Part 3: Genetic Tests for Choosing ADHD Medications

ADHD, DNA, and Predicting Medication Response

Welcome to Part 3: Genetic Testing for ADHD Medications.  It is the first online collaboration between my husband (“Dr. Goat”) and me (Gina Pera), and we are thrilled by the enthusiastic response!

To recap:

Part 1 of this series provides an overview of the topic.

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

Before we get to Part 3, below, let me emphasize a caution:

These genotyping tests are only one piece of a complicated puzzle. Please do not assume that your test results are the only factor guiding your or your loved one’s medication choices. That is far from the truth.

Genetic Testing for ADHD Medications—3

“My Daughter Cannot Take Stimulants”

I just encountered one mother who said that her daughter “cannot take stimulants, according to genetic testing.” As a result, the girl was taking only Strattera, at a “maxed-out dose,” and not experiencing a significant decrease in ADHD symptoms.

From her mother’s report, the seven-year-old girl sounded lost in the fog. She was unable to follow the teacher’s communication or even play games with the other children in school.  The mother, therefore, was looking into alternative education. She didn’t want to hear from me that she might be misunderstanding the test results. After all, I’m not a physician.

I worry for that child—and all the people whose physicians are getting it wrong.  That’s why I recruited my husband, who has a doctorate in molecular biology. He has taught medical students. He has worked for many years in genomics. And he has ADHD. Boom.

In the meantime, I’m including a short glossary of technical terms, at the end of each post. To help you keep your bearings. And, you’ll also find a very cool video: The Animated Gene.

Genetic Testing: What Does It Mean?

By Dr. Goat

Dr.-Goat-squareIn recent years, biomedical research has identified many genes that wield a substantial impact on how people react to medications. We now understand many of these so-called “drug-response genes.”

Several companies are making consumer-level tests available. Their purpose? Revealing the kind of drug-response genes the consumer might have. Some of these tests require a doctor’s prescription. Others offer workarounds, in case your own prescribing physician is unfamiliar with the testing. Costs vary.

The point of this blog series: to examine how these tests, in general, might prove useful—or not.

Though far from perfect, these tests can now provide valuable insights into what drugs, at what dosage, might be best for treating your or your loved one’s ADHD— and which drugs might pose complications.

This post establishes a foundation for understanding these genetic influences. Subsequent posts will examine one particular test (Harmonyx) in the context of my particular results (Gina’s, too!). We’ll also cover general interpretations of how one’s test results might influence treatment. The rest is up to you and your physician.

[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.]

You won’t come away from this series of posts knowing everything about genes and drug-response. But you will gain a good general understanding to benefit your or your loved one’s ongoing healthcare treatment. Best of all, you will be better able to participate in treatment decisions.

Genetic Testing for ADHD Medications—3

Hey Genes, What’s Your Type?

We refer to these genetic tests as performing genotyping, so they’re called genotype tests.

First, let’s examine the term genotyping. Your genotype is your particular genetic makeup. So, when we talk about genotyping an individual, we simply mean performing tests that identify what kinds of genes are present in that person’s cells.

Of course, all humans have the same basic genes, but each particular gene comes in a particular “variant.” (Technically, it’s an allele. But because I’m writing for a lay audience, not a scientific one, let’s keep it simple).

Genotyping is one component “personalized medicine” trend. That is, where health assessments and treatments keep the individual in mind, instead of what has been shown to work in large groups of people.

types of vehicles

Genes….And Consequences

Some gene variants are associated with different functional consequences. What is a functional consequence? Consider the following analogy.

Most adults drive a variant of four-wheeled vehicles. Some drive a truck powered by a robust engine that makes it possible to haul big loads—though at the cost of low gas mileage. Others drive a car with a weaker engine that provides the owner with excellent gas mileage—though at the cost of power.

The same is true of genes: one variant of a gene is associated with certain properties; other forms of the gene have other properties.

This is what genotyping does: it tells you whether your vehicle (that is, a particular gene) is a truck, a fast car, a gas-efficient car or, let’s face it, a clunker. Genotyping tests can do it for one gene or many genes.

Genes, Meet Medication; Medication, Meet Genes

There are two main aspects of pharmacogenomics—the study of understanding genetic influences (genomics) when it comes to medication (pharmaco):

1. Pharmacokinetics: “What the body does to the medication”

Many genes are known to affect how the body metabolizes a drug—in other words, how the body processes and ultimately discards the medication. For example, some genes affect the rate at which the body removes a drug from the blood.

Pharmacokinetics seeks to tell us about what happens to the drug, beginning when it enters the body and ending when it is completely eliminated from the body.

2. Pharmacodynamics: “What the medication does to the body”

Other genes influence the mechanism of how drugs affect cell function. Pharmacodynamics seeks to tell us about the mechanisms of drug action—how it affects the body—and the relationship between drug concentration and effect. In short, it tells us how the drug works.

