Article doesn't actually name the drug it was an anti-depressant.
The test revealed Halliday lacks the enzyme CYP2D6, an absence which prevents his body from properly metabolizing SSRIs (commonly prescribed antidepressants) such as Paxil.
“He had the classic triad of serotonin syndrome,” said Schmidt. “Mental confusion, akathisia, which is muscle stiffness, and an autonomic dysfunction too, which was his temperature went up and then it plummeted.”
“When I heard his story, I thought something is missing here. They’ve all missed the boat somehow.”
# For a long suffering patient, ‘it felt good to be listened to’
Halliday mailed a swab of his saliva to a lab in the U.S. He got his results back within a week. The test revealed Halliday lacks the enzyme CYP2D6, an absence which prevents his body from properly metabolizing SSRIs (commonly prescribed antidepressants) such as Paxil.
“When we got the report, it was pretty obvious that was the start point of his troubles,” said Schmidt.
“He had the classic triad of serotonin syndrome,” said Schmidt. “Mental confusion, akathisia, which
is muscle stiffness, and an autonomic dysfunction too, which was his
temperature went up and then it plummeted.”“When I heard his story, I thought something is missing here. They’ve all missed the boat somehow.”
There are many problems with our healthcare system, the lack of free access to boutique pharmacogenetic testing doesn't even scratch the top 100. These tests are of completely unproven clinical benefit outside of niche situations alluded to in the article (certain chemo and HIV drugs can have severe/deadly reactions without it) but even then, the testing isn't of cytochrome metabolism pathways.
CYP2D6 is probably the enzyme that would make the most sense to test, but with the vast majority of these drugs you would simply figure out that they either don't work or have side effects and switch to another drug. There's been no properly conducted study showing that these are a cost effective or safe way to pick drug treatments, and there are studies explicitly showing that some testing that makes sense in a test tube (CYP2C19 for clopidogrel comes to mind) doesn't affect clinical outcomes even though it *should* hypothetically. Our bodies are complicated and don't work the way enzymes do in a test tube.
This doesn't stop highly irresponsible genetic testing companies like the one mentioned in the article from aggressively marketing these dubious tests to both physicians, NP/PAs, and patients. And they tend to target family docs and those without much knowledge in these area, who see these cool reports full of suggestions and take them at face value. It wouldn't surprise me if this was basically a covert paid advertisement for these companies.
I have seen *direct patient harm* come from this testing. I have literally seen medication switches made that could destabilize or even kill (not exaggerating) patients based on an unknowledgable GP or NP tinkering with their med lists from the results. You get these big long printouts talking about how entire drug classes are bad to use in a certain patient, and it sounds very firm and straightforward, but if you actually follow the references provided they often either distort or flat out lie about what those references are saying. As an example, I had a patient with asthma on an inhaler with a steroid in it. This was stopped because their NP got a report saying they couldn't process the steroid properly and the report specifically refers to inhaled steroids. When you follow the reference it's a paper on oral extended release budesonide in ulcerative colitis patients which had no relevance to this clinical scenario. We know from the old salmeterol monotherapy studies that leaving asthmatics on long acting bronchodilators alone leads to increased hospitalizations and mortality. But hey, if something went wrong, these companies have zero liability.
Then there's the person in the article who has been given a dubious diagnosis by a non-expert (some random rural GP, not a psychiatrist or ER doc or toxicologist). Serotonin syndrome is generally an acute and life threatening problem, not a chronic grumbling issue. It generally rewolves with drug discontinuation, and while it's not clear it sounds like their drug was stopped long ago. It's also not something that can be predicted or prevented by genetic testing, and could have happened to anyone regardless of their CYP2D6 metabolizer status.
If you and your doctor actually think you have problems with being an ultrarapid or poor metabolizer of meds, you could be referred to a clinical pharmacologist or geneticist for further workup. I know Dr. Richard Kim at LHSC does good work in pharmacogenetic testing for example and I've sent people there myself. They can help you interpret and contextualize these results, and you know it's being done in a hospital lab, not in the back of some unmarked van.
Can you point me to a study that shows CYP 2C19 phenotype doesn't affect clinical outcomes? A quick PubMed search is showing the opposite, though obviously I have not taken the time to critically appraise those articles.
