Pharmacogenetics personalised medicine: new frontier or nonsense?
Apparently my private health insurance covers pharmacogenetics testing to find the best ADHD medication. What is it, is it legit? What's the company going to do with my cheek swabs? How do doctors feel about me going up to them and say hey internet pharma bro tells me I should be taking this instead of what your years of medical school thinks.
What I can't figure out is how my insurance company benefits from this. I'm not paying extra for this service so I must be the product right? Here's part of the marketing FAQ info from my insurance provider:
Personalized Medicine uses advanced pharmacogenetic testing and pharmacist assistance to find the most effective medication for you.
If you’re starting a new medication for a mental health condition (such as anxiety or depression), chronic pain, attention deficit hyperactivity disorder (ADHD), or neurological conditions – or taking a medication for one of these conditions and it’s not working or causing side effects – Personalized Medicine could help. It’s offered through your extended health care benefits plan, so the cost of the test may be covered. To see the list of drugs tested, click here.
It involves a pharmacogenetic test. This is a type of test that identifies how you may respond to medications. Your test results are only for you and anyone you give consent to share them with, such as your doctor. The test is run by Personalized Prescribing Inc., a Canadian company. Manulife
(Forgot to mention this is for a Canadian employment extended health insurance.)
Genetic testing for predicting response to various pharmaceutical interventions is mostly about gene variants that impact drug metabolism, not necessarily drug response or likelihood of all serious side effects (e.g. drug allergies).
There's evidence that up to 80% of the population carries gene variants that impact drug metabolism, either slowing or accelerating breakdown and elimination of specific kinds of chemicals. Knowing which families of chemicals can result in potential under- or over-dosing is important, but it doesn't necessarily tell you which of the tolerable drugs will be most effective for your particular condition.
There's mixed evidence on whether pharmacogenomics actually helps people with various mental health conditions recover faster or better. The best evidence is that it does help achieve faster improvement in major depressive disorder. This could be because there are so many antidepressants with different mechanisms of action, and skipping trials of the ones with unfavorable metabolic profiles would save a great deal of time. [Personal experience, I've been prescribed most of them at one time or another, with varying results from totally ineffective to debilitating to emergency room visits. I would have a different life if the right one was found on the first or second try.]
For ADHD, the review I referenced didn't seem to show a substantial improvement from pharmacogenomic testing across multiple studies. The available mechanisms of action rely on a handful of drugs that are chemically similar to each other, so there's less scope for eliminating whole drug families that you might respond to unfavorably.
As far as how the insurance company benefits, fewer ineffective or harmful drug trials means fewer doctor visits. Earlier improvement generally means better long-term medical outcomes, especially for bipolar disorder and schizophrenia, where delayed treatment increases the likelihood of recurrent hospitalization. Un- or under-treated ADHD substantially increases risks for all-cause mortality and morbidity, including auto accidents, missed medical diagnoses, violence, etc. It's a good risk mitigation strategy for insurers if it works as advertised.
The lab I work in does some pharmacogenetics, mostly for oncology and psychiatric treatments, so I can confirm first hand pharmacogenetics isn't bullshit.
Patience_limited is 100% correct that it's pretty much all about determining whether you are a quick or slow metaboliser for each drugs, to adapt your daily dose.
We don't check for weird brain receptor or anything like that (maybe one day).
I don't know about the US, but in France there are very strict law regarding genetics, I don't think insurance can get their hands on your data (I hope you have those protection in the US).
Thanks - I'm not working in the field, but studied biochem and tox back in the long ago, and continue to follow the literature. As I mentioned above, I also have a personal reason for interest in pharmacogenomics for mental health. Both I and my insurer would be delighted to discover something cheaper that works as well for me as relatively exotic and expensive (still under patent in the US) vortioxetine...
US law around genetic data is fairly strict in the context of the HIPAA laws, but giving PHI to third parties that aren't covered entities is fraught with peril (today's example). In the U.S., a health insurer or genetics lab is a covered entity which can't share your information for any purpose other than providing care, but I have no idea what Canadian health privacy laws permit.
Canandian commercial companies (not just health) need to adhere to our version of HIPPA, called PIPEDA, which also let us ask for our data and submit corrections, and continue to apply even if our data leaves Canada.
I need to confirm with this particular company that they're willing to put in text they follow PIPEDA, and stuff like....are they gonna destroy my physical samples, can they promise not to allow access or license or sell my data, and that they won't retain anon copies after I ask for deletion, an what if they get acquired or go bankrupt etc.
