Genetic testing: "Personalized medicine," liver enzymes, genotypes, GeneSightRx, Genomind, etc.

[Nana401]

yes I am a poor metabolizer and it effects everything I take, not a happy camper

 

[ChessieCat]

28 minutes ago, freedomfrombondage said:

 

I switched to the liquid.  It was sort of funny actually.  All my friends told me to go to a doctor to ween down. I was like yea I have had zero success with that but sure, I'll take y'alls advice even though everything is going fine.

 

So I go to the doctor, he has me take a 300 dollar Genomind test and tells me that because of my genetics that I would do well on an SSRI and ADHD meds.  Keep in mind, I am a recovered drug addict and adderall/cocaine was my jam.  He told me I should go back up to 20 mg and go on Adderall EVEN THOUGH I HAD NO SYMPTOMS OF DEPRESSION, ANXIETY,  ETC, I literally just went to him to listen to friends and family.  I asked him if that test has a proven causation between genetic dispositions or if it was simply a correlation that people who had a certain mutation also had a disproportionately higher chance of developing a relative condition then the rest of the population.  He stared at me, told me it was a correlation to which I replied so you basically talked to me for fifteen minutes and made a decision based of a correlation that I should be on a higher dosage of lex and back on a drug (a drug whose script i used to snort the whole bottle of in a night mind you lol).  He just stared blankly again and said well it was just a suggestion.  I said no thank you, I don't want more drugs.  I'll take meditation, proper diet, exercise and liquid lexapro so i can continue to ween down.  He said okay, I'll write the script and that was that lol.

 

It was more expensive but totally worth it! 

 

[Altostrata]

!!!!!!! The definition of phoning it in, psychiatrist-style.

[DrugfreeProf]

From the illustrious (sarc) Psychiatric Times: 

I still hear from clients that their psychiatrists are using these tests to guide prescription practices--but there's no evidence that they are effective!

 https://www.psychiatrictimes.com/psychopharmacology/psychiatric-pharmacogenomic-testing-evidence-base

 

Current expert consensus on psychiatric pharmacogenomic panels

Expert consensus publications and editorials from thought leaders in psychiatry in the past 3 years have consistently concluded that psychiatric pharmacogenomic panels (AKA combinatorial pharmacogenetic tests) are not currently evidence based, and clinical decisions should not be based on their reports.^2-9 In fact, on October 31, 2018, the FDA published a safety communication warning against the use of many pharmacogenomic tests with the statement:

For example, the FDA is aware of genetic tests that claim results can be used to help physicians identify which antidepressant medication would have increased effectiveness or side effects compared to other antidepressant medications. However, the relationship between DNA variations and the effectiveness of antidepressant medication has never been established. The FDA is aware that health care providers may have made inappropriate changes to a patient's medication based on the results from genetic tests that claim to provide information on the personalized dosage or treatment regimens for some antidepressants. Patients and health care providers should not make changes to a patient's medication regimen based on the results from genetic tests that claim to predict a patient's response to specific medications, but are not supported by scientific or clinical evidence to support this use, because doing so may put the patient at risk for potentially serious health consequences.¹⁰

[Altostrata]

Moved to Media. This is not a scientific journal.

[ChessieCat]

UK sites.  Please note these are NOT recommendations, just sites I found when I did a search online.

 

https://www.nhs.uk/conditions/genetic-and-genomic-testing/

 

https://www.myogenes.com/

 

https://www.geneticdisordersuk.org/beginners-guide-to-genetics/genetic-testing/

 

https://geneticalliance.org.uk/information/service-and-testing/

[Altostrata]

Again, about Genomind and similar genetic tests:

 

These tests are very much hyped, to sell to doctors and patients to make a profit. They do not show what drugs will "work" for you. What they show is what some drugs might cause problems when metabolized in your liver.

 

Since drugs are also metabolized via other avenues, such as in the kidneys, these tests do not even address the entire universe of drugs.

 

What these tests show is that your liver may handle certain drugs certain ways. It does not show what psychiatric drugs would "work" -- presumably, that means manifesting the miracle of eliminating "depression" or whatever. They merely indicates which drugs are *less likely* to cause adverse effects via liver metabolism.

