Part 4: Genetic-Testing for the Best ADHD Medication?

Best ADHD medication

Welcome to the next post in my 7-part series: Genetic Testing for Choosing ADHD Medications — Part 4.  This post’s question:  What’s the best ADHD medication? The answer:  The medication that works best for the individual.

Don’t you hate that? Are there any easy answers when it comes to ADHD?  If you’ve found some, drop me a note below because I’d love to hear them.

Trouble is, ADHD affects individuals—not clones. The genetic factors are highly variable. The genetic testing for ADHD medications do not provide the slam-dunk answers many patients and doctors seem to think they do. Without being clear on this, you risk depriving yourself or your loved of your best medication treatment.  Over 7 posts, we explain what you and your prescribers need to know.

But, yes, genetic testing for ADHD medications can provide some useful information. Specifically, you can learn more about how your genes affect how you respond to medications—and how medications respond to you!

This ADHD Genetic Testing Blog Series

My scientist husband (“Dr. Goat”) and  I pooled our neurons to bring you this series. The goal: more accurate information for the layperson (and medical professionals) with little background in molecular biology or genetics.

Our collaboration required much tedious editing and back-and-forth. My twofold goal with all my books and blog posts: accuracy and clarity.

By the way: Ten years ago, no one could have imagined Dr. Goat and me working together so harmoniously on a project. Instead, picture miscommunications galore, chronic conflict, tempers raising the roof, and few epithets tossed around before we both said, “I give up! You’re impossible!”

Thank goodness, we are past those days. Working together is fun and productive. The fact that we can now team up to produce information designed to elevate the lives of our readers? Doubly rewarding.

To Recap Previous Posts:

1  — Provides an overview of the topic of genetic testing for ADHD medications—including the importance of proper interpretation

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 genetic testing (or genotyping)– briefly, it’s a test that informs you of your genetic particulars— specifically for our purposes in this blog series, tests that identify which variants of the drug-response genes known to be associated with ADHD medications that you have

Here in part 4, below, you’ll discover how, when, and why this data might prove helpful.  There is no “best medication” for ADHD. But armed with information about your genetic factors affecting drug response, you can find the best medication for you or your child.

Note: This post is a little longer than the previous ones. We thought it best, however, not to break up the concepts. So, settle back, take it slowly, and enjoy! This is fascinating stuff, with applications that extend beyond ADHD medications.

best adhd medication

—Gina Pera

What’s the Best ADHD Medication? That’s the Wrong Question.

By Dr. Goat

Dr. Goat and Gina PeraGenetic testing for ADHD medications offers one clear benefit: it can help to identify whether you metabolize medications slowly, normally, or very quickly.  That’s what this post in the series is all about.

Now, what is the first very important point to understand about medications? That’s right: Dosing matters. Assuming that the diagnosis is correct and the medications being considered are recommended for it, beneficial effects depend upon identifying the dosage that works best for the individual.

Too low a dose? You don’t get a therapeutic benefit (nothing happens).

Too high? You might start encountering unacceptable side effects—despite that medication being an excellent choice for you.

So, just like Goldilocks, it is crucial to reach a “sweet spot” of dosage. In that sweet spot, you will get the full benefit of the drug with minimal side effects. [Gina does an excellent job of explaining this vis a vis ADHD medications in her first book, Is It You, Me, or Adult A.D.D.?]

Gene Variants Dictate Drug Response

One factor to consider when aiming for that sweet spot of medication effectiveness: how your specific gene variants affect drug response.

We discussed “gene variants”  in post 3.

To recap: Genetic variation (or variants, sometimes called mutations) describe the tiny variations in the DNA sequence in each of our genomes. Genetic variation is what makes us all unique—of hair color, skin color, height, or even the shape of our faces. (Learn more at Genomics 101: What is a variant?)

That’s where genetic tests come in: They identify these gene variants—that is, variations on a common gene. In turn, this information helps you to:

  1. Determine what dosage you should start with, and
  2. Decide the order in which drugs should be evaluated.

This information can be especially valuable if you are

  1. Beginning drug treatment for ADHD,
  2. Considering changing to a different drug, or
  3. Introducing an additional drug to your regimen.

It’s worth re-emphasizing: Genetic testing for ADHD medications will not be a “silver bullet.” It is simply a starting point. The last post in this series will examine how I might use my personal results.

best adhd medication

Pharmacokinetics (PK) and Pharmacodynamics (PD)

Those are some big words—but not as complicated as they sound.

