Part 2: Genetic-Testing for Choosing ADHD Medications

Genetic-Testing for ADHD medications

Can genetic-testing help us to choose ADHD medications? That is the topic of this 7-part blog series.  The answer is, “it depends.”  For sure, though, the tests typically misunderstood—to often dangerous effect. That is, people with ADHD do not receive the treatment they deserve.

My husband, “Dr. Goat,” and I share many interests, tastes, and preferences. Still, we are very different individuals. Anyone who knows us can attest. But when the proof of our differences shows up in the genotyping, well, that’s science.

I’ll let him tell you the rest of the story here in part 2 of the ADHD Roller Coaster series on Gene-Testing to Inform ADHD Drug Therapy.  If you missed it, here is part 1.

Personal Introduction: ADHD Drug-Response Genotyping

By Dr. Goat

Dr. Goat and Gina Pera, Adult ADHD ExpertRecently, Gina and I explored the brave new world of genotyping – specifically, the genetic testing developed by a company called Harmonyx.  Their testing aims to tell you which of 9 ADHD medications might be the best bets for someone with ADHD. There are other tests, but this is the one we picked for this purpose.

[Update: The Harmonyx testing, made available via drugstore pharmacists, was later restricted by the FDA. Other labs offer similar testing by prescription from MD. Two companies that might offer this are Genesight and Genomind.  These blog posts pertain to any type of gene-testing purporting to inform ADHD drug-response.]

(We have no business relationship with the company. No one is paying us to write about this testing. This information should apply equally to other tests that target ADHD medications.)

I have ADHD, but Gina does not. She took the test out of curiosity—and to see how her results might differ from mine.

Completing the test was simple enough. I opened the envelope, filled out a brief form, dabbed a Q-tip in each side of my mouth cheek, shipped it off to the lab in the envelope provided—and forgot completely about it.

Initial Queasiness About Results

When we received the results a few days later—a PDF via e-mail—I felt, well, just a bit queasy.

First, some background about why this testing was doubly interesting to me.

I am a geneticist with deep professional familiarity with the field of pharmacogenomics (that is, how genes influence our response to medication). Moreover, I have been treated with ADHD medications for more than a decade. So, receiving these results provided a most interesting and novel experience. Novelty is an increasing rarity in my mid-mid-middle age.

In this blog series’ future posts, you’ll find a more scientific and practical explanation of what this genotyping business is about. To summarize here briefly, the intent of this testing is to give you an idea of:

1.    Which drugs you should consider to treat ADHD
2.    And in what order, and
3.    Give you hints about dosage.

The Four Genes And Nine Medications

The genetic testing for choosing ADHD medications does that by assessing what particular variations you have in a small number of genes known to influence response to the medications often used to treat ADHD.  These are the genes:

  1. CYP2B6
  2. CYP2D6
  3. ADRA2A
  4. COMT

The Harmonyx Test for ADHD (now unavailable) and others covers the following medications —brand name(s) following the generic name:
1.    amphetamine salts: 
Adderall
2.    atomoxetine: 
Strattera
3.    bupropion
: Wellbutrin, Budeprion, Burpoban, Forfivo
4.    clonidine: 
Catapres, Kapvay
5.    dexmethylphenidate: 
Focalin
6.    dextroamphetamine: 
Dexedrine, ProCentra, Zenzedi
7.    guanfacine
Intuniv: Tenex
8.    lisdexamfetamine: 
Vyvanse
9.    methylphenidate
: Concerta, Daytrana, Metadate, Methylin , Quillivant™, Ritalin

Face to Face with My Own Crappy Genes

As it turns out, I have a bunch of semi-crappy genetic variants. As such, they somewhat compromise the effectiveness of many of those drugs for me.

Now, there’s nothing terribly bad about my testing results, thanks for the concern. But hey, I definitely don’t have top-of-the-line genes in this department. (Nor, by the way, do I have the worst.)

In a way, that’s just fine, because everyone has crappy gene variants somewhere in their genome. The genome is the collection of all genes. If you watch NOVA’s Cracking the Code of Life, you know that genes are present in nearly all cells in the body. They constitute the “instruction book of life.”

As it turns out, I have

a bunch of

semi-crappy

genetic variants.

In addition to somewhat compromising my ability to benefit from many of these drugs (seven out of the nine listed in the results, sigh), I have a suspicion: At least one of these variant genes may well contribute to my having ADHD in the first place.

