Genetic Testing for ADHD Medication—6

gene-testing to inform ADHD drug therapy

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.

ADHD, DNA, and Predicting Medication Response

To 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.

—Gina Pera

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.

Gina

To review, for the sake of clarity:

  1. The genetic test is not diagnostic for ADHD
  2. 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 Disclaimers

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.”

HarmonyRx Results Gina_Page_1

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:

  1. the selection of the genes being tested, and
  2. what a patient could expect given whatever form of a gene they have.

 HarmonyRx Results Gina_Page_2

Let’s look at one of these genes for Gina:

Gina’s ADRA2A Gene

Genotype: CG

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.

Translation:

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.

Translation:

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.

Where are you in the metabolizer spectrum?
Where are you in the metabolizer spectrum?

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.

In Conclusion:

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.

11 thoughts on “Genetic Testing for ADHD Medication—6”

  1. Lise C. Klerekoper

    This series is excellent!! There’s nothing else out there that remotely comes close to how comprehensive this is, & I applaud both you & your obviously brilliant husband for putting it together. The material is complex & difficult for most lay people to understand/process, however, you’ve done an amazing job explaining all aspects of genetics as they relate to ADHD meds & then some. I look forward to Part 7 & finding out in more detail what Dr. Goat’s results mean as far as ADHD medication options. I have a good idea, but I can’t wait to hear about all of the details.
    I’m a therapist (LCSW) & work in a large, multi-disciplinary practice that has been using genetic screening for the last 6 years. In fact, we were an early “test site” for Genomind, but later switched to Genesight after we found out their information was more comprehensive because of a second level of testing Genesight was doing. When the FDA told Genesight that they couldn’t provide the ADHD medication information any longer (based on what you’ve already discussed in this series), we began doing additional investigation to see if there was anything else out there that could still address the ADHD piece. That’s when we ended up back with Genomind, as they had advanced their genetic screening test & were actually now offering more than Genesight. This was about (1) year ago. Specifically, the Genomind test that’s now being used does include the ADHD component. Since I’m not a physician, nurse, or scientist, I can’t speak w/ any specificity about the new Genomind test. Plus, I haven’t had a client screened with this newer test yet, (been working from home since March), so I can’t access an actual client report. What I do know is that the psychiatrists & nurse practitioners in my practice seem to like it even more than they did the Genesight. I’m sure you’re husband could look in to the current Genomind test called, Professional PGx with Rx MetaType also provided. Given how much this field is changing, who knows what is next on the horizon.

    I’ve had many, many clients, both with ADHD & other psychiatric conditions, who have had genetic screening done over the past 6 years, & I can’t tell you how beneficial it has been having the gene & medication information. I’ve had clients experience far fewer side effects, as well as a significant reduction in clients having to try multiple medications before finding a drug & dose that effectively treats their condition. Given a person’s genes will never change, the client doesn’t have to have the test repeated & this has been a real plus with clients. Also, it provides information on other medications other than just psychotropics; specifically, narcotic pain relievers & over counter pain relievers. In addition, being able to find out if a client has the MTHFR gene variant can also be critical as far as their mood/depression. I’ve seen ADHD & non-ADHD clients who have low or no activity start taking L-methylfolate, & have seen anything from a slight to significant improvement. Given this happens by just taking a vitamin/supplement, it’s pretty remarkable.

    Sorry for such a long post, but I wanted to commend you both, as well as share some additional information relevant to this series that may be helpful. It must be wonderful to be able to collaborate w/ your husband on material that is such a critical part of health care these days, & will likely be even more of a factor in treatment of both health & mental health in the future.

    1. Hi Lise,

      Thanks for the kind words – and your interest in this series. My husband thanks you for the “brilliant” modifier and says, “my wife is brilliant, too — she’s the instigator, writer, fact-checker, and synthesizer.” 🙂

      And thank you for so diligently serving the ADHD community. We need more of you!

      I’ll have another look into Genomind. The last I checked (a couple of years ago), it differed little from Genesight in the overall approach. A quick search now shows that Genomind is heavily promoting itself and had done some tangling with the FDA. This is a high-stakes, potentially highly lucrative market—especially if there’s approval for Medicare. I learned about this during my initial research.