I was a lot more relaxed about 23andme because aside from my sample (and entire genomic sequence) and name they don't have much . But this company will need my correct diagnoses, dosges and history etc. A lot more info.
This is purely anecdotal evidence. But I ended up titrating my dextroamphetamines down to a BABY dose of 3.75mg daily after my doctor started me on 20mg daily.
20mg is the 'standard adult dose' so I get why he started me on it. But it was TOOOOOOO MUCH. I always thought I was just a lightweight when it came to the stuff. But then one day it clicked. All the meds over the years that either hit me HARD, or didn't work at all we're all metabolized by CYP-450 2D6.
Come to find out that ≈10% of the US white population has a polymorphism for that 2D6 gene, and the 2D6 enzyme is responsible for metabolizing a ton of different drugs. Based on my experience, it turns out I'm likely an under-producer of the enzyme.
So ya, it's totally anecdotal, but I WISH they would have offered a genetic test before even starting. The original dose was simply too much, and if I happened to have an underlying heart condition, it could have been an emergency.
Side-eying your doctor for this hard. 10mg is the usual starting dose in the US for adults on Adderall, based on the experiences of a number of friends, and 20mg is a pretty high dose that it's more normal to titrate up to rather than starting with it. When I was on dextroamphetamine my psychiatrist started me on 5mg and I never needed more than that (since then I've switched to an equivalent dose of Vyvanse). Even my friend whose wildly incompetent psychiatrist prescribed her 20mg twice daily and caused her significant mental health problems as a result started at 10mg. Moreover, if it "hit you hard", a competent clinician should have asked you about that and adjusted your dose down if you were experiencing too many side effects.
If it's just the dextros it's not Adderall, but a related drug. Adderall is the mix of dextro and amphetamine. Starting dose of just dextro is usually 10-20mg for ADHD but I've seen it more as a narcolepsy drug personally (typical starting dose is 10mg there). May just be prescribing preferences though. Or that people are switching from other stimulants.
Agreed that they should have started lower and bumped up or bumped down if the impact was that negative though
Adderall is indeed composed of both isomers of amphetamine, but afaik the typical dosages don't wildly differ from pure dextroamphetamine. They are the same compound underlyingly, just two different isomers, which were explained to me by my psychiatrist as left- and right-handed versions of the molecule. The right-handed version is generally associated with most of the positive effects and the left-handed version with unwanted side effects, which is why the version with only the right-handed version is used (hence dextroamphetamine). Afaik Adderall has a 3:1 ratio of D-amphetamine to L-amphetamine.
My understanding is that Adderall is much more common and easier to get than dextroamphetamine in the US, which is why most of my friends with experience getting onto ADHD meds as adults have experience woth it rather than dextroamphetamine. The opposite was the case when I lived in Germany, which is why I started on dextroamphetamine myself rather than Adderall -- in Germany Adderall-equivalent is only available when compounded specifically and that isn't covered by health insurance afaik. Public health insurance in Germany also actually only covered dextroamphetamine itself for children, so when I switched to public health insurance I had to switch to Vyvanse anyway (and I was looking for something longer-acting at that point anyway, so it balanced out). I'm glad I started in Germany on 5mg though, because taking twice as much would've been completely unnecessary.
No they don't differ much, just providing clarity since it seemed like you were confusing the two rather than glossing over it.
As I said, the starting dose seems to range 10-20 in my search results but that could be due to switching from different meds rather than starting medication from nothing. But absolutely a good clinician should have done better with adjusting them. Idk if there's a difference in accessibility, currently Adderall is having regular shortages, but I do know someone who took dextro for narcolepsy so ¯\_(ツ)_/¯
That's a really big dosage difference. Did you see much better results after the adjustment?
So far I have never experienced any immediate difference on any ADHD medication I've tried, that's why I was thinking about trying to find out if there are reasons why I need to keep asking for something else. I hate how doctors' standard response is "according to current literature (that was compiled using probably white college aged men), what you (a small East Asian woman) report shouldn't be happening, so we will disregard your symptoms and experiences completely".
There's a great deal of variation by ethnicity. That's been entered into prescribing considerations for a while, especially in oncology and for high-risk drugs like anticoagulants. If you're a member of a population that's generally got a 25% chance of not responding at all to warfarin and you might die from a blood clot, that drug probably wouldn't be prescribed, even though there's a 75% chance you'd be fine. It's a critical enough treatment that they're not going to wait for individual genetic testing. [Recent experience with a family member...]