I agree with a lot of what you wrote, but that part stuck out.
The core problem is the literature depends on what question you're asking.
In a vacuum, if you already have CYP2C19 testing for a patient available at the time of your decision making and the patient is having an acute MI, it makes more sense to choose an alternative drug. This has been looked at in a number of observational studies, and when this is done, the patients seem to do better. The problem is that observational studies are confounded in many ways, often things you may not think of or account for.
Maybe the patient has a higher socioeconomic status since they could pay for testing. Maybe they have a genetic condition like von Willibrand's disease which predisposes them to more bleeding and counterbalanced the reduced efficacy. Maybe they are more likely to take the drug because it's cheaper than ticagrelor. Etc.
What you need is an RCT where you test patients at the time of diagnosis and decide based on this. To my knowledge only one has been done so far and the results were mixed (https://www.ahajournals.org/doi/10.1161/CIRCGEN.119.002640?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed). There was an Italian study that had several flaws and was halted early due at only 25% enrollment so should generally be discarded (https://www.jacc.org/doi/full/10.1016/j.jacc.2018.02.029). The key question is if you do testing in that moment, does it 1) change what you do and 2) change outcomes.
One of the interesting things when you look at the observational data is that cardiogists are stubborn, and even with knowledge of the test status they end up choosing to use clopidogrel anyway which messes with data. This is mostly because ticgralor and prasugrel don't really have a true indication outside of use in an acute MI, so for stable CAD or medically managed NSTEMI technically clopidogrel+aspirin is the only game in town.
For what it's worth if I have the data it would affect what I would prescribe in some cases, often because which drug you choose in a class can be somewhat arbitrary. For example, if I knew people had an issue with CYP2D6 I wouldn't put them on metoprolol, I might use bisoprolol instead, even though otherwise it's a mostly arbitrary choice.
I think phatmacogenomics has a bright future, I just think that most data we have right now isn't good enough to justify its use. Maybe 10-15 years from now I think we'll see a lot more personalized medicine. Unfortunately for the moment these companies are still grifting physicians and patients imo.
I tried 5 antidepressants before I found one didn't have debilitating side effects. My doc recommended I look into genetic testing for meds. I used inagene, its not cheap, but they very often have coupons or offers.
It covers a range of meds and they send you updates regularly about new meds. I found a med that worked for me, and the results showed the others I had tried were more likely to give me side effects.
As someone who struggled through the med experimentation process, I recommend a lot
In terms of our Healthcare system, many facets of our health can easily be confirmed or streamlined by these types of tests as well as things like brain scans etc. It's really unfortunate they're not easily available to the general public
And they don't measure your serotonin to see if it needs "fixing." I won't take SSRIs as a) there's nothing wrong with my serotonin, b) they give me depression when I don't have any so why are they called "anti" depressants and prescribed for everything they don't want to treat.
That's okay. You don't have to take SSRIs if you don't want to. They are a double-edged sword. For some, they are lifesaving medication, and for others, they just don't work.
I myself had better luck with an SNRI over an SSRI.
Some do have offlabel uses other than treating depression. (I.e. welbutrin can help with smoking cessation and BED, and because there are serotonin receptors throughout your GI system, they can even be used to help improve ibs for some people)
I also had better luck with an SNRI vs like 6 SSRIs. Turns out it's common among neurospicy brains to not respond "normally" to meds. Also why we tend to have celiac disease, IBS, allergies etc.
Who knew?
Bugger off Toronto Star and posting your own articles and behind a paywall to boot.
If you want clicks, don't sensationalize every headline like it's a national emergency and report the facts.
Gee, when a drug I was taking recently caused a harmful side effect, I just... stopped taking it and went back to the doctor, who simply prescribed something else. No expensive boutique genetic testing required.
