guesses about which med to try first. An analysis that looked at different studies showed that

source


The individual studies didn't really have enough data to draw any conclusions, especially about "effect size," but at a glance it seems like the rate of response to the meds based on genesight or not based on genesight, depending on how they measured it and a million other disclaimers and limitations, was about 1.5-2x higher (table six)

This ended up a lot longer than expected. Full disclaimers: not a doctor, not a pharmacist, no extensive training in pharmacology. Basically not qualified wrt human health outcomes, though I have quite a bit of familiarity, and none of this should be taken as health advice without talking to your doc.
(I am a biologist, and I do know about genetics and it's kind of part of what I do for a living, so I would certainly hope I know what I'm talking about there)
thanks for the 411. does'nt do me any good now though. and you took this test ? how much ? why is'nt this requied for all before they start peddling their drugs on people ? i guess i was a guinea pig ? is that moral ? is that ethical ? thanks though
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