All drugs have specific mechanisms of desirable action as well as various adverse effects that are caused by pharmacological interactions in the body.

 

pharmacokinetics and ADHD

Depending on your genetic variants, your particular response to a medication may be weaker or stronger than another person’s.

Keeping with the vehicle analogy, you may have to stomp harder on the accelerator of a car with low horsepower than you would with a higher-horsepowered car, to reach the same speed.

Translated: You might need a higher or lower dose of medication to get the same beneficial effect, depending on the individual.

This, in a nutshell, is what we mean by Personalized Medicine.

We’ll explore both aspects of pharmacogenomics (pharmacokinetics and pharmacodynamics) further in the next post.

Genetic Testing for ADHD Medications—3

Visit The Animated Genome Page!

Meanwhile, check out this beautifully done video below, from the Smithsonian National Museum of Natural History and the National Human Genome Research Institute: “The Animated Gene.” (Click on the image to go to the site.)

THE ANIMATED GENOME
CLICK TO VISIT “THE ANIMATED GENOME” PAGE

 

How about you?  Have you tried any of these genotyping tests, for ADHD medications or for other purposes? Did your physician initiate the testing and interpret for you?  Was the information helpful?

Next post: Part 4: Why and When to Pursue Genotyping

To recap:

Part 1 of this series provides an overview of the topic.

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

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

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

Part 5 covers the limits of genotyping

Part 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

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

16 thoughts on “Part 3: Genetic Tests for Choosing ADHD Medications”

  1. It is very important to prescribe dose of ADHD according to age, medical history, and symptoms. Children are very sensitive to ADHD medication. It can be one version suits and the other does not.

    There are many ADHD variants ranging from Adderall to Concerta to Vyanase. Being a concerned aunt, I wanted my niece to get the best version.

    She is hyper and intelligent at the same time and shows signs of irritability and finds her peace in art. Controlling her or keeping her entertained for longer periods of time was a problem.

    The GP does mention about Adderall because it differs from other drugs but how the child responds to it is totally up to the genetic makeup. Dosage is a key factor in keeping “age” and “tolerance” to the drug.

    If the child is taking some other medication then contraindication must be checked too.

    For kids, combinations of CBT and group therapy needs to be added.

    1. Hi Elena,

      Thanks for your comments. All great points. My first book details a methodical approach to medication.

      One thing that’s interesting. Sometimes children will need a higher dosage than adults (all things being equal). The reason is children metabolize the medications faster.

      What a wonderful and involved aunt you are!

      G

  2. I want to thank you and your husband so very much for this series, and for your passion for helping people cope with ADHD. It’s interesting how things play out (e.g. issues related to this statement from Harmonyx http://www.harmonyxdiagnostics.com/ ) and I was wondering if you and your husband had thoughts on this situation when it comes to how the system can work to best help those with ADHD and other neurodevelopmental and psychiatric conditions.

    May I also ask if it is your understanding that Genesight is the currently the only company offering this sort of testing service in the U.S. ?

    I have one more question, and I’m sorry for asking all of this. We are just trying to make the best decision we can, and we really appreciate the work you have done in this area. If reasonable at this point, would you and your husband be willing to expand a little on one of your comments (below, and thank you for leaving comments!) on this Atlantic article? If you’ve continued to follow the company, do you think Genesight has made progress in the area of your concern?https://www.theatlantic.com/health/archive/2015/05/a-test-that-finds-the-perfect-drug/393611/

    You said, “I’m speaking particularly of [Genesight] ADHD meds genotyping. Such a test needs to be based on evidence, that those genetic variants are indeed associated with what the test claims. My husband examined their test and found that it went a little far afield. Not horrible, but not entirely solid.”

    Thanks so very much again!

    1. Hi Searching Mom,

      Thank you so much for the kind words. When I started thinking about a blog post to clarify consumers’ confusion on the gene testing, I thought it would be one post.

      But then we got started, and so many terms needed defining.

      The trouble is, many physicians do NOT understand the testing results, and that is causing children and adults to be deprived of the first-line treatment for ADHD, the stimulants. It’s a really horrible situation.

      To answer your question, yes, my understanding is that Genesight is the only company offering this type of testing. For some people, insurance will cover it.

      As for the article, it is from 2015. I’d read closely the comments from Dr. McGough and Dr. Stein, both ADHD experts I highly respect.

      The bottom line for this testing: It can be most useful for people who are slow or rapid metabolizers.

      If slow, that will give extra emphasis to “starting low, titrating slow” (which prescribers should be doing anyone but many, perhaps most, do not).

      If rapid, that will encourage the prescriber to try higher doses of the first-line medications (stimulants) before abandoning that class and trying something else.