If we want to learn more about how genes affect ADHD drug response, we need to talk about pharmacogenetics.

Briefly defined, pharmacogenetics is the study of genetic variations that can influence individual responses to pharmaceuticals. Pharma. Genetics.

An earlier post gave an overview of pharmacogenetics. Now we go into more detail on two key aspects:

  1.  Pharmacokinetics (PK): “What the Body Does to the Medication”
  2.  Pharmacodynamics: “What the Medication Does to the Body”

 

 

pharmacokinetics and ADHD
Bi-directional influences on medication response: Pharmacodynamics (“What the medication does to the body”) and Pharmacokinetics (“What the body does to the medication”)

 

1. Pharmacokinetics (PK): “What the Body Does to the Medication”

We’ve all seen those TV commercials for laundry stain-removers with enzymes. These “scrubbing” enzymes find their targeted stains, latch on, and break down the stain.

Guess what? We also have enzymes in our bodies—but not to break down stains. Instead, our enzymes break down certain substances and convert them into other substances. For example, stomach enzymes break down the food you ingest into tiny bits that can be converted into energy.

Among their many functions, enzymes convert inactive drugs into the active form. Once that conversion happens—and only after it happens—we can actually benefit from the medicine.

(We’ll explain examples of an active and inactive ADHD medication below.)

genetic testing

Enzymes are produced by—you guessed it!—our genes. Genes are the “instruction manuals of life.” As such, they specify how to make proteins. Proteins include enzymes and various other molecules. (To learn more, visit “How Genes Work.”)

The small variations in the instructions coded in our genes end up influencing how enzymes are produced and how they operate. In turn, some of these enzymes (and other types of proteins) affect your body’s response to a medication.

Tiny differences in your genes—and thus your enzymes and other proteins—can affect how your body can metabolize (convert) a drug. This also can affect how long the drug stays your body.

In other words, these genetic variants affect pharmacokinetics (PK).

Deconstructing this word’s Greek roots, we have pharmaco (medication) and kinetics (moving, putting in motion). Think of pharmacokinetics as the physiological mechanisms by which the body absorbs, distributes, metabolizes, and removes a drug from the body.

CYP2D6 enzyme and ADHD medication
A rendering of the CYP2D6 enzyme

A Major Player Among Drug-Response Genes: CYP2D6

There are lots of enzymes in humans, but here’s a particularly significant one when it comes to drug-response: Cytochrome P450 2D6, an enzyme encoded by the CYP2D6 gene. It breaks down about a quarter of all drugs, including:

  • Antidepressants such as Prozac
  • Breast Cancer (Tamoxifen)
  • Antipsychotics (e.g. Risperdal, Abilify,)
  • Antihypertensives
  • Pain Killers (e.g. Codeine)

Guide ADHD Medication Dosage with Genetic Testing?

One Size Does Not Fit All

You’ve probably heard people say, “I’m very sensitive to medication.”

What they typically mean is: anything larger than a very small dose knocks them for a loop. By contrast, there are the “nothing phases me” types— and of course plenty of people in between. This in part due to their drug-response gene variants.

For example, there are generally three categories that describe the rate at which humans metabolize drugs, based on the enzymes produced by their gene variants:

  1. Slow, or poor, metabolizers: These folks don’t break down medications well at all. Their genetic differences make them slower than average at converting the drug.
  2. Extensive, or normal, metabolizers: These folks metabolize drugs normally. This is the most common class, representing the type of people for which most drugs are designed.
  3. Rapid metabolizers: This is the opposite extreme to slow metabolizers. These people may require a higher-than-average dose of a medication.

Sometimes these categories are further broken down into smaller gradients, such as ultra-rapid metabolizers and intermediate metabolizers.

Gene Testing for ADHD medication
Where are you in the metabolizer spectrum?

Why Does Metabolizer-Type Matter?

Why is it important to know what type of metabolizer you are? If your body metabolizes a drug too quickly, it can decrease the drug’s efficacy. At the other extreme, if your body metabolizes the drug too slowly, unacceptable side effects may result.

Knowledge, however, is power. If you know that you are a slow metabolizer, you can insist on being started at a lower-than-average dosage. That way, you’ll get a better idea if the drug is a good choice for you—rather than stopping it prematurely due to a too-high dose.   (You don’t absolutely need genetic testing for this purpose, though. Instead, you can follow the wise practice of “start low, titrate slow” (meaning, increase the dose slowly).

