Let’s take a closer look at Gina’s results—from genetic tests claimed to guide ADHD medication decisions.
This 7-part series began with a single post in mind. Hey, we said, let’s get gene-tested for ADHD medications-response! We can share the results with ADHD Roller Coaster readers! That’s right: Nerds!
Who is we? Gina Pera, and my husband, Dr. Goat, a molecular biologist and geneticist diagnosed with ADHD at age 37.
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?
The answer is, “Not many.” Is it important? Well, it can be, if you’re having trouble identifying an ADHD medication that helps mitigate your ADHD symptoms. I also think it’s interesting—and it underscores the complexity of ADHD and the medications used to treat it.
To perform a public service, we provide you with a foundation for understanding the these tests’ potential benefits and limitations. There won’t be a test. You might just find it interesting to skim. But we worked to make it understandable to the average person.
Dr. Goat and I appreciate the enthusiastic response thus far. So far, one reader reports reading to the end. Kudos to her. She now knows more than 95% of physicians ordering this test! Just kidding. (Or am I?)
—Gina Pera
A Closer Look at Gina’s ADHD Genetic Test Results
By Dr. Goat
In our previous post, Dr. Goat shared his reactions to receiving the test results—his and Gina’s. We did the testing via a now-defunct company called Harmonyx. (There are other testing options, including some covered by insurance.)
By the way, Gina took the test solely out of intellectual curiosity. She does not have ADHD.
Now that we understand a little more about how these tests work, we dig deeper into Gina’s results. (Already shared in in Part 2: Genetic Testing for Choosing ADHD Medications.) Next week, we’ll revisit Dr. Goat’s results.
The report shows no obvious genetic problems with Gina’s ability to utilize all the medications in the green column (“Try these first”). Does that mean she needs these medications? No. Or that she will derive a benefit from them? No, it absolutely does not. This test is for people already diagnosed with ADHD. The test itself does not make the diagnosis.
Gina- 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. That is, 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 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 post 5 covers 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.
Gina’s ADHD Gene-Test Says:
Here’s the hard-to-see “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.”
The medications in the green “go” column are: amphetamine salts (Adderall), atomoxetine (Strattera), buroprion (Wellbutrin), Clonidine (Catapres), Dexmethylphenidate (Focalin), Dextroamphetamine (Dexedrine), Guanfacine (Tenex, Intuniv), Lisdexamfetamine (Vyvanse), methylphenidate (Ritalin, Concerta, etc.).
Remember:
- Gina does not have ADHD.
- If she were to take any of these medications, it likely would not end well. Despite the “green”.
- This testing does not tell us that a person has ADHD.
- It tests only for genetic issues that might interfere with getting a positive effect from medications — as legitimate treatment for ADHD!
Beyond the side effects she might get from taking a medication for a condition she does not have, do Gina’s selected genes tell us about 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 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 (if we make the image bigger/more legible, Google will penalize this post, so we’ll state it here):
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! Gina has reduced function in one allele. (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”.
As we explained in post 4, “extensive” is the common class of metabolizer. It represents the type of people for which most drugs are designed: “normal” or “extensive” metabolizers. For a refresher, see diagram below.
That’s good. 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. That’s 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 or other medical professional who can 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.
All 7 Posts in this Series:
1. Explains genetic testing as it relates to ADHD medication-response
Genetic Testing for ADHD Medications: Overview
2. Dr. Goat and I share our ADHD genetic test results—and reactions
Gina & Dr. Goat Share Our ADHD Genetic Test Results
3. Defining the term genotyping, or genetic, test.
What Is Genetic Testing for ADHD Medications?
4. Explains how, when, and why this data might prove helpful
ADHD Medications Pharmacokinetics & Pharmacodynamics
5. Reminds that genotyping data provides only one piece of the puzzle.
ADHD Medication Gene-Testing Benefits and Limitations
6. This post – A closer look at Gina’s ADHD genetic testing results
7. Drilling down into Dr. Goat’s Results — to explain more about the data
Dr. Goat’s ADHD Genetic Test Results—A Closer Look
We welcome your comments.
I had a genomind test done in 2016 and my dr ended up increasing my adderall dose to 180mg daily because she said the results said I only receive 1/3 of the medicine taken. I was at 90 mg at time of testing. I commented on prior blog about current situation as I’m off adderall now and cannot get off the couch basically for 6 months. I’m wondering how she came to that conclusion since when I read through test I don’t interpret it saying that I’m ultra rapid metabolizer of Adderall but I could be wrong. Is there anyone who can look at my test and verify my results. My brain is forever damaged because I figured well genetics don’t lie.
Hi again, Sleepy,
Now, hold on a minute! I’m not sensing (from what you write and how you write it) that your “brain is forever damaged.”
