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How useful are these genetic tests which tell you how a patient metabolizes certain medications? I've seen some patients who have had such tests done, and they receive reports grouping medications by how well the patient might respond. Recently I also heard a presentation from someone who does pharmacogenomic testing. These tests are said to predict which medication is the "right one" for a particular patient, so they can avoid spending hundreds or thousands of dollars on medications which don't work for them.

My understanding, however, is that these tests can only tell you how rapidly or slowly a patient metabolizes various medications... not whether a certain one will be effective. I can see this being useful for determining which dose to prescribe, but as far as what is actually going to help the patient, I believe it's still best determined by trial and error. Also, regardless of how rapidly someone metabolizes a medication, my approach to prescribing would still be to start with a low dose and titrate up until I find the lowest effective dose.

Is my understanding of pharmacogenomics correct? Does anyone order these tests and find them to be helpful? I'm just wondering if it's worth ordering a test prior to prescribing anything, to avoid wasting time with Prozac, Zoloft, and Effexor if it turns out that Cymbalta is the magic pill, for example.
 

MacDonaldTriad

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These test tell us nothing about pharmacodynamics, and nothing about effectiveness. Pharmacokinetics involves the absorption, distribution, metabolism and elimination. All you will get is some information about the metabolism part and a bill.
 

hamstergang

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I never order this test. The concept doesn't really make sense as you've said, and the only studies I saw on looking at if such testing improves outcomes were performed on adults with depression, and those weren't terribly convincing. Any other age group or condition is untested as far as I know.

However, they do tell us more than just pharmacokinetics. They tell us about MTHFR, which is proving to be more and more useless as studies come out. They also tell us about genes for a serotonin transporter (?), some allele of which has been associated with less likelihood of SSRI response in depression. Since we never otherwise test for this, I believe it's not nearly clinically useful enough.
 
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Armadillos

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I haven't ordered yet, but in my state Medicare(?)/Medicaid and atleast one major insurer pays the entire price of one of these panel of tests. One of these days will look up the studies they must have used to get this thing paid for, my understanding is they have been published less than 6 months and are somehow more impressive than the stuff from the last few years.
 
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wolfvgang22

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The cover article of last months Psychiatric Times newsletter gave a decent summary regarding these tests.
 
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HarryMTieboutMD

Really the only strong evidence is for CYP450 metabolism. Anything pharmacodynamic is pretty much worthless. If you know your pharmacokinetics basically this test will tell you what you are probably already guessing. For example, I have a patient with an unspecified SCZ (long story but I think he's bipolar with recurrent episodes of psychotic depression) who is getting better on Zyprexa+prozac (he was discharged on zyprexa, I added the prozac after I reviewed the history) and had plenty of psychosis on 20mg Zyprexa after 1 month. I then increased to 30 and then 40mg with almost complete resolution of psychosis. Knowing that Zyprexa is metabolized mostly by CYP1A2 and minimally by 2D6 (and lit review doesn't seem to suggest that added prozac changes Zyprexa levels significantly via 2D6 inhibition) my leading hypothesis is that the patient was a CYP1A2 fast metabolizer. I *could* get testing to confirm this, but would it change management? NO! Unfortunately he started smoking again so his psychosis isn't completely cleared (again likely combination of fast metabolizer and induction of 1A2 via polyaromatic hydrocarbons from tobacco smoke) and he's refusing pharmacotherapy/not responding to MI/wont enroll in a study we have going on where he would get paid/meds for free :/

Because medicaid pays for it, I have ordered it a couple of times on patients who had a ton of antidepressant trials in the past but were unsure about dose/duration/response and weren't really responding to anything I was trying. This was a shot in the dark and didn't really provide useful information.
 

Liquid8

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I’ve never felt these tests to be necessary. If patients truly are fast metabolisers then it’s possible to pick it up on clinical grounds. If the medication prescribed is taken once daily, and they suffer from acute withdrawal symptoms shortly after taking it, they could be a fast metaboliser. Dividing the dose may result in better tolerability and confirm your hypothesis without the need for a test.
 
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Ollie123

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In general, the precision medicine/pharmacogenetics research isn't looking great right now. Only a handful of clearly positive studies and some of those are things you likely aren't dealing with in practice (e.g. nicotine patches for smoking cessation). Not a prescriber so can't comment on what practice standards are (though replies above suggests agreement), but I'd say as of right now its mostly a tool for companies to make money and well-intentioned but poorly-informed practitioners to waste their time and others money.