Two Types of Drugs: Inactive and Active

Yes, let’s throw in another factor in medication response: whether the drug is inactive or active

Typically, a drug is taken in its active form; it goes to work “as is.” Think of it as the protein equivalent of “ready to wear”.

Other drugs, however, enter the body in an inactive form and require some additional … alterations. These drugs rely on bodily organs such as the liver for conversion to the active form in order to take effect.  Genetic variants play a role here, too!

1. An Inactive Form of ADHD Medication: Vyvanse

Consider the ADHD medication Vyvanse. It starts out in an inactive state.

For this reason, it has been marketed as being less easily abused than other medications in the amphetamine class of stimulants (e.g., Adderall, Dexedrine).

The medication in the Vyvanse capsule becomes active only when it reaches a certain point in the gut. That’s because, at that point, specific gut enzymes convert it into the active form of the drug (lisdexamfetamine). Inactive medications are also called “pro-drugs.”

inactive and active drugs
PRO DRUGS are the inactive forms of drugs, which require conversion by the body to be effective. ACTIVE drugs arrive in the body “ready to go.” Vyvanse is an example of an ADHD medication that is a pro-drug, or inactive form of the medication.

2. An Active Type of ADHD Medication: Strattera

Now let’s consider an ADHD medication in its active form: Strattera. This non-stimulant was the first drug to receive an FDA-certified indication for adult ADHD.

Below is an excerpt from the drug label for Strattera regarding genes that affect its metabolism. By the way, this is FDA-controlled text. That means it is carefully validated and evidence-backed.

Note in the text the aforementioned CYP2D6. This gene influences the metabolism of many drugs in addition to Strattera and is known to have many variants:

CYP2D6 metabolism — Poor metabolizers (PMs) of CYP2D6 [-metabolized drugs] have a 10-fold higher AUC and a 5-fold higher peak concentration to a given dose of STRATTERA compared with extensive metabolizers (EMs). Approximately 7% of a Caucasian population are PMs. (…) The higher blood levels in PMs lead to a higher rate of some adverse effects of STRATTERA (see ADVERSE REACTIONS).

Layperson’s Translation:

Poor metabolizers of Strattera reach a much higher peak blood concentration (5 times higher) than extensive metabolizers. Therefore, they are more likely to manifest “adverse reactions” (side effects). These range from constipation to dizziness, as stated in the drug label.

If you are Caucasian, your chances of having the poor metabolizer form of CYP2D6 are pretty high (7%). The drug label says nothing about other racial groups, but that doesn’t mean these groups don’t have poor metabolizers. It may simply mean there is no data available for them, or the data are simply not listed here.

As you can see, it is very useful to know which variant of a gene you have, whatever the type of drug (active or inactive). This is especially true for CYP2D6 because it metabolizes a huge number of drugs.

Conversely, some drugs are metabolized by only very few genes. So in practice, drug-response genotyping typically involves several genes so as to get the whole picture. (In Part 2 of this series, we list the four genes involved in the genotyping tests we took for ADHD medications: CYP2B6, CYP2D6, ADRA2A, and COMT.)

genotype-specific dosages

Two Scenarios for Slow (Poor) Metabolizers

If you are a poor metabolizer, there are two very different scenarios to consider. Each scenario rests on whether the drug in the bottle is 1) active (ready to go) or 2) inactive (the body must metabolize it into an active form):

1. If the drug is taken in its active form, the poor metabolizer might require a lower-than-average dosage.

If you are a poor metabolizer, you are slower at removing the drug from the bloodstream than the average person. As a result, you could reach a blood concentration that is too high if given an “average” dose. That potentially triggers side effects.

The outstanding question then becomes: how much lower of a dose should you take? Unfortunately, there is no ready answer to that question (more below).

2. If the drug is taken in its inactive form—that is, the drug must be metabolized to become active—a standard dose might not be enough.

What?! How can that be? I just said poor metabolizers risk having too much medication in their system, even with an average dose. How is it that poor metabolizers now suddenly do not get enough from an average dose?

Here’s why: If you’re a poor metabolizer, you are slow at converting the inactive drug into its active form. Therefore, you are failing to reach the dose necessary for beneficial effects, and the drug gets cleared from your system before having had a chance to be converted.

To recap, the slow metabolizer risks two primary effects:

  1. An over-concentration of active medication
  2. An under-concentration of inactive medication

2. Pharmacodynamics: “What the Medication Does to the Body”

Again, pharmacodynamics refers to the manner in which the drug affects a cell. Pharmacodynamics is all about how the drug does its work.

