Genetic Testing for ADHD Medication Series—Part 7

ADHD Gene Testing

Welcome to the final post in this series on genetic testing for ADHD Medication. 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:

  1. Didn’t require a physician to order it
  2. Reasonably priced at less than $100, and
  3. 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. The overriding message is: Be careful about physicians misinterpreting these results. Your or your child’s appropriate treatment relies upon being a smart consumer.

ADHD Gene Testing Series in Seven Parts: 

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 my results.

Highlighting Our Test Results: Dr. Goat’s

By Dr. Goat

ADHD Gene TestingAs I wrote in my previous post:

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. To read the larger version, click on the image below.

ADHD Gene Testing results

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 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 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.

Guidance Notes

Here are the guidance notes for this particular “menu” (to view a larger version, click the image):

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

Genotype: CC

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).

 

ADRA2A Gene

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!)

ADHD Gene Testing

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.

Genetic Testing for ADHD Medication

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.

Translation:

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

Genotype: *1/*6

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.  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.

 

—Gina Pera

42 thoughts on “Genetic Testing for ADHD Medication Series—Part 7”

  1. Gina,

    I am so disappointed to learn that Genesight doesn’t test for response to the ADHD medications. Do you know of any other companies right now that do???

    1. Hi Laura,

      Why are you disappointed? What were you hoping to learn?

      There is really not much benefit — and if not read correctly, results can lead treatment astray.

      That’s why we wrote a 7-part series. To warn about this.

      g

  2. Thank you for covering this info. As I’m sure you know, Harmonyx is not currently active. My child was genetically tested as a rapid metabolizer CYP2C19.
    He also has ADHD.
    Do you have any info on what his try first / next / last meds would have been?
    His dr was willing to apply this information but admitted to being ignorant about what to do with it. Thank you.

    1. Hi Melanie,

      Yes, unfortunately Harmonyx is no longer administering this test. For various reasons.

      The three columns of first/next/last medications were a problem from the beginning. After hearing reports from parents, misinformed by the notion that they could not give their child medications in the first column, I tried to educate the public on what this testing truly meant. And it wasn’t that.

      The main benefit of this testing, for most people with ADHD, is to identify whether one is a rapid or slow metabolizer. Now that you know your son is a rapid metabolizer, that means that he might need higher-than average dosages in order to have the necessary effect.

      Otherwise, your son’s prescribing physician should be following a standard protocol for treating ADHD plus any co-existing conditions.

      I hope this helps.
      Gina

  3. Is there a site that gives all the types of codes for ADHD? I had some done but can’t read what the results mean. I understood the C/C example because I am the same. My therapy office is trying to use this to say that you are or are not ADHD. Any suggestions would be helpful. Maybe a chart of some kind.

    1. Hi Alyson,

      I’m not sure what you mean — “all the types of codes for ADHD.”

      Do you mean genetic markers? If so, there are none.

      These genetic tests examine factors that affect medication.

      I’m not sure what your therapy office is aiming for, but there is NO genetic test for ADHD.

      best,
      g

  4. Ι constantly spent my half an hour to read this web site’s articles
    or reviews aⅼl the time along with a cup of coffee.

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

  6. Gina,
    Thank you and your husband for providing this much needed venue for those with and impacted by ADHD. I appreciate the scientific detailed and current information presented in a professional manner. Keep up the great work! Lyn

  7. Thank you so much for posting this! My 8 year old is adhd and trying to navigate all the info out there is overwhelming. I think we will have to really consider trying this for our son.

  8. Margaret Shibley

    It would be nice to know whether the gene testing is available in Canada. (It would also be nice to know if “Margaret”s are statistically overrepresented in this responder list. I wonder if it might also indicate an age group? 😉 )

    The experimental phase of finding the right drug is exasperating – it takes an expert advisor, it takes time, it takes a close observer to verify and sometimes notice results – all at a time when life continues at the speed of light! My 22 year old will have none of this medication stuff – we never did find what worked for him. His brother, at 17, has just been diagnosed, and after a catastrophic Concerta-induced breakdown in school, is also heavily resistant. He is virtually paralysed by stress when it comes to school work and exams. He needs some help NOW. The other lad hasn’t face the same ‘failure to launch’ issues – he’s launched in so many directions over the past 4 years that you can spot our house on the horizon because of the fireworks! My own diagnosis didn’t come until after menopause decimated my already inadequate coping skills. Continuous chaos is not a comfortable way to live. It would be huge if this testing could shorten the route to help.