Harmonyx claims nothing of the sort, however. At this point, the science remains nascent about identifying the specific causative genes for ADHD. Even though we know ADHD is heavily genetic, we have only a vague idea of which genes exactly may be involved.

I conversed with the Harmonyx CEO and a number of their folks. And it was clear to me they are trying their best to make the whole process as evidence-based as possible—meaning, sticking to what has been established in the scientific literature. That includes selecting which genetic variants to genotype.

You would think that basing a medical test or intervention on published data would always be the case in medicine. But in fact, it is frequently—perhaps mostly—not the case. Lots of stuff gets done and said in medicine without anything approximating real data to back it up.

 

Harmonyx ADHD test
Dr. Goat’s Test Results Click to see larger image

Now, back to me.

There I was, confronted with these somewhat unsavory results. For years, I had pontificated professionally, always in the abstract, regarding how pharmacogenomics data should be used. Suddenly, I was  faced with getting off my academic high horse and acting on my own “data.” How I might do that will be the topic of a future post.

Turning to Gina’s Results

A second, and most interesting, aspect—at least to me: the genotyping results for Gina.

HarmonyRx Results Gina_Page_1
Gina’s results. Click to view enlarged.
Harmonyx ADHD test
Gina’s Results, part 2

 

No, Gina doesn’t have ADHD. Indeed, she is very far from the ADHD phenotype. (Briefly, this term refers to the expression of a genotype in the form of traits that can be seen and measured, such as hair or eye color—or not having ADHD.)

As far as the genes related to ADHD medication-response in this test from Harmonyx and others, she has no semi-weirdo variants. Damn it!

We were both struck by the difference in her results versus mine.

And you know what? My initial knee-jerk chimpanzee reaction was one of visceral envy for her genes—to the point that had I not been a highly evolved member of Homo sapiens sapiens, I would have gladly pi**sed on her printed results just to even the score.

ADHD and genotyping for medication
Dr. Goat, reacting to Gina’s test results

But as I’ve already said, so what? She’ll have “deficiencies” in other genes somewhere in genome, so no big deal.

Note: Just because Gina has genes that will normally metabolize these medications, that doesn’t mean that she should take them. So, please don’t mistake this test as being diagnostic for you or your child. This test is just one part of the puzzle.

Similarly, even though many medications are listed in the third column of my results, that doesn’t necessarily mean that those medications won’t be effective for me.

Next post:

We explain the basics of genotyping, so we can start helping you how to make sense of and use genotyping data

Meanwhile, we welcome your comments.

For links to the entire series:

1 (this post) of this series provides an overview to the topic.

Part 2 (this post) shares testing results for my husband and I, along with my husband’s reactions.

3 dives into the details of genotyping: what does the term mean?

4 examines “when and why” to pursue genotyping, the real-world value and usage

5 covers the limits of genotyping

6 brings it all together with a closer look at our personal testing results and real-life application of the findings, beginning with Gina’s results

7   …and continuing with Dr. Goat’s personal test results.

 

—Dr. Goat and Gina

16 thoughts on “Part 2: Genetic-Testing for Choosing ADHD Medications”

  1. Have you read Thom Hartmann’s new book “Adult ADHD How to Succeed as a Hunter in a Farmer’s World” which ties characteristics of ancient hunter-gatherer society personality needs for success, versus ancient Farmer societies who had different personality characteristics needed for success? I bought and read the book (brief to hold ADHD readers’ attention), and had many “Aha” moments as he described how an adult ADHD person deals with his/her world (both good and bad talents). However, the most fascinating thing was that upon completion of the book, I received the results from my recent DNA testing and, low and behold, I am heavily descended from Hunter-Gatherer societies of Scandinavia, Northern Europe, and Western Asia. While he doesn’t really go so far as to show a DNA connection, in my opinion, IT’S THERE AND HE IS CORRECT!
    I’m wondering if some of these “duplicated DNA’ items you mention are really leftover from our lines being so ancient compared to those of Farmers who arrived later in those areas? I hope more research is done on the topic – it’s fascinating as well as explanatory of our characteristics and uplifting ()most entrepreneurs have ADHD)

    1. Hi P.

      I’m glad you found that theory interesting.