For example, consider the “lock and key” nature of the way a drug typically works with a cell. The “lock” is the receptor, a structure on the cell’s surface that selectively receives and binds a specific substance.  (Like enzymes, receptors are proteins made according to genetic instructions.)

In this illustration, Drug A fits the receptor perfectly. Drug B doesn’t come close. Substance A can bind to the receptor and an action results.

Guide ADHD Medication Dosage with Genetic Testing?

A stimulant such as Adderall or Ritalin interacts with certain receptors with great specificity. That is, it interacts only with those receptors.

This lock-and-key” interaction is imperative for the drug to do its job. By interaction, I mean that Adderall molecules literally slot into those specific receptors in the same way as, well….as your Big Gulp fits snugly in your car’s cup holder.

The snugness of the stimulant with its receptor, however, can vary. Much depends on—yes, that’s right— the variant of the gene that produces this receptor.

Some forms of the gene will produce a receptor with good snugness. That means less stimulant is required to reach a given effect.

Yet, other variants may produce a receptor form with more … looseness. That requires piling more drug (higher dosage) into the “cup holder” to reach the same snug-fitting effect.

Gene Testing to Inform ADHD Drug Therapy

Your Comments and Questions Welcome

  • Are you with us so far?
  • Are you gaining a better idea of how genes can affect ADHD drug response? 
  • Do you see how the simple three-column listing of medications in genetic testing barely skims the surface—and can sometimes steer you away from medications that would work very well for you.
  • Have we started to make it clear: There is no best medication for ADHD—only the medication that works best for you, at the appropriate dose.
  • With the last post (7), we’ll provide a list of takeaway points.

Coming up next: Post 5, The limits of genetic testing for ADHD medications.

—Gina Pera and Dr. Goat

 

 

21 thoughts on “Part 4: Genetic-Testing for the Best ADHD Medication?”

  1. Hello Gina…
    I am not sure if this thread is still active, but since I had an identical question to 1-2 others I thought I’d ask it anyway. It revolves around a Poor (or Intermediate) Metabolizer of CYP2D6 and the use of Vyvanse.

    Like others, I do understand that generally speaking a Poor Metabolizer of 2D6 may need a lower dosage than the average bear of an “active” form of amphetamine, whether it be Adderall, Dexedrine or any within that family.

    The question is when using Vyvanse, an inactive Pro Drug… Does being a Poor 2D6 Metabolizer “generally” require a higher dosage to even achieve a sufficient dosing of the active form after conversion? My adult son with ADHD has at least one SNP (COMT val/val) that may require a higher than normal dosage of medication, but if his Intermediate Status on 2D6 is also hampering the conversion of his 70mg of Vyvanse to the active form that could be a fundamental reason why he constantly says he needs a higher dose and only gets about 6Hrs out of his pill.

    If there is any references showing Vyvanse uses 2D6 to convert that would be good information. Can you share any information on this or elaborate further on this topic?

    Thanks,
    Gary

    1. Dear Gary,

      I am so sorry to only now be responding to your question.

      I read it at the time, thought about it, and I have no idea. 🙂

      I sent my husband a query and failed to bird-dog it.

      I’m wondering if there might be something else going on, more “horse than zebra.”

      Is it possible that your son, like many adults with ADHD, suffers sleep deficits, over-uses electronics, has vitamin or mineral deficiencies, consumes caffeine or nicotine, and/or depends on a stimulant to “propel” him through the day rather than to provide the focus that helps to implement strategies to support Executive Functions?

      One more thought: Does he consume acidifying agents? Check out this post on how citric acid, etc. can affect stimulant performance.

      https://adhdrollercoaster.org/adhd-medications/can-acidic-foods-affect-stimulant-medications-for-adhd/

      I realize that doesn’t answer your question — especially if you’re trying to document the need to your health insurance company.

      But until such time as my husband responds… (I’ll remind him).

      Cheers,
      G

  2. Hi I have 37 years and found out just couple months ago that I have ADHD so my psychiatrist first gave me vyvanse 10 mg to start and try and after 4 hours I start feeling side effects very intense and then I felt like a rush of energy and only lasted 3 hours and then nothing else and later on in the afternoon around 4pm I was completely awake like alert and that night had insomnia and then I went up in the dose until 40 mg and I quitted the side effects were very intense and the other days I didn’t feel anything that can help adhd symptoms and you said that vyvanse and poor metabolism need a higher dose I think I’m going to try vyvanse again and this time go higher in dose after vyvanse I changed to generic adderall and I started 5mg up to 40mg in a day and nothing happened I didn’t see any changes on ADHD symptoms so I switched to generic ritalin instant release methylphenidate and I’m in 20 mg now but only lasted 1 hour and then goes away I started at 5 mg twice a day and nothing then going up until 20 mg and I thought that small dose I was going to start seeing the benefits of the drug but nothing please help me what do you think my Dr. Is also prescribing me wellbutrin but I stopped taking it because I didn’t work at all and I was taking lamotrigine too but I stopping that one too because is not doing anything
    Thanks in advance