It's only in the last few years that individual genetic testing has gotten cheap, rapid, and specific enough to be cost-effective and meaningful. I totally get where you're coming from - I apparently don't metabolize antihistamines, related antidepressants, antinausea drugs, or benzodiazepines very well, and have had some scary side effects from standard doses.
Forgot to mention this is for a Canadian employment extended health insurance. Reading it over again this seems to cover med testing for anxiety and depression, chronic pain, and ADHD.
That's all very helpful to know, thank you for the info and links. The benefits make sense, that, if an employee isn't unwell or their loved one isn't struggling to find the right medication to manage their mental health, that translates into more productivity
As it stands, all genetic screening for psychopharmacology is exploratory. There may be some small studies with promising results, but it's all new enough to treat as a novelty for the time being. There will probably be benefits in using it in the future, but I don't think it's around the corner for anything murky at all, including ADHD.
If I'm putting on my crank cap, then I'd hazard that Personalized Prescribing is sharing data with insurers, or even willing to fudge results to give you recommendations that always correspond with the cheapest medication. Assuming there's no outright fraud, it does give insurers yet another standard to appeal to, a la "oh, sorry, we said the pharmacy, provider, and medication was covered, but we need your doctor to tell us your medical information to pay for this, just in case". But that's my perspective from the nation to your south, so maybe your insurers are slightly more trustworthy.
So this is not a specialized area of mine, here are some thoughts though.
There's some indication that the use of fMRI can better match medications to the individual. Even if your experience is "depression" but your brain looks like "bipolar" then it's possible mood stabilizers will work better than traditional antidepressants.
Genetic testing can flag some potential negative side effects: flag a gene that makes it unlikely Med A will work for you, or that you metabolize Med B in a particular way, for example.
There's not a much certainty here as they'd like, and it's certainly biased towards predominantly European genotypes and noting those differences. Idk enough to say if that makes it a bad idea for other populations or what the effectiveness difference might be.
Where does this benefit insurance companies? Possible thoughts
Hypothetically if this works they reduce the amount of trying to juggle your meds around, trying fewer meds that don't work and reducing costs by eliminating the "bad" options up front. Even if that hypothetically directs you to more expensive treatment, on average it should probably reduce the cost of bouncing around. Especially if there's effectiveness with ADHD meds, which I didn't look into specifically, this could be beneficial.
Reducing the cost of hospitalizations from not taking meds due to side effects or low efficacy. I see some indication they think they can predict suicidality. I'm less confident about that. But there may be genetic markers for chronically suicidal people that I'm not aware of, so.... Maybe. With ADHD in theory if you're treated you reduce your "I didn't follow up with the doctor about X so now I am at the ER" sorts of things.
It may be that they're getting a kickback from the companies trying to study the efficacy of the treatment (rather than really studying your genes) even if they're not disclosing that research or kickback to you. Idk the law well enough to know what disclosures are required.
My best guess
If you were struggling with meds, especially ones that might leave you suicidal or at other high risk, it might be worth a shot. If you're worried about taking a new med and the struggles of adjusting it is less worth it, but maybe still. I was so frustrated when adjusting my meds for ADHD I wouldn't say it wouldn't have been worth it.
I'm not super precious about my genes, but I don't fault anyone for feeling that way. How do they protect your genetic results and your identity if you are the only one sharing them with your doc? Does the doc just go back to the company? There's going to be privacy laws in place but stuff gets weird sometimes. I'm not sure the efficacy is high enough that I'd be interested if I weren't seriously struggling to find medication that worked for me.
As an aside I get these sorts of offers from my insurance company for diabetes. There is a benefit in making sure people with chronic conditions take care of themselves. it's just idk if this qualifies.
That makes sense, things can get wildly out of hand especially since they this also apparently covers depression and other mental health. Not diabetes, for this pharmacogenetics thing, surprising they don't. Maybe there's really only one type of treatment everyone is already on?
It's possible I've junked the mail without noticing if they've added pharmacogenetic services. But I take oral meds, not insulin. There's already a lot of ways to measure that effectiveness (A1C and home or continuous glucometer) that are less subjective than mental health meds, and maybe it hasn't been studied or shown to be efficacious yet.