    I have to say I really appreciate that you take the time, and provide readers with the courtesy of respect, to provide the scientific details with no apology. There is so much pseudoscience out there, that I really appreciate being able to get at the results from the beginning, instead of hearing summaries of summaries of summaries.

    1. Hi Margaret,

      Summaries of summaries of summaries! Perfect! That’s how I felt about book’s descriptions of ADHD medications. A summary ending with “talk to your doctor.” But what if the doctor knows diddly?

      That’s why I included several chapters in my book.

      And thank you for noticing that I like to treat my readers with respect. It was a gamble, getting this “geeky.” But I figured at least a few people would appreciate it. Instead, it’s been extremely popular (though you wouldn’t know it by the paucity of comments on the rest of the posts).

      I have asked my contact at Harmonyx about Canada. Will report when I learn.

      tx
      g

  9. I am learning so much from this. Thank you once again for all your hard work. Your opening so many doors for people like myself.

    Now on to my situation. I have already told you that I’m talking Concerta 36mg 2 X daily.

    The thing is it does work, however years before I was diagnosed with ADD I was on medication for weight loss and that medication was the perfect fit for my ADD. It was however a drug that was taken off the market due to abuse years ago by people who didn’t need the drug. As for myself it worked wonders for me. Far better then the Concerta I am now taking. The problem is with so many people abusing drugs these days It’s hard to walk into a doctors office and say I want to take stimulants because they worked so well in the past. And I realize Concerta is a stimulant. The Concerta does work but not nearly as good as the drug I took years ago. For that reason I would really love to get this testing done. Seems like the whole world is more concerned with the drug abuser’s then the people who truly benefit from this type of medication, myself being one of them. The Concerta is not without side effects and as I said it does work but the feeling of well being isn’t the same as it was on other medications. I have settled for the drug I am now taking because without it I would be unable to stay awake, or drive a car, or hold down my part time job that requires a lot of paper work. My life is at least livable taking Concerta but how I long for the right drug to help me live the productive life style of my past. It’s really hard knowing how much better I can feel on the right drug but still be stuck on a drug because no one really knows which drug is the right drug to prescribe. ( Sorry for all that double talk) LOl

    1. Hi Margaret,

      Thanks for your comment.

      I’m wondering if you ever tried Vyvanse, Adderall, or Dexedrine. It might be that you are one of the people who responds better to the AMP class (Amphetamine) than the MPH (methylphenidate) class.

      MPH – Ritalin, Concerta, Daytrana, etc.
      AMP – Vyvanse, Adderall, Dexedrine.

      I can imagine how frustrating that must be, remembering how much better another Rx worked for you. It might be like remembering how skinny and agile I used to be. lol!

      Maybe you could research it and see what was the active ingredient in that drug. (Are you talking about FenPhen?)

      Thanks for your comment,
      g

  10. Knowing which medication doesn’t work well because of a genetic variant will help a lot. I appreciate Dr. Goats experience with medications and thank you both for taking the time to inform us on this complex subject. I am 67 with ADHD, taking stimulant medications with an unpleasant experience with Strattera in my past, and would be open to augmenting my meds to make my wife’s life easier. Everytime I think I have moved toward normal in some way it isn’t long before I am reminded or realize my improvement is a cut off a cartload compared to the work remaining.