      Don’t mind me while I update my knowledge base. 🙂

      The fact that the FDA had to rein in Genomind still gives me pause about its scientific rigor. The FDA makes solid arguments against the over-selling of these tests here:

      https://www.fda.gov/medical-devices/safety-communications/fda-warns-against-use-many-genetic-tests-unapproved-claims-predict-patient-response-specific

      From what I can tell, there still is little solid research (especially that including controls).

      To be sure, I don’t doubt your clinical observations. Skillfully used, these tests do have some utility. But the trouble is that they are seldomly skillfully used, in my observation. Real research is needed, including blind controls.

      MTHFR, in addition to being a legitimate medical issue, has unfortunately also been quite an over-hyped fad. I was an early adopter but have seen how it’s gotten out of hand — as most things do on the hustling end of the Internet. Many people want to believe that their mutations explain what are actually their ADHD symptoms — and are loathe to let go of it, with some aggressively pushing methyl-folate doses. It’s a good idea for most Americans to take methyl-folate products. Especially given that most don’t eat enough folate-containing foods—and many are over-loaded up with folic acid from standard multi-vitamin/mineral supplements. More about that here:

      https://www.psychiatrictimes.com/view/weighing-benefits-genetic-information-clinical-psychiatry

      As that article also states (2017 but doesn’t seem outdated)—and is our major point in the series—the tests are perhaps most useful in identifying rapid/normal/slow metabolism issues. If more prescribers followed the “start low, titrate slow” method, this wouldn’t be as critical an issue. But many do not. They simply decide that medication doesn’t work for the patient.

      I find it especially worrying, as this Genomind exec points out, that the testing is more often used in treatment-naive pediatric patients.

      https://www.psychiatrictimes.com/view/weighing-benefits-genetic-information-clinical-psychiatry — Excerpt:

      According to Daniel Dowd, PharmD, Vice President of Medical Affairs at Genomind, one of the two leading commercial pharmacogenomic services, close to 5000 clinicians are currently using Genomind’s panel, and the company has recently logged its 100,000th test. “What we’re actually seeing in practice is most psychiatrists are ordering this for the treatment-resistant patients with 2 or more treatment failures,” says Dr. Dowd. “But in the pediatric patient population, they’re more likely to order it for treatment-naive patients.”

      In fact, my hearing reports from parents about their children “not being able to take stimulant medication’ raised the initial red flags years ago. This should not still be happening. There are huge opportunity costs here.

      https://www.genengnews.com/insights/treading-with-caution/ Excerpt:

      In September, The Association for Molecular Pathology (AMP) published a position statement for pharmacogenomic testing that spells out “best practices” criteria for laboratories to follow. AMP recommended that labs report drug-gene associations that are “robust and supported by strong scientific evidence in the peer-reviewed literature, in the FDA-approved drug label, and/or in clinical practice guidelines.”

      AMP said pharmacogenomics test reports should include a statement of a patient’s metabolizer status as determined by the genotype and a list of the drugs that may be impacted by this genotype, as well as alternative dosing or treatments that doctors may consider. Patients should discuss their pharmacogenomics test result with their healthcare provider to determine if changes to their medication plan are warranted.

      Sorry to go on. This is a complex topic, and I’ve just written the module on ADHD and genetics for my online training. The complexity is just mind-boggling.

      Thanks for your comment and report from the front lines. How wonderful to work at a “multi-function” clinic, with MDs, therapists, etc. I wish there were more such clinics!
      g

  2. I read your whole series of posts, and have a better understanding of how genetics can impact the efficacy of medication. Thank you!

    I had genetic testing done, hoping it would offer possibilities for medications for my diagnoses of depression and anxiety. I was then diagnosed with ADHD (which I believe explains my decades-long ineffective search for the “right” meds).

    My results report isn’t particularly relevant in terms of listing potential appropriate medications. Any suggestion for medications to manage ADHD that may be a good fit for me?

    CYP1A2 Ultrarapid metabolizer, CYP2D6 Intermediate Metabolizer, UGT2B15 Intermediate Metabolizer, and the rest of those tested were “normal.” Thanks for your writing, and thanks in advance for any insights you might have into my particular situation!