I say this as someone currently working on a pharmacogenetics grant application to NIH. So I do think there is hope for the future oin this arena. I just don't think we are anywhere near close enough for this to be integrated into mainstream clinical practice.
 

clausewitz2

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There is some evidence that topamax can be an effective tool for reducing heavy drinking days if and only if the person in question has a particular GR1K polymorphism:

http://ajp.psychiatryonline.org/doi/abs/10.1176/appi.ajp.2013.13081014

In that study none of the participants in the tested subsample had a response greater than the placebo if they did not have the allele of interest whereas the ones who had it did separate from placebo in a fairly convincing way. So, if you really wanted to, you could predict whether someone would get benefit out of Topamax in helping to curb their alcohol consumption, but why this is superior to just trying them on Topamax for a bit is not clear to me unless this genetic test becomes exceptionally cheap.
 
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I'm posting in this thread again because I have a new patient for whom I am actually considering genetic testing.

This is a patient I inherited from another psychiatrist who recently left our practice, and I have concerns about the medications he is taking. The patient is a 9-year-old boy and weighs 27 kg. He takes reasonable doses of Prozac and Seroquel, but I am worried about his ADHD medications. He has been taking Vyvanse 70 mg QAM, Adderall 10 mg QPM, and clonidine 0.1 six times daily. His mom was hoping I would increase his clonidine to further help with his impulsivity, but I said that the current dose was as high as I felt comfortable going, and that I really didn't even feel comfortable with it at the current dose.

Surprisingly his vital signs look great. But I am worried about the potential effects these medications are having on his cardiovascular system. He had an echocardiogram done within the past year to rule out any heart problems, due to his high-risk medication regimen; fortunately everything was found to be normal.

Based on clinical grounds, this is a patient which I suspect may be a rapid metabolizer of his ADHD medications, and perhaps genetic testing is not necessary to confirm this. It's just that I haven't encountered a young child before on these medications with doses this high, and despite the cardiac testing which has been performed, I still worry about him having a cardiac event someday. Also, assuming that he will be like most kids and require increasing doses as he gets older, I wonder what kind of doses he'll be on as an adolescent.

What are your thoughts on this? Would there be any benefit to doing genetic testing in a case like this?
 

hamstergang

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The patient is a 9-year-old boy and weighs 27 kg. He takes reasonable doses of Prozac and Seroquel, but I am worried about his ADHD medications. He has been taking Vyvanse 70 mg QAM, Adderall 10 mg QPM, and clonidine 0.1 six times daily.
My first thought is to be sure you know what you're treating (you may, it's just not here) given the use of so many meds. There are certainly times especially with the ASD population that behaviors get so harmful/dangerous that it seems unsafe not to try some strange medication regimens on top of the behavioral approaches hopefully being implemented. But since you weren't the one to start this, it's worth checking the other guy's work.
 
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Shikima

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Neuropsych testing for PDD and/or ADHD to help elucidate out how his brain is working without medication?
 
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PistolPete

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Yea, agree with above. My first thought was "why the heck is this kid on clonidine six times daily?" My second thought was if the diagnosis is correct.

I'd consolidate the clonidine and only use one stimulant. If he's still highly impulsive and you're sure he has ADHD, then try something other than clonidine. Maybe consider a mood stabilizer and/or a different stimulant.
 
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RKBrumbelow

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The CYP450 issue is a pretty big one. About 20% of the population is either a rapid, slow or non metabolizer for one of those metabolic pathways. The other one is MTHFR. Should you do it at the outset? Maybe the cost for the test is close to 2mo of an anti-depressant. You should at least know what to look for though. If a patient cant metabolize folic acid (mthfr) then you put them on deplin or l-methyl folate and that issue is gone and they can make their own NTs again. If they need an ssri/snri etc and they are not fully responding, cyp450 alleles could direct you to a different med. So maybe you save it for refractory patients only, but if either of those two issues is the patients problem, that genetic test is going to save them months of suffering.
 

hamstergang

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If a patient cant metabolize folic acid (mthfr) then you put them on deplin or l-methyl folate and that issue is gone and they can make their own NTs again.
Is there evidence that supplementing with l-methylfolate helps in a depressed patient with an MTHFR gene mutation and normal serum homocysteine?
 

Armadillos

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Is there evidence that supplementing with l-methylfolate helps in a depressed patient with an MTHFR gene mutation and normal serum homocysteine?
My understanding is there is no research at all specifically looking at l-methylfolate use in pts with mthfr mutations, isn't it just an assumption that these are the folks who get benefit from l-methylfolate?