    Scott

    1. Hi Scott,

      A “cut off a cartload.” That’s a new one! I like it. Very alliterative. 😉

      I bet the Strattera was at a high dose? My husband takes 40 mg. He cut back to 25 mg one time, and let’s just say, neither of us enjoyed that interlude. 🙂

      Most people (including MDs) would be skeptical that a mere 15 mg could make such a difference. But trust me…

      Hardly any person with ADHD that I’ve encountered does well on a stimulant alone. There almost always needs to be a balancing act with the other neurotransmitters. So, a stimulant with low-dose Concerta or an antidepressant….that’s pretty typical. But there are a ton of exceptions.

      Good luck with that cart!
      g

  11. Thanks so much for this series. We reside in a rural area in No. CA and have been unable to locate where/how we can access a Harmonyx testing kit. Can you please provide more info on this? Thanks

    1. Hi Denise,

      Harmonyx says the kit will be available on the West Coast soon, through Rite-Aid stores. Maybe one is near you?

      If not, there are tests that your MD can order, such as through Genesite. Sometimes insurance pays for part of it.

      Another option would be trying http://www.23andme.com But you get only the raw data, which must be converted into an accessible form. Some websites are starting to do that. So, this would be an option for these ADHD meds only if you pick out the various gene variants from the 23andMe data. Not for everyone.

      best,
      g

    2. Hi,
      Just wanted to add something to Gina’s suggestion re 23andme.

      We’ve done that testing, and while it’s very helpful on many fronts, it tests for selected snps but not copy number variants. So, if we had not also done targeted P450 genetic testing through our doc, we wouldn’t have learned that she was in the tiny percentage of caucasians who are cyp2d6 ultra-rapid metabolizers – thus making some medications/doses potentially too weak (e.g., strattera) and others too potent (e.g., codeine).

      Harmonyx I believe, as well as tests a doc would order, will look at pertinent polymorphisms and copy number variants.

  12. Thanks for the series! My hubby has been experimenting for 10 years now, but is interested in what the DNA might suggest. Very interesting series.

  13. Jodi Breyfogle

    Very informative series of articles. We have been considering this but didn’t know of anyone who actually had the testing done

  14. Margaret Pfeiffer

    Thanks Gina for a great series…my husband Steve is anxious to take the test, but we found the closest pharmacist who offers it in the San Francisco Bay Area is located in Patterson (central valley). Steve talked to our local Walgreens pharmacy, but as mentioned in a post above, they cannot offer it unless it comes down from corporate. Any chance you could advocate at the high levels of CVS or Walgreens to get them to offer this testing in communities that are requesting it? I’m sure we could get a fair number of folks from you ADHD support group here in the Bay Area to take advantage of it.

    Thanks again for all you do for this community.
    Margaret

    1. Hi Margaret,

      I learned this yesterday from Harmonyx. They are partnered with Rite Aid and the roll-out on the west coast will be implemented in the next few weeks.

      g

  15. I read all parts of the series. While some of it was a little technical, I found it very informative. It’s exciting that they have this testing and hopefully it’ll help when trying to figure out where to start.

    My husband and I are both ADHD, not realizing it until adulthood after getting our kids tested. And guess what, both kids are ADHD as well! One is hyperactive and the other, inattentive. I feel as though we have a decent combo for the inattentive child, but we can’t nail down a medication combo for our hyperactive child. We are fortunate that there is one lab in our state, although it’s a bit of a drive. I’ve been going back and forth as to whether or not to get said child tested, as it seems that the testing is more of a guide, than an answer. But, I guess it’d be interesting to see what the results are!

    Thanks again for the thorough and thoughtful post.

  16. Thank you for the interesting series of articles. I am considering getting genetic testing for my son who has ADHD, prior to starting him on any medication. I think it may give his doctor a better idea of what medication to try first, rather than guessing.

  17. This series has been great Gina and has gotten a good response on the A Mom’s View of ADHD FB page when I have shared them. I think riding the medication roller coaster is one of the most frustrating parts of parenting a child with ADHD. We have had really awful experiences with medications for my son. Nobody likes feeling as though your child is a “guinea pig” when you begin trialing medications. Being able to use genetic testing like Harmonyx takes some of the fear and dread and frustration out of the experience. I would love to be able to test my Ninja Boy! I tried to access Harmonyx months ago when it was first made available but no local pharmacy is offering it. I have talked with the pharmacists at the place where I get prescriptions filled and they are interested in offering it but are part of a corporation (grocery store) so of course have to wait for corporate to get on board. I hope many families can begin to take advantage of this opportunity, especially because it is relatively affordable. Thanks again to you and Dr. Goat for this very informative series!