      Just wondering how you know your DNA indicates you’re “heavily descended” from Hunter-Gatherer societies of Scandinavia, etc. To my knowledge, we don’t have that kind of data.

      As to your question:

      I’m wondering if some of these “duplicated DNA’ items you mention are really leftover from our lines being so ancient compared to those of Farmers who arrived later in those areas?

      I don’t recall mentioning “duplicated DNA.” Can you please clarify?

      I don’t mean to rain on your parade, but there is no “our lines” for people with ADHD. The genes thus far identified as associated with ADHD are genes distributed in the human genome. In other words, these are human traits.

      As a side note: The more I learn about homo sapiens, the more I like Neanderthals, which have largely gotten a bad rap. Turns out, some of the most intensely concentrated Neanderthal DNA is found in my homeland: The Tuscany region of Italy. 🙂

      It will be interesting to continue learning about what our genes say about us!

      Thanks for your comment,
      g

  2. I’ve been traveling, and just catching up on the series today.

    There are so many complexities that come into both diagnosis and medication applicability for any one individual, beyond the snps – copy variations, gene expression, methylation, myelination, nutritional status, hormonal status, microbiome status, toxic load, family & community culture…the list goes on and on! That said, knowing certain genetic truths can be invaluable in planning and assessing a med trial – for example, if one is an ultra-rapid 2d6 metabolizer…

    And I agree with you Gina, a true deep understanding of epigenetics is where the rubber will meet the road…eventually!

    To that point, I’m particularly interested in what you as a geneticist, Dr Goat, thinks about the differential susceptibility (aka orchid/dandelion) hypothesis? Some of these proposed uber-plastic genes are the very ones indicated in both psycho-behavioral problems (including adhd) AND exceptionally positive outcomes, under the ‘right’ environmental circumstance. Sooo fascinating!

    Thrilled the two of you are doing this and that 23andme may be next on your hit parade!

    1. Hi Lattegirl,

      The complexity is overwhelming! I spend hours editing these posts, in order to make them understandable to the lay public, but also accurate. It’s a challenge.

      I’ll forward your question to Dr. Goat.

      Meanwhile, one prominent researcher doing interesting work vis a vis ADHD and genes is Stephen Faraone. e.g. http://www.ncbi.nlm.nih.gov/pubmed/15950004

      Thanks for your comment,
      g

  3. I’m so glad you’re covering this topic in depth! It’s fascinating and (hopefully) practical.

    I have a question, though. The article states, we know ADHD is heavily genetic. But has that truly been established? I understand it’s highly heritable, but I didn’t think we had fully pinned that heritability on genetics. Can you point me to a study supporting your statement?

    I ask because I just read this evening (in The Brain Maker) that babies born via cesarian section are 3 times as likely to be diagnosed with ADHD. That seems to be pretty strong evidence that genetics is only part of the cause (and perhaps even a very small part?), and that environment may play a substantial role in the phenotypic expression of ADHD.

    Of course, that’s all tangential to your article here: As long as medication remains an important part of my ADHD treatment, I’ll gladly accept the help of pharmacogenomics in finding the best medication. Thanks!

    1. Hi Douglas,

      Thanks so much for your enthusiastic response. We had no idea how this series would be received.

      My sister wrote, after the first post, to say, “Don’t you think that’s too….technical?” 🙂

      As for your question, when we say “heritable,” it means that we’ve determined the fraction of the condition/trait that is due to genes.

      “It is now well established that the biological relatives of children with attention deficit hyperactivity disorder
      (ADHD) are at increased risk for ADHD and other psychiatric conditions. Additional lines of evidence
      from twin, adoption, and segregation analysis studies suggest that the familial aggregation of ADHD has a
      substantial genetic component.”

      That’s from an early study by a leading research, Stephen Faraone, PhD, in 1999. http://www.ncbi.nlm.nih.gov/pubmed/10327912

      There are more. I will find them when I have time later.

      Now, not all people who have ADHD come by it genetically. There is a fraction with ADHD due to head trauma, chemo, and the like.

      In the case of Caesarian, there could be other causes for the higher rates of ADHD (if indeed it is true ADHD and not a condition that is mimicking it). For example, some birthing experts contend that the journey the baby makes through the birth canal, with the squeezing of the skull, stimulates the brain in certain ways, promoting its development.

