View Full Version : Genetic testing to predict medication response?


sarahsweets
07-27-16, 02:42 AM
[MODERATOR NOTE: Split from a thread on methylphenidate dose (http://www.addforums.com/forums/showthread.php?t=170552).]
Gene sight. I have had it done! The ritalin family of drugs will have less effect. It says I am either a slow metabolizer or ultra rapid at the enzyme where amphetamines are metabolized. It also says I have a lower effect from some ADHD medications. In addition, this affects my aripiprazole and wellbutrin dosages.

I know I have an ultra rapid metabolism of these types of medications because I get no effect at all from them, even at max of the "recommended" dosages.

if you can get the testing, get it! it is really informative and I have done a bunch of research based on my results.

Amy
I am not trying to argue here but have their been studies or tests to confirm these tests are accurate? Like, are other medical professionals basing their prescribing habits on these tests?
Are they given in a lab or under a doctor's supervision?

namazu
07-27-16, 03:44 AM
I am not trying to argue here but have their been studies or tests to confirm these tests are accurate? Like, are other medical professionals basing their prescribing habits on these tests?
Are they given in a lab or under a doctor's supervision?
The GeneSight tests are accurate in detecting known variants in ~12 [?] genes that studies have linked to metabolism of medications or their handling in the body.

Their ADHD-specific test looks at only 3 genes: Cytochrome P450 2D6 (CYP2D6 (http://omim.org/entry/608902)), Catechol-O-Methyltransferase (COMT (http://omim.org/entry/116790), and the Alpha-2A Adrenergic Receptor ADRA2A (http://omim.org/entry/104210).

There's solid evidence that CYP2D6 allelic or copy number variants (what version of the gene you have, and how many copies) can have a big impact on the way drugs are metabolized, and a wide range of medications are affected. The gist: Some people are poor metabolizers (which often means they need lower and/or less frequent doses, because the stuff doesn't get eliminated and sticks around in the body). Others are ultrarapid metabolizers (so the stuff is eliminated from the body really quickly and people may need higher and/or more frequent doses). Most people are somewhere in the middle.

There have been some studies looking at associations of COMT and ADRA2A variants with LDs and several mental illnesses, often with mixed or conflicting results (sometimes due to small samples, different subjects, etc.). Here are some studies looking at ADRA2A and response (http://www.ncbi.nlm.nih.gov/pubmed/?term=adra2a+polymorphism+adhd) to methylphenidate (Concerta, Ritalin, etc.) and atomoxetine (Strattera), and others looking at COMT (http://www.ncbi.nlm.nih.gov/pubmed/?term=comt+polymorphism+adhd).

There are some hints that variants in these genes may be related to medication response, but in my opinion, the evidence for effects of these genetic variants on medication response is weaker and the interpretations are less clear than for CYP 2D6.

GeneSight also has tests for other genetic variants linked to psychotropic drug response, and for the MTHFR gene (involved in folic acid processing).

In my opinion, these tests could potentially be useful for some people who've had extreme reactions to medications or who have had a lot of trouble finding meds that work consistently or without problematic side effects.

That said, these tests are also heavily marketed, and (in my opinion) hyped beyond their actual utility. They have some studies suggesting that these tests save the healthcare system money and make the process of troubleshooting meds more efficient. There may be some truth to it, but the evidence isn't yet strong -- if it were, you can be sure psychiatrists and HMOs would be lined up to use it! There's uncertainty about how strongly or consistently the tested gene variants are associated with medication response (alone or together), and there are a lot of genes and body chemistries that probably influence things that we don't know about or understand yet (and thus don't test for). So the testing certainly has its limitations.

For what it's worth, I have had this testing done myself, and for me it didn't provide any useful information. At the clinic where my pdoc and psychologist work, there was a guy whose tests suggested he should respond poorly to a certain medication -- and that medication turned out to be the only one that worked well for him. (Go figure!)

That said, if you're someone who is an ultrarapid metabolizer or poor metabolizer due to a CYP 2D6 variant, that could be useful to know.