  18. Hey there I am so grateful I found your website, I really found you by error, while I was searching on Aol for something else, Regardless I am here now and would just like to say many thanks for a remarkable post and a all round thrilling blog (I also love the theme/design), I don’t have time to go through it all at the minute but I have saved it and also included your RSS feeds, so when I have time I will be back to read a great deal more, Please do keep up the excellent job.

  19. People Person

    Thank you so much for doing this series – this kind of testing would have been exceedingly helpful to my ADD daughter’s journey!

    I’m also wondering if you know what the next mental health condition/medication areas will be for Harmonyx to pursue, and whether they might also look at some of the well-understood herbals in the future?

    I can’t wait for your future forays into genetic testing and interpretation!

  20. WOW! is all I can say. I’ve been teaching for 16 years and have seen ADHD meds in the classroom setting for a while. Then I had my own two beautiful littles and come to find out my husband and I breed ADHD! He was diagnosed shortly after my 2nd child was born and has struggled to find the right med. Both children are on some type of med, but their ADHD manifests itself differently in each. Me being the only non-diagnosed person in the family is continually trying to make sure that my children are on the right meds, and trying not to nag my husband when I know in my heart that he isn’t on the right medication! The first person in the family to get the testing will be my husband! These posts have been very interesting and informative! Thank you so much for the research and the writing the article in a way that a regular old joe can understand!

  21. Margot Collocott

    Thanks for one’s marvelous posting! I seriously enjoyed reading it, you may be a great author.I will be sure to bookmark your blog and may come back down the road. I want to encourage one to continue your great writing, have a nice holiday weekend!

  22. Fascinating. It does seem like this test could help lessen at least some of the trial and error involved in finding the right medication and the right dosage. I really learned something new here. Thanks!

    I loved the mental image I got of Dr. Goat riding his High Horse.

  23. Denise Mueller

    My son Matt is 22 years young and he’s been inundated with ADHD for several years. He’s tried Concerta and Adderall, plus his doctor even gave him Paroxetine, a generic for Paxil; however, not to much success. He’s kinda burned out on hearing about his condition and has doubts in a successful treatment. I think he would jump at the chance to try the Harmonyx Diagnostic test to know what might be a solution in understanding his make-up and his choices. Thanks for your help with this issue.

    P.S. I loved this series keep up the great work!

    Denise Mueller

  24. Sheila Morris

    Now this stuff gets me excited. I love science for trying to make sense of the seemingly unfathomable.
    Genetic study has always fascinated me, and now that I’m the adoptive mum of a young boy with ADHD my interest in genetics has been fuelled again. I would be thrilled to find out my boy’s genotype, to help in future decision making when it comes to his meds. We are presently involved in the “trial and error” stage, working out amounts and types of meds. It would be a lot easier with some sort of “guide”, such as harmonyx. I’m very interested in this work!!!
    I just recently stumbled upon your blogs, and have been glued to my email for the latest posts!
    Thanks for the insight,
    Sheila

  25. until your blog post I had no idea this was available for ADHD. Thank you so much for this valuable information. My husband is really struggling with his adhd symptoms right now and could really benefit from this testing

  26. Thanks for your posts! I did not even realize such tests existed. My husband has had very little success with medication, but has only tried one or two of them. Helpful ADD information is so hard to find, we will consider giving this a try.

  27. Wow. That is so complicated. No wonder it’s so hard to find medications that work well and explains why a migraine medicine prescribed for a friend, won’t do a thing for me.

    And doctor’s really like that one size fits all idea, don’t they?

    Thanks for explaining all that to us. I really didn’t understand it at all when you posted it to the group.

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