    1. Hi Laura,

      Thanks for reading the series….I worked so hard making everything understandable by laypeople (like me!). Still have some kinks to work out.

      When it comes to medication treatment for ADHD, we know what works for the majority of people: stimulant medications are the first-line choice.

      As to your specific mutations, that can inform dosage and frequency. So, if you take a medication that is metabolized by the CYP1A2 for example, you might need a higher-than-average dose. Depending on the medication! (We wrote about active and inactive drugs.)

      But, as we wrote in the series, for most people it is irrelevant to basic ADHD medication treatment.

      I encourage you to read the basic protocol in my first book. It’s not rocket science but amazingly few prescribers follow anything close to a method. That’s why it’s up to us to self-educate and self-advocate.

      Here is a link to Amazon:

      https://amzn.to/3edheEQ

      FYI : Drugs that CYP2D6 metabolizes include selective serotonin reuptake inhibitors (SSRI), tricyclic antidepressants (TCA), beta-blockers, opiates, neuroleptics, antiarrhythmics, and a variety of toxic plant substances.

      CYP1A2 contribute to the metabolism of therapeutic drugs including caffeine, clozapine, olanzapine, amitriptyline, R-warfarin, verapamil, theophylline, propranolol, clomipramine, imipramine, haloperidol, and acetaminophen.

      I hope this helps!
      g

  3. In an effort to find some help I have stumbled across your fantastic information. I have been diagnosed with BED (binge eating disorder) and the treatment that my psychiatrist wants to use is medication used to treat ADD/ADHD.
    I had gene mapping done several years ago after taking various medications for depression with no results, finding out my CYP2D6 was almost not performing at all. That was helpful in getting me on the right medication for depression, but with my new diagnosis, we are struggling.
    Can you tell me in simple terms if there are medications for ADHD for those with low functioning CYP2D6?
    I read the part about you could try to give a higher dose and all that but still wasn’t clear on a certain medication.

    1. Hi Rhonda,

      Kudos to your psychiatrist! Check out my post on ADHD and obesity: https://adhdrollercoaster.org/tools-and-strategies/can-adhd-make-you-fat/

      As for your question: “Can you tell me in simple terms if there are medications for ADHD for those with low functioning CYP2D6?”

      As far as I know, this would mean that you might not do well with Strattera (approved for ADHD treatment but, in my experience, not as helpful as the stimulants for most people). It is primarily metabolized through the CYP2D6 enzymatic pathway.

      But the stimulants (first-line treatment for ADHD) are not.

      https://www.ncbi.nlm.nih.gov/books/NBK315951/

      In other words, a stimulant such as Ritalin, Vyvanse, or Concerta might be the best bet for you.

      Good luck!
      g

    1. Hi Betty,

      Yes, I need to update all the posts to reflect the update.

      I would not say that Harmonyx is “being investigated by the FDA.”

      Rather, the FDA has a problem with these direct-to-consumer tests in general, such as 23andMe. Along with Harmonyx, there were two other companies.

      It is complicated, the reasons why this is happening. I’ll try to be clear and succinct.

      It’s a shame. The testing is very helpful. But, the entire reason we wrote this series is because too many patients (mostly parents of kids with ADHD) were mis-interpreting the results from not only this test but Genesight’s and others (and that is FDA approved, apparently). Then again, so were their doctors.

      Stay tuned.
      g

    2. Hi Betty,

      I need to research current options.

      It might be that Genesight’s test is the only option now. I don’t know.

      It is roughly equivalent to the Harmonyx testing, but there was one aspect to it that my husband didn’t find as well-supported in the science. Just one genetic variant, I think. Probably a minor issue.

      https://genesight.com/patients/genesight/adhd/

      g

  4. Pingback: ADHD, DNA, and Predicting Medication Response: Part 1 - ADHD Roller Coaster with Gina Pera

Leave a Comment

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.

Stay in Touch!
Ride the ADHD Roller Coaster
Without Getting Whiplash!
Receive Gina Pera's award-winning blog posts and news of webinars and workshops.
P.S. Your time and privacy—Respected.
No e-mail bombardment—Promised.
No Thanks!
close-link