Welcome to the final post in this series on genetic testing for ADHD Medication. My husband, Dr. Goat, and I greatly appreciate your enthusiastic response.
We based this series on testing that is is no longer available. But the currently existing tests are very similar.
The overriding message is this: Be careful about physicians misinterpreting these genetic testing results. Your or your child’s appropriate treatment relies upon being a smart consumer.
Moreover, you needn’t be interested in this testing at all to learn a great deal from this series!
ADHD Gene Testing Series in Seven Parts:
Here is a summary of the previous posts (click on the blue number to link to the article).
1 Provides an overview of genetic testing as it relates to ADHD medication-response.
2 Shares testing results for my husband and me, along with my husband’s personal reactions to our disparate genes.
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.
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).
5 Reminds us 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.
6 Looks at the specifics of Gina’s testing results, the same way this 7th (and final) post looks at Dr. Goat’s results.
Highlighting My Test Results, 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 Point: Strattera (atomoxetine)
I am indeed taking Strattera, the sole drug recommended under the “Try these first” category. But I’m taking it at a much 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.
Gina would like to pipe in for a second:
Note that the third (try these last) column includes the first-line treatments for ADHD: the stimulants! It also includes some down-the-line medications sometimes used for ADHD but often with stimulants.
This is an excellent example of how the testing in no way takes into account which medications are most likely to be effective for the condition being treated.
The list of disclaimers includes:
- The prescribing physician should review the prescribing information for the drugs being considered and make treatment decisions based on the patient’s individual needs and the characteristics of the drug prescribed.
- This test looks only at the patient’s genotype and its relationship to these drugs.
Second Point: Wellbutrin (bupropion)
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.
Here are the guidance notes for this particular “menu”:
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. (To see a larger version, click the image below.)
Dr. Goat’s 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 post 4, 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 the sausage-maker stuffing meat 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 exist for dealing with it (e.g. higher dosage).
As I said before, we all have semi-crappy genes. I sure Gina has some unsavory genetic variants in her genome … somewhere.
Dr. Goat’s 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.
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:
Dr. Goat’s 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.
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. Does genetic testing for ADHD Medication provide vital information? Maybe, if you have some unusual mutations or you are a very rapid/slow metabolizer. That is useful information. But this the best way to identify optimal medication? No. Absolutely not.
Remember: Only One Piece of the 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. To be notified when they are ready, please be sure to subscribe to my blog.