Welcome to post 6, the next-to-last post in this series on gene-testing to inform ADHD drug therapy.
This blog series began with a single post in mind: Hey, wouldn’t it be interesting for both of us to get gene-tested for ADHD medications-response and to share the results with ADHD Roller Coaster readers.
By both of us, I mean me and my husband, Dr. Goat, a molecular biologist and geneticist who was diagnosed with ADHD at age 37.
But how many average folks know what is a gene variant, an extensive metabolizer, or a receptor? How many can describe the difference between an active and an inactive medication?
If most people are like me, the answer is, “not many.” If Dr. Goat and I were truly to perform a service to readers, we needed to provide for you a foundation for understanding the information provided by these tests.
Hence, a six-part blog series on gene-testing to inform ADHD drug therapy—that has now turned into 7 parts. The last post, number 6, was just too long for one sitting. So, I chopped it in half. Here is part 6, with the 7th and final post to appear next Wednesday.
Dr. Goat and I appreciate the enthusiastic response to this series, and we welcome your questions and comments.
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.
Highlighting Our Test Results: Gina’s First
By Dr. Goat
In my previous post, I shared my reactions to receiving the test results—both for me and Gina—from the testing we did via Harmonyx. (There are other testing options, including some covered by insurance; this is simply the one we chose. They are all similar. We have no business affiliation with the company, which is no longer in the gene-testing business.)
Gina took the test solely out of intellectual curiosity; she does not have ADHD.
In this post, I share the results again and delve deeper into a few highlights about what they mean.
In this post, we take a closer look at Gina’s results and next week we’ll examine mine.
According to Harmonyx, there are no obvious genetic problems with her ability to utilize all the medications in the green column (“Try these first”).
Does that mean she needs these medications or that she will derive a benefit from them? No, it absolutely does not. This test is for people who have been diagnosed with ADHD, the test itself does not make the diagnosis.
To review, for the sake of clarity:
- The genetic test is not diagnostic for ADHD
- The test does not indicate that anyone (ADHD or not) taking the test will achieve good therapeutic results from the medications in the “try these first” columns, in the sense that these medications will mitigate ADHD symptoms. For that, we look to the published literature examining the effectiveness of these medications. And we also consider individual response.
The test includes an important list of disclaimers. Here is my editorialized version of that list:
- Drugs are reported in alphabetical order: The list is not intended to imply that the FDA has approved all of these drugs for the same indication, or that they are comparable in safety or efficacy. They are not!
- The brand name is shown for illustrative purposes only; other brand names may also be available.
- 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.
- The test looks only at the patient’s genotype and its relationship to these drugs. This is another indication of the care I find that Harmonyx is exercising in communicating with patients. Because some genes influence the response to many drugs (as I’ve indicated in post 3), my understanding is that Harmonyx only lists those drugs whose effectiveness in treating ADHD is heavily substantiated.
- The presence of other drugs in the patient’s system can impact these results. This is one reason why I indicated in post 5 that other factors are at play in how a patient reacts to a medication.
- All results should be reviewed with the pharmacist and the patient’s treating physician. Do not discontinue or change any medication without the advice of the prescribing physician. This is in part because some drugs need to slowly phased out rather than abruptly dropped.
What Do Gina’s Genes Say for ADHD Medication?
Notice the “fine print” under the first column: “No genetic reason to suspect a lack of efficacy. These medications may be associated with a gene-dose effect. Please see the guidance notes below.”
What is it about Gina’s selected genes that tells us how she might react to the listed medications? The test results offer a “closer look” (see figure below), one that explains:
- the selection of the genes being tested, and
- what a patient could expect given whatever form of a gene they have.
Let’s look at one of these genes for Gina:
Gina’s ADRA2A Gene
Prevalence: 41% of patients
Phenotype: Typical Response (CG): This genotype is associated with the typical response phenotype. Based on the gene-dose effect of ADRA2A genotype and methylphenidate and the alpha-2 adrenergic agonists, patients with this genotype may respond well to these medications, but may require more careful dose titration to achieve desired response.
This would be great news—if Gina actually had ADHD.
A large fraction of the population (41%) has this form of the ADRA2A gene. It is associated with a conventional response to methylphenidate (e.g., Ritalin, Concerta). That is, a therapeutic benefit with minimal side effects is expected, at least as far as this gene is considered. Remember, there are lots of factors—well beyond this one genetic variant of ADRA2A—that influence how effective a drug is for a given patient.
The statement about “careful dose titration” is standard good advice for any drug, as we explained in a previous post.
Let’s look at another of Gina’s gene, one we explored in post 4 in the series:
Gina’s CYP2D6 Gene:
Genotype: *2/*41; 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.
Aha! Not quite perfect; one of Gina’s alleles has reduced function (I know this because I’m a geneticist, not because it’s stated in the report).
Still, in combination with the “normal” allele, it means that Gina is effective at metabolizing drugs. In other words, she is an “extensive metabolizer” – which we explained in post 4 as being the common class of metabolizers, representing the type of people for which most drugs are designed: “normal” or “extensive” metabolizers. For a refresher, see diagram below.
That’s good, because the “regular” job of this gene is to remove compounds from the blood in order to keep it clean. Given this combination, the dosage of atomoxetine (Strattera) might even need to be increased somewhat because she is so good at removing it from her blood stream.
If you’re wondering about the mysterious “CNV”, it stands for Copy Number Variant. In the interest of simplicity, here’s what you need to know about that: If you have anything other than two copies, you should speak with your physician, who will explain what consequences might be expected, if any.
Summing up, Gina has a great set of genes (among many other fabulous traits). They are so good in fact, they can serve for both of us; I can use the help!
In the next and final post 7, I delve more deeply into my own gene interpretations vis a vis ADHD medications.
Dr. Goat and Gina welcome your comments and questions.