 

Those drugs still may cause adverse effects via other avenues, however, and they may not miraculously "work".

 

The genetic tests may help doctors choose the drugs less likely to make you sick from adverse effects. They are mostly useless in tapering and withdrawal.

[Erell]

On 12/21/2021 at 12:19 AM, Altostrata said:

The genetic tests may help doctors choose the drugs less likely to make you sick from adverse effects. They are mostly useless in tapering and withdrawal.

I agree: I don't see how it could be useful once the mess is done.

However, having decided last October to do a very long hold, I have a question: my prescriber seems to have discovered his "new toy" with these tests recently and insists on the importance of doing this test to every patients (not covered by insurance in my country!).

Switching to another molecule that a possible test would recommend is out of question for me, but he did scare me about a possible cumulative effect if I do a long hold: I shared with him that I had found a psychotherapist to work with from January on my fear of intrusive thoughts, and his answer was: “That's great, but if you are a poor metabolizer and if it's a side effect, it will keep on increasing anyway”.
(Just when I share that I need help, he finds nothing better to do than to reinforce my fear, great!)

Anyway, as I don't trust doctors anymore, I've done some research the last few days, but don't really understand what I read and what is exaclty our contemporary knowledge on this subject.
What about these tests in case of a long hold? Does this test mean that if a person is a slow metabolizer, the level of the drug in the blood just keeps increasing?

 

[Altostrata]

6 hours ago, Erell said:

my prescriber seems to have discovered his "new toy" with these tests recently and insists on the importance of doing this test to every patients (not covered by insurance in my country!).

 

If I were you, I'd refuse to pay for it. Gently but firmly, of course.

[Caesar65]

 

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Posted Friday at 01:41 AM

I like to express an important item I feel strongly engaged with and want to share it with you. I would like to find out, about the experience of others concerning this important point, which is bothering me a lot. 

 

I think that I am a so-called “ weak metabolizer “ and I think there are many cases of side-effects and withdrawal symptoms in context with it. This could be the reason why some people have only mild side effects/ withdrawal symptoms and the same of many others are worse, severe and long lasting. 
In my case, the regularly serum level control which shall be done already  before the prescription of an antidepressant was never done, and also not while I was taking it, and not, when I reported my worse side effects of Escitalopram. ( the same happened with Fluoxetin, Zoloft and all the others before the Lexapro Aera.) 

Whenever I didn’t feel less depressed, but side effects, the drug was just replaced by another one until Lexapro I got the prescription first in 2004 for 18 long years. 

In the German Guidelines it is very recommended, and in my case never ever done! And this is my explanation that I have become much more and stronger side effects over the years with Lexapro, and I was not aware of the reason given.

Perhaps I would not have been and would not be still in this unbearable situation as I am now, if the dose would have been moderate, instead of getting the prescription of the maximum dose of 20 mg. 😢The dose was changed several times, and remained until withdrawal for 20 mg. 

 

If serum levels are outside the therapeutic range, measures should be taken to correct this, e.g. Reassessing and promoting adherence;

Testing and discontinuation of interacting substances if necessary (levels too low, e.g., due to smoking, gingko, St. John's wort; levels too high, e.g., due to grapefruit diet);

Dose increase when levels are too low due to unalterable interactions or genetic predisposition (so-called "ultra-rapid metabolizers");

Dose reduction when the level is too high due to invariable interactions or genetic predisposition (so-called "poor metabolizer").

 

Among the cytochrome P450 (CYP) enzymes of the 2C family, through which about 20% of all drugs are metabolized, CYP2C19 plays the major role. Clinically relevant substrates include numerous antidepressants and neuroleptics, as well as clopidogrel and proton pump inhibitors. In this review, substrates, inhibitors, and inducers of the CYP2C19 isoenzyme are presented, the importance of genetic polymorphisms is addressed, and the clinical relevance of some interactions is described.

 

PS: Back to the weak metabolizer problem, I think about my mother, who had to take  Clopidogrel, because of her peripheral arterial occlusive disease.  And there were two stents in both legs and even though she took it, there always occured the same problems with the rapid reclosure again after a short time. And being a small metabolizer could have been the reason for this problem, the doctors said then. 

