Welcome to the final post in this series on gene-testing to inform ADHD drug therapy. Dr. Goat and I greatly appreciate your enthusiastic response.
Note: We have no business relationship with Harmonyx Diagnostics, the testing that we chose in order to illustrate this blog series with our own results.
We chose this particular test because:
- It didn’t require a physician to order it
- It was reasonably priced at less than $100, and
- My husband vetted the genetic science on which it is based (though not the manner in which medications are ranked in the three columns; that’s a different thing entirely).
[Update: The Harmonyx testing, made available via drugstore pharmacists, was later restricted by the FDA. Other labs offer similar testing by prescription from MD. One is called Genesight. These blog posts are pertinent to any type of gene-testing that claims to inform ADHD drug-response.]
The information in this series should help you understand any similar test’s results, even for conditions beyond ADHD.
ADHD Gene Testing Series: A Recap
Part 1 provides an overview to the topic of genetic testing as it relates to ADHD medication-response.
Part 2 shares testing results for my husband and me, along with my husband’s personal reactions to our disparate genes.
Part 3 defines what is meant by the term genotyping test. Briefly, it’s a test that informs you of your genetic particulars. Specifically for our purposes in this blog series, it refers to tests that identify which variants of the drug-response genes known to be associated with ADHD medications that you have.
Part 4 explains how, when, and why this data might prove helpful, delving more deeply into the topics of pharmacokinetics (what your body does to the medication) and pharmacodynamics (what the medication does to the body).
Part 5 reminds that genotyping data provides only one piece of the puzzle. There are many other factors that can affect how well a medication works for you, including overall health factors and co-existing conditions.
Part 6 looks at the specifics of Gina’s testing results, the same way this 7th (and final) post looks at my results.
Highlighting Our Test Results: Dr. Goat’s
By Dr. Goat
There I was, confronted with these unsavory results. After years of pontificating professionally, in the abstract, regarding how pharmacogenetics data should be used, I was now faced with getting off my academic high horse and acting on my own “data.”
Acting on this data proved challenging for one reason in particular: Contrary to the intent of this test—which is primarily intended to guide first-time users of a medication—I had already tried several of those medications over the years, finally coalescing on a “combo” that is probably close to optimal for me.
And guess what? Turns out that my combo disagrees fairly strongly from the test’s recommendations. Does that mean that the test is wrong? Not at all.
First, I am indeed taking Strattera, the sole drug recommended under the “Try these first” category. But I’m taking it at a lower-than-average dose.
As for the drugs in the “Try these last,” column, the test may well be right indicating that they are not optimal for me. But … I was already taking one of these. In short, I have no way to tell without experimenting, and that’s something I don’t want to do unless I have strong reasons to do so. Experimentations can be very disruptive personally and professionally, so I am reluctant to mess around with what seems to be working.
Second, I was prescribed Wellbutrin early on (listed in the second column), but only after I had started taking a stimulant. Plus, my physician at the time prescribed 300 mg right off the bat. The result had me flat on my back on the sofa, for two days—a prime example of the importance of slowly increasing dosage.
That was the last time I didn’t “start low, titrate slow,” no matter what the prescribing doc said. Gina had enough of physician recklessness by that episode, and she stood firm. It took me a while to join Gina in questioning my MDs, to realize that having a medical degree—and, further, being a board-certified psychiatrist—did not necessarily mean that the prescriber would be all that, well, smart. Or even careful.
Now Let’s Take a Look at My Results:
1 Patients with this genotype are less likely to respond to alpha-2 adrenergic receptor agonists [e.g. clonidine, risperidone]
2 Patients with this genotype are less likely to respond to the amphetamines. Consider using medications from another class to achieve desired therapeutic outcomes.
3 Patients with this genotype at ADRA2A are less likely to respond to methylphenidate. Patients with this COMT genotype are less likely to respond to methylphenidate.
4 Use with monitoring. Patients with this genotype may benefit from higher total daily dose (TDD) of bupropion, ranging from 320mg-420mg/day if suboptimal response at lower dosing.