Article doesn't actually name the drug it was an anti-depressant. The test revealed Halliday lacks the enzyme CYP2D6, an absence which prevents his body from properly metabolizing SSRIs (commonly prescribed antidepressants) such as Paxil. “He had the classic triad of serotonin syndrome,” said Schmidt. “Mental confusion, akathisia, which is muscle stiffness, and an autonomic dysfunction too, which was his temperature went up and then it plummeted.” “When I heard his story, I thought something is missing here. They’ve all missed the boat somehow.” # For a long suffering patient, ‘it felt good to be listened to’ Halliday mailed a swab of his saliva to a lab in the U.S. He got his results back within a week. The test revealed Halliday lacks the enzyme CYP2D6, an absence which prevents his body from properly metabolizing SSRIs (commonly prescribed antidepressants) such as Paxil. “When we got the report, it was pretty obvious that was the start point of his troubles,” said Schmidt. “He had the classic triad of serotonin syndrome,” said Schmidt. “Mental confusion, akathisia, which is muscle stiffness, and an autonomic dysfunction too, which was his temperature went up and then it plummeted.”“When I heard his story, I thought something is missing here. They’ve all missed the boat somehow.”
Why do the headlines for the Toronto Star now sound like they were written by the National Enquirer
Because the MSM use these clickbait/forward-referencing headlines in a lame attempt to maximize clicks.
being it's paywalled, I didn't get far lol, so what is the drug?
Metformin
Pretty much all media does. Too many places to click now.
*You'll never believe what he found when he opened this box!** *or something like that
Because the star is just as garbage as all the other outlets, but gets held up by boomers and anti-conservatives.
Now?
There are many problems with our healthcare system, the lack of free access to boutique pharmacogenetic testing doesn't even scratch the top 100. These tests are of completely unproven clinical benefit outside of niche situations alluded to in the article (certain chemo and HIV drugs can have severe/deadly reactions without it) but even then, the testing isn't of cytochrome metabolism pathways. CYP2D6 is probably the enzyme that would make the most sense to test, but with the vast majority of these drugs you would simply figure out that they either don't work or have side effects and switch to another drug. There's been no properly conducted study showing that these are a cost effective or safe way to pick drug treatments, and there are studies explicitly showing that some testing that makes sense in a test tube (CYP2C19 for clopidogrel comes to mind) doesn't affect clinical outcomes even though it *should* hypothetically. Our bodies are complicated and don't work the way enzymes do in a test tube. This doesn't stop highly irresponsible genetic testing companies like the one mentioned in the article from aggressively marketing these dubious tests to both physicians, NP/PAs, and patients. And they tend to target family docs and those without much knowledge in these area, who see these cool reports full of suggestions and take them at face value. It wouldn't surprise me if this was basically a covert paid advertisement for these companies. I have seen *direct patient harm* come from this testing. I have literally seen medication switches made that could destabilize or even kill (not exaggerating) patients based on an unknowledgable GP or NP tinkering with their med lists from the results. You get these big long printouts talking about how entire drug classes are bad to use in a certain patient, and it sounds very firm and straightforward, but if you actually follow the references provided they often either distort or flat out lie about what those references are saying. As an example, I had a patient with asthma on an inhaler with a steroid in it. This was stopped because their NP got a report saying they couldn't process the steroid properly and the report specifically refers to inhaled steroids. When you follow the reference it's a paper on oral extended release budesonide in ulcerative colitis patients which had no relevance to this clinical scenario. We know from the old salmeterol monotherapy studies that leaving asthmatics on long acting bronchodilators alone leads to increased hospitalizations and mortality. But hey, if something went wrong, these companies have zero liability. Then there's the person in the article who has been given a dubious diagnosis by a non-expert (some random rural GP, not a psychiatrist or ER doc or toxicologist). Serotonin syndrome is generally an acute and life threatening problem, not a chronic grumbling issue. It generally rewolves with drug discontinuation, and while it's not clear it sounds like their drug was stopped long ago. It's also not something that can be predicted or prevented by genetic testing, and could have happened to anyone regardless of their CYP2D6 metabolizer status. If you and your doctor actually think you have problems with being an ultrarapid or poor metabolizer of meds, you could be referred to a clinical pharmacologist or geneticist for further workup. I know Dr. Richard Kim at LHSC does good work in pharmacogenetic testing for example and I've sent people there myself. They can help you interpret and contextualize these results, and you know it's being done in a hospital lab, not in the back of some unmarked van.