      Also, it could be that whatever condition the mother has that leads to the Caesarean instead of natural birth could incline the child toward ADHD. There might, in fact, even be higher rates of ADHD among mothers having a Caesarean. I would not be surprised by that at all. I’ve collected more than a few anecdotal reports of women with ADHD having very long deliveries, which finally necessitated a Caesarean. Perhaps the “dopmaine signalling” is not happening in a way that fosters natural birth.

      Lots of factors here.

      Overall, I’m clamoring for more attention to epigenetics. Americans, in particular, are deficient in a wide array of key minerals, vitamins, and other nutrients. Nutrients that should be in the mother at the moment of conception, because the nervous system is the first to develop. We really don’t know what is causing the “ADHD genes” (which are present throughout the human genome but when clustered in number or strength present as ADHD) to express or the countervailing genes not to express.

      Thanks for your question!

      g

  4. Hi.. my ADHD is so bad that as a middle-aged woman i really do have trouble concentrating, and hence i can only read a fraction of your articles.
    I’m not on any ADHD meds, but i’ve tried Strattera, Ritalin and one of the Amphetamines and i couldn’t hack it.
    I’m just wondering what the test is called and if you happen to know if it’s available in Australia?
    I would ask my GP, but i fear i’d be wasting my time as last time i went to him to enquire about a ‘serious’ Lithium claim that i’d read about he knew nothing about it, (i take Lithium for Bipolar)
    Thank you.

    1. HI there,

      You know, I’m unfamiliar with the genetic-testing possibilities in Australia. Sorry. But I did find this center. Maybe you could poke around the website or contact someone there: http://www.genetics.edu.au/Genetics-Services/genetic-testing-services

      You could ask if there are tests available for these four genes known to be associated with ADHD medication-response:

      CYP2B6
      CYP2D6
      ADRA2A
      COMT

      Even before seeking testing, there is probably more you could do with the standard medications for ADHD.

      Too many times, the medications are not given a fair trial. They are given at too high a dose, for example, or too low a dose. They are not addressing the co-existing conditions. And so forth.

      Also, there are nutritional deficiencies that can prevent the medication from working as well as it could. So, if you’re not already taking a good multivitamin/mineral, you might want to look into it.

      Good luck!
      g

  5. Hi Kidlet — Sure, more data is always helpful. It just depends on your budget and the time you have to pursue it.

    I’m still puzzling how ADHD is not covered by your insurance. I thought that parity meant that psychiatric conditions were covered the same as the rest of the physical conditions.

    I’d check into that.

    g

  6. Penny Williams

    I’m very anxious to read the next part, what this all means really. As I commented on part 1, my son has had many severe reactions to psych medications. However, every single one he had a bad reaction to was in the Green on Harmony X and on the 2nd we tried (which covered even more psych meds). I felt like these tests were useless, but I’m glad to see there’s real data to work with for some.

    I’m hoping you’ll talk about MTHFR and some of those complicated processes that this test considers. My son had a neurogenomic profile a few years ago and was heterozygos on every single neuro-gene tested. That science is very hard to understand for us everyday folk though. 😉

    Penny Williams
    Author of “What to Expect When You’re Not Expecting ADHD” and “Boy Without Instructions: Surviving the Learning Curve of Parenting a Child with ADHD”
    ParentingADHDChildren.com

    1. Hi Penny,

      I wrote a lengthy response to your last comment to that effect. Did you read it?

      This test is not diagnostic. And there are many other factors affecting medication response.

      g

  7. Thanks for the clarifications, Kidlet. Our purposes weren’t to focus solely on Harmonyx but the entire applicability of pharmacogenomics to ADHD. I will add a clarification, though, since it sounds like many people won’t have access to its test. There are other tests, too. We could not possibly check all of them, though; too many.

    It’s hard for me to say if the test will be useful to you. Much is in the interpretation. Since you are working with a clinic that seems to take prescribing seriously, you might wait on the testing until you hit any roadblocks.

    As you’ll learn in future posts, my husband actually takes one of the medications in the third column, to good effect. So, it’s not a reason to rule them out.

    g

  8. Thanks for writing about this and for letting us take a peek at your genes! Can’t wait for the rest of the posts.

  9. Thank you for explaining that. I’d seen these posted in the group, but didn’t really understand what it was about. Love the chimp picture. 🙂

    1. Hi Penny,

      It’s complicated stuff! To make it simple, we broke it into six posts. 🙂

      g

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