Think about getting back into ADHD treatment, conservatively, and see how it is goes…… with all the caveats I mentioned (getting sufficient sleep, eating well, vitamins/minerals, etc.).
You could send me the PDF and I’ll see if my husband can make sense of it. No promises!
Meanwhile, it is SHOCKING how many MDs believe they can interpret these “gene tests” without a thorough education in genetics. Which MDs seldom have. And, if they do, it’s because they work at a high level or in research, etc..
g
Gina, thank you for this immensely helpful series. I’m not sure if you’re still monitoring these comments, but you and Dr. Goat seem to be precisely the experts I’ve been looking for.
I had Genesight testing in 2017 after a miserable withdrawal from duloxetine. I was diagnosed with ADHD in November 2021 and have been having a ton of trouble finding a good medication fit, and I suspect the issue is a combination of 1) being a CYP2D6 ultrarapid metabolizer and 2) having had gastric bypass and thus having limited medication absorption overall, particularly extended release medications. For both antidepressants and ADHD medications, I had very little in my Genesight “green” columns. I found a good antidepressant fit in Pristiq, but my problem with stimulants is that everything lasts far less time than it should regardless of dose, and I experience a significant “cliff” effect when it wears off. IR methylphenidate lasted approximately 45 minutes. IR Adderall, about 2 hours. I was eventually dosing Vyvanse twice a day, with each dose lasting ~4 hours, but eventually discontinued this because of the panic, anxiety, and “hitting a wall” effect when each dose wore off. On my Genesight test, all stimulants have the footnote “COMT genotype is associated with reduced therapeutic response to this drug.” Amphetamines have the additional footnote “Serum level may be too low, higher doses may be required.” My provider got to the point of telling me I just need to adjust my expectations for what I’ll get out of medication, and I’m just now establishing with a new provider.
My questions are: 1) Is there any hope for finding a medication that works for an acceptable duration without awful withdrawal effects when it wears off? I’m considering asking about the Daytrana patch. 2) I know some medications, like Wellbutrin, and some supplements, like Goldenseal, inhibit CYP2D6. Is there any precedent for CYP2D6 ultrarapid metabolizers taking medications or supplements to inhibit this enzyme and slow the metabolism of other drugs?
Thank you so much for reading if you happen to get to this! Of note, I also imported my Ancestry DNA data into SelfDecode and am definitely getting in over my head with some things, like how my A/A COMT genotype is apparently risky (also mentioned on my Genesight test) or how my C/T allele on SNP rs6869645 of gene SLC6A3 had a link to this article: Polymorphisms in dopamine transporter (SLC6A3) are associated with stimulant effects of D-amphetamine: an exploratory pharmacogenetic study using healthy volunteers.
Hi Erica,
I’m glad you found the series helpful! Complicated stuff, we humans, eh?
Yes, when I read “gastric bypass,” my first thought was…Daytrana. I don’t know what’s happening with it now. There were changes in ownership, problems with the adhesive (tends to give a rash eventually, and that seems a common problem with all kinds of Rx delivered via patch).
But if I were you, I’d definitely try to get my hands on those patches.
I have a feeling that’s more of an issue than the mutations, but I really have no idea. This is way above my pay grade. My husband, unfortunately, is deeply embroiled in a work project and family illness. Otherwise, I’d ask him to take a stab.
I’ll send an e-mail with another suggestion.
g
Where is post 7? It would be helpful for these articles to be dated so there is a sense of how old the information is as well.
My son who is almost 17 was recently diagnosed with ADHD. This series has been very helpful as we are just beginning the medication whack a mole journey. I am going to have him tested and hopefully it can be a useful tool to inform the process.
Hi Gigi,
If you look by category, you’ll see all of the posts in the series.
Genetic Testing for ADHD Medications
The information is current and unlikely to change any time soon. Though I cannot keep up with which companies are doing what, the basic information is “evergreen.”
Before you go into genetic testing (which if you read the series, we are CAUTIONING about mis-using), maybe learn about the basic approach to medication that very few prescribers follow.
I wrote about it in my first book: Is It You, Me, or Adult A.D.D.? https://amzn.to/3oNiRz6
As far as the date, I’m working on finding a way to show the date without crowding the intro with type. Otherwise, you can always look at the first comment to see the date.
Generally, though, I try to keep posts current, as much as possible. When they are outdated, I add a note at the top pointing to newer information.
Google Search requires being very careful about deleting old posts.
Thanks,
Gina
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.
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
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!
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
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.
Hi Rhonda,
Kudos to your psychiatrist! Check out my post on ADHD and obesity: ADHD & Obesity: Reviewing the Research
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.
See this paper: Atomoxetine Therapy and CYP2D6 Genotype
In other words, a stimulant such as Ritalin, Vyvanse, or Concerta might be the best bet for you.
Good luck!
g
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
Thanks
I am still interested in the test.
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
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