5 Extensive metabolizers may show appropriate response to atomoxetine at the higher end of the recommended dose range.
Taking The Results One By One
Let’s review the printed information on the first gene, and I’ll follow with a translation.
Your ADRA2A Gene
Prevalence: 48% of patients
Phenotype: Reduced Response (CC): This genotype is associated with the reduced response phenotype. This patient is homozygous for the C allele of the 1291G>C polymorphism in the adrenergic alpha-2A receptor gene, which decreases binding affinity at the alpha-2A receptors. Patients with this phenotype may show a reduced response to methylphenidate and the alpha-2 adrenergic receptor agonists.
Translation: Aargh, this means I’m walking around with a semi-crappy ADRA2A genotype.
Remember our post about pharmacodynamics? This genotype means the functionality of the protein produced by the ADRA2A gene, namely, the adrenergic alpha-2A receptor, is a bit wonky.
As such, it reduces the effectiveness of this receptor’s interactions with a number of stimulant drugs as well as the alpha-2 adrenergic receptor agonists (e.g. clonidine and guanfacine).
In other words, and in keeping with the analogy I used in that post, the “Big Gulp” of these medications is only loosely fitting in my cup holder (receptors), such that I might want to consider a higher dosage of the drug. And remember: this is only as far as this particular gene is concerned (there are many other factors beyond this one gene!)
I would also have to take into account any other drug I might be taking. Why? Because all drugs are metabolized to be ultimately removed from the body.
Think of meat being stuffed down the sausage machine. It’s possible to over-feed that machine, at which point bad things can happen. That’s why your physician and pharmacist should always be consulted before making such changes.
My semi-crappy receptor is not completely trivial. But obvious strategies for dealing with it do exist, e.g., taking a higher dosage.
As I said before, we all have semi-crappy genes somewhere in our genome. I sure Gina has some unsavory genetic variants in her genome … somewhere.
Your CYP2D6 Gene
Genotype: *1/*1; CNV=2
Prevalence: 77% – 92% of patients
Phenotype: EM: This genotype is associated with the extensive metabolizer phenotype. When considering half-life and area under the curve (AUC) of atomoxetine in CYP2D6 extensive metabolizers, patients with this phenotype are likely to respond to atomoxetine, but may require doses at the higher end of the recommended range.
Notes: Yeah! A decent genotype for once! This is the most common form of this gene (that’s what the “*1/*1” means), such that the protein is very effective at metabolizing drugs (“extensive metabolizers” – see previous post).
As with Gina, I might benefit from increasing the dosage of atomoxetine (Strattera) somewhat. So I guess this fits with my benefiting from Strattera, which appears to be the case.
Just for fun, let’s look at one more of my genes:
Your CYP2B6 Gene
Prevalence: 48% African Americans, 25% Asians, 38% of Caucasians
Phenotype: IM: This genotype is associated with the intermediate metabolizer phenotype. Based on ability to metabolize bupropion to hydroxybupropion (HB), patients with this phenotype, who show a 20% decrease in HB levels, are likely to benefit from a higher total daily dose of bupropion.
Translation: Boo, another semi-crappy genotype. Oh well.
The interesting thing is that bupropion (Wellbutrin) might be a useful medication for me after all. As I previously mentioned, I did try it years ago, but only after I was already taking a stimulant—and starting at too high a dose. Perhaps that’s why it wasn’t beneficial at the time. In other words, this medication never got a fair shake. It’s useful to know that I might benefit from this drug.
And there you have it, folks: Mostly everything you need to know about interpreting gene tests to inform ADHD medication choices.
Remember: This is one piece of the medication-choosing puzzle
There are other puzzle pieces, including the huge number of published studies examining the overall efficacy of ADHD’s first-line medications: namely, the stimulants and Strattera. There is no “silver bullet” in finding the best medication(s), at the best dose for you. But there is a relatively straightforward “trial and error” method, as described in my book, “Is It You, Me, or Adult A.D.D.?”
In the coming year, I will be offering Adult ADHD-related webinars for therapists and the public. They will cover medication and more. If you want to be notified when they are ready, please be sure to subscribe to my blog.