We went through horrible times, and mom was suffering for many years.

 

A possible reason for a lack of response to clopidogrel therapy ("clopidogrel resistance") could be the genetically determined variability of CYP2C19. In slow metabolizers, platelet reactivity may be preserved under clopidogrel therapy to the extent that stent thrombosis cannot be excluded after percutaneous coronary intervention (PCI). It has been shown in several studies that the presence of deficient CYP2C19 alleles in patients treated with clopidogrel is associated with an increased rate of cardiovascular events or stent thrombosis. For example, in the clopidogrel arm of the TRITON-TIMI-38 trial, the number of stent thromboses was increased threefold and mortality was increased by half when patients were carriers of a deficient CYP2C19 allele [9, 11].

 

[Altostrata]

"Weak metabolizer" refers to liver functioning, that's what "cyp" indicates. One can have a perfectly normal, healthy liver but not be able to metabolize certain drugs due to genetic makeup. This is not the fault of the liver but of the drug.

 

Inability to metabolize certain drugs is responsible for some, but not all, adverse drug reactions. Polypharmacy and increased drug burden demands more from liver metabolism and can also cause adverse drug reactions in people with normal, rapid, or even ultra-rapid liver metabolism.

 

In fact, one of the danger for people with rapid or ultra-rapid liver metabolism is they can handle excessive drug burdens for a long time, but eventually they experience liver damage from being overloaded.

 

On 3/25/2023 at 4:49 PM, Caesar65 said:

I think that I am a so-called “ weak metabolizer “ and I think there are many cases of side-effects and withdrawal symptoms in context with it. This could be the reason why some people have only mild side effects/ withdrawal symptoms and the same of many others are worse, severe and long lasting. 

 

Being a weak (aka slow) metabolizer may have caused adverse drug reactions while you were taking the drug, @Caesar65, but has no bearing on your development of withdrawal symptoms. Slower metabolism of the drug would mean your system has more time to re-adapt after drug cessation, so it could be viewed as a advantage in tapering.

 

You probably developed withdrawal symptoms from going off 20mg escitalopram over only 5 weeks, not because you might be a "poor" or slow metabolizer of escitalopram.

 

Quite often, people post psychopharmacological material here that they do not understand and think there might be a simple explanation for their problems in that material. Just about every aspect of this has been covered since this site was founded in 2011. Please see our other discussions about liver metabolism and cyp.

[Caesar65]

2 hours ago, Altostrata said:

You probably developed withdrawal symptoms from going off 20mg escitalopram over only 5 weeks, not because you might be a "poor" or slow metabolizer of escitalopram.

 

Quite often, people post psychopharmacological material here that they do not understand and think there might be a simple explanation for their problems in that material. Just about every aspect of this has been covered since this site was founded in 2011. Please see our other discussions about liver metabolism and cyp.

I understand and agree with you. 
But I didn’t consider that as being a simple explanation, but an explanation why I had stronger side effects developed when I was on the maximum dose of 20 mg, this is what I wanted to express. 
And I feel that it was not correct, from my doctor, that my serum level was never controlled, while I was on Lexapro. 
And of course the only and main reason why I am still having these unbearable symptoms is because withdrawal happened within only 5 weeks😢. The doctor told me, just to do so! And because of my severe stomach problems with heartburn at this time, I was glad to hear that. I was so naiv. 
And I also think, that an autonomic damage was caused through the longtime use of this drug. Dysautonomia?! Could this be the case?! There are many different and varied symptoms for this. 
What do you think? 

 

And there are still many doctors, like mine, who don’t pay much attention to the suffering caused through their wrong advice. 
In this new report of Mark Horowitz I read a lot about it. It it so frustrating. 

 

https://www.sciencedirect.com/science/article/pii/S0022395623001309

 

 

[Altostrata]

3 hours ago, Caesar65 said:

But I didn’t consider that as being a simple explanation, but an explanation why I had stronger side effects developed when I was on the maximum dose of 20 mg, this is what I wanted to express. 

 

We don't know. Could be your body just did not get along with the drug, or the dosage was too high for you.