      Also, this might be proof for the insurance company that the patient actually does require two doses per day, even of the extended-release products such as Vyvanse and Concerta. (Even many people who are NOT rapid metabolizers will require two doses.)

      We haven’t examined the data on which Genesight is basing its testing, and we are both deeply involved in other projects. I’d say it’s probably accurate enough. But still, we MUST take these results witha grain of salt. Again, reading the last post in the series and remembering the comments from Drs. McGough and Stein.

      I hope this helps!
      g

    1. HI Esra,

      I’ve not seen a way to use 23&me data to inform ADHD medication choice.

      There are some sites that will interpret the data for specific issues. One that I know is http://www.geneticgenie.org. There’s a “detox profile” and a “MTHFR” analysis. The latter can be particularly helpful.

      Other than that, I think that the company GeneSight is the only one offering the ADHD-Rx testing. It’s often covered by insurance, but otherwise is fairly expensive.

      The thing is, you don’t need any genetic testing to figure out which medication to try. Use the basic protocol detailed in my book. It’s the tried and true, common-sense method. http://amzn.to/2kML1cD

      If you are sure to “start low and titrate slow”, you will best avoid any problems if you are a slow metabolizer (these are the folks who do best on lower doses). And, if you keep gradually increasing the dose (titrating) until side effects outweigh benefits, you might deduce that you are a rapid metabolizer (people who need extra-high dosages).

      Here is a summary of all the posts in this blog series: https://adhdrollercoaster.org/tools-and-strategies/post-7-gene-testing-to-inform-adhd-drug-therapy/

      good luck!
      g

  3. Hi Dr. Klein,

    Thank you so much! I’m glad you enjoyed the series.

    My husband and I plan to make a narrated video based upon it. I think that will be easier to understand for some folks.

    But yes, we should probably create an e-book from it, too. Thanks!

    g

  4. I am so enjoying this series! I also want to say “Thanks” in advance to your consideration of those, moi included, who get a lot more out of pictures in motion! Saves me the real time mental conversion!

    1. Thanks so much, Dennis! Your comment makes me feel like it was worth it to spend EIGHT HOURS editing it yesterday. 🙂

      That’s after working with Dr. Goat to write and edit the entire series!

      Definitely, we’ll work on the Major Motion Picture. 🙂

      tx
      g

  5. I too wish that the 23andme health reports were still available – and I think it’s rather absurd that the FDA has tied their hands in this way!

    The 3rd party sites I’ve been playing around with include: Promethease, Genetic Genie, Yasko, LiveWello, NutraHacker, MTHFRsupport, plus a couple sites that are more focused on ancestry.

    You are doing an awesome service for people here. Thank you!!

    1. Thank! Yes, I checked out Genetic Genie and MTHFRsupport. Didn’t know about the others. Thanks.

      I’m mixed about FDA decision.

      I’m already seeing how parents are making some disastrous decisions about their child’s medical care, from the ADHD and other-related tests.

      There should be a system or specialists for helping people interpret. Especially since so much is speculative.

      g

  6. Penny Williams

    Your analogy to different vehicles is inspired! And, it can be used to explain other things, like ADHD! I’m going to keep that one in my back pocket. 😉

    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

  7. I did the old 23andMe test a few years ago. It didn’t include drug responses to any stimulants, but it mention that might have an exaggerated response to Warfarin, for example, and should be careful with dosing. If I ever require anticoagulation therapy, I’m in the know!

    I also found out, for example, that I have a higher chance of developing rheumatoid arthritis (which I can’t do much about, but is interesting to note), and I’m also in a higher risk group for breast cancer. Now that is where this kind of test is potentially life-saving! Because of that, I am much more thorough in self-exams than I might have otherwise been!!

    I’d love to do another test if the technology is improved. It’s amazing what they can tell you!

    Great post series. It’s very educational. 🙂 I love it. I’m going to send this along to my mother, actually. She’s a former biology and genetics teacher with ADHD. She’ll eat it up!

    1. Hi Carolyn,

      Thanks so much for your comment. I am glad you are enjoying the series, and I hope your mom does, too.

      You know, the 23andMe test probably did/does include genetic information relevant to ADHD medications (and others), but it’s so hard to decipher it. Especially now that you can only download the information as a data file. I’m looking into other avenues and will posting about that in the future.

      I understand the FDA wanting to make it clear to consumers that such information is not deterministic, because many people think about genes in those terms. Still, I wish more MDs were astute at making sense of the important factors. There is so much more we could be doing to improve people’s health, including mental health.

      For example, it might be that you can do something about the higher risk of RA, epigenetically speaking. I’m not sure what, but I bet there’s something. You know the old saying….”Genes load the gun, but environment pulls the trigger.”

      Thanks for visiting,
      g

  8. The Masked ADDer

    Great job, Gina! Not easy explaining this stuff, yet it is important for patients to understand it when considering medication.

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