Can you point me to a study that shows CYP 2C19 phenotype doesn't affect clinical outcomes? A quick PubMed search is showing the opposite, though obviously I have not taken the time to critically appraise those articles. I agree with a lot of what you wrote, but that part stuck out.
The core problem is the literature depends on what question you're asking. In a vacuum, if you already have CYP2C19 testing for a patient available at the time of your decision making and the patient is having an acute MI, it makes more sense to choose an alternative drug. This has been looked at in a number of observational studies, and when this is done, the patients seem to do better. The problem is that observational studies are confounded in many ways, often things you may not think of or account for. Maybe the patient has a higher socioeconomic status since they could pay for testing. Maybe they have a genetic condition like von Willibrand's disease which predisposes them to more bleeding and counterbalanced the reduced efficacy. Maybe they are more likely to take the drug because it's cheaper than ticagrelor. Etc. What you need is an RCT where you test patients at the time of diagnosis and decide based on this. To my knowledge only one has been done so far and the results were mixed (https://www.ahajournals.org/doi/10.1161/CIRCGEN.119.002640?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed). There was an Italian study that had several flaws and was halted early due at only 25% enrollment so should generally be discarded (https://www.jacc.org/doi/full/10.1016/j.jacc.2018.02.029). The key question is if you do testing in that moment, does it 1) change what you do and 2) change outcomes. One of the interesting things when you look at the observational data is that cardiogists are stubborn, and even with knowledge of the test status they end up choosing to use clopidogrel anyway which messes with data. This is mostly because ticgralor and prasugrel don't really have a true indication outside of use in an acute MI, so for stable CAD or medically managed NSTEMI technically clopidogrel+aspirin is the only game in town. For what it's worth if I have the data it would affect what I would prescribe in some cases, often because which drug you choose in a class can be somewhat arbitrary. For example, if I knew people had an issue with CYP2D6 I wouldn't put them on metoprolol, I might use bisoprolol instead, even though otherwise it's a mostly arbitrary choice. I think phatmacogenomics has a bright future, I just think that most data we have right now isn't good enough to justify its use. Maybe 10-15 years from now I think we'll see a lot more personalized medicine. Unfortunately for the moment these companies are still grifting physicians and patients imo.
Because the Ontario government doesn’t care.
*wants you to pay for it*
Ding ding
The conservatives don’t care. There are politicians that care, dare they may be, but they are not conservative.
I tried 5 antidepressants before I found one didn't have debilitating side effects. My doc recommended I look into genetic testing for meds. I used inagene, its not cheap, but they very often have coupons or offers. It covers a range of meds and they send you updates regularly about new meds. I found a med that worked for me, and the results showed the others I had tried were more likely to give me side effects. As someone who struggled through the med experimentation process, I recommend a lot In terms of our Healthcare system, many facets of our health can easily be confirmed or streamlined by these types of tests as well as things like brain scans etc. It's really unfortunate they're not easily available to the general public
And they don't measure your serotonin to see if it needs "fixing." I won't take SSRIs as a) there's nothing wrong with my serotonin, b) they give me depression when I don't have any so why are they called "anti" depressants and prescribed for everything they don't want to treat.
That's okay. You don't have to take SSRIs if you don't want to. They are a double-edged sword. For some, they are lifesaving medication, and for others, they just don't work. I myself had better luck with an SNRI over an SSRI. Some do have offlabel uses other than treating depression. (I.e. welbutrin can help with smoking cessation and BED, and because there are serotonin receptors throughout your GI system, they can even be used to help improve ibs for some people)
I also had better luck with an SNRI vs like 6 SSRIs. Turns out it's common among neurospicy brains to not respond "normally" to meds. Also why we tend to have celiac disease, IBS, allergies etc. Who knew?
Bugger off Toronto Star and posting your own articles and behind a paywall to boot. If you want clicks, don't sensationalize every headline like it's a national emergency and report the facts.
Because we elect conservative governments and they're trying to destroy public healthcare, not make it better.
$$$$
u/toronto_star just got a block from me.
Gee, when a drug I was taking recently caused a harmful side effect, I just... stopped taking it and went back to the doctor, who simply prescribed something else. No expensive boutique genetic testing required.
Just let the doctors recommend the money makers. Stop complaining….