  3. I’m a rapid metabolizer for dexedrine, and I’ll tell you, finding a doctor who’s willing to treat me with the doses I need has been a nightmare. Finally I’ve found a competent doctor who realizes what any specialist with nine years of medical training should know, that some people are simply rapid metabolizers of certain medications. The most recent “doctor” I was on a wait list to see, told his wife, who was my GP, after receiving my medical record, awash with misdiagnoses, and failed medication attempts, that I must be suffering from “drug addiction”, never so much as having tried marijuana in my life. Of course there was no drug I had taken, except sleeping pills, that was addictive, (I did need them to sleep sometimes), but being a Canadian doctor, he didn’t know enough to understand that ADHD stimulants aren’t addictive. Hope he’s learning the basics now, but I certainly wouldn’t bet my health on it. He told his wife I was an “inappropriate referral”, and not only did I not get to see him, I had been told I had to give up my place on a waitlist, if I wanted to be put on his, after months of waiting to see another specialist. Of course there’s limited accountability in the medical profession, certainly up here, so it doesn’t matter that his abusive “diagnosis” cost me a year and a half of my life, and delayed my already severely delayed education, by that amount of time.. but, he has a medical degree, so he must be in the right. Right now I have to go back to my doctor to ask for a second dosage increase, because the vyvanse has simply never been high enough for me. I end up taking 60 mg more, then going without for six days at the end of the month, but that won’t get me through five chemistry courses this semester. What a pain. I wish I knew exactly what tests I need to take to determine what level of vyvanse and evening dexedrine IR I need. I know what dose of Vyvanse I need, about 180 mg/day + IR for the evenings, but I’d like to have it on paper, so that when my doctor retires, I’m not simply at the whim of a mental midget like the one I was wait listed to see.

    1. Hi Ben,

      I’m sorry to hear of your struggles. Canada has two excellent advocacy and professional groups: CADDAC and CADDRA. But, alas, they cannot manage the entire NHS insofar as ADHD.

      CADDRA does make available as a free download it’s excellent treatment guidelines: http://CADDRA.ca

      As I read, I was wondering if you’d tried Vyvanse, as it is time-release Dexedrine. Then you mention you have.

      Your doc might invite trouble by documenting your need for that dose without any independent support.

      Maybe getting the genetic test would solve a lot of problems for you. I suppose the NHS doesn’t pay for the Genesight testing. I see this company. But as with the American offerings, I do urge caution in interpreting the results. (That’s why we wrote a 7-part blog post!) https://biogeniq.ca/en/

      In the meantime, have you tried strategies for reducing your need for that high dose? That is, are you using all the environmental supports to help you structure your time and focus? Calendars. Planners. Breaking up big chunks of studying into smaller ones, etc. Also, good sleep, exercise, and diet? Maybe look into amino acid precursors (e.g. L-Tyrosine).

      While not an answer in and of themselves, doubling down on these strategies might help you to maximize the dose you can get.

      I know you realize this, but I need to mention: It’s not advised to use the stimulants as “performance drugs”. In other words, your ADHD treatment should be supporting you in living a more balanced life, not tackling five chemistry courses.

      Good luck getting the help you need.

    2. Hi Dr. Pera! Thank you so much for your thoughtful response, my gosh, as I read my initial message, I sound like such an angry person. Now I’ve dropped two of the chemistry courses, so I’m sane again. I apologize for my tone in the initial message.

      I think the genetic testing could, potentially? solve some of the problem for me. At least, either way, if the results were somewhat definitive, it would put my mind to rest, and give my doctor documentation to support any “off-label” treatment, that might be necessary.

      Can I ask what lab/company you’d recommend for testing the genes implicated in vyvanse/dexedrine IR metabolism? You mentioned genesight, could that be the one to go with?

      What level of clarity could the testing give for a situation like mine, where my dosage, (130 mg), still really seems to low? I need to read the rest of your blog!

      Thanks so much,

      Ben

    3. HI Ben,

      No problem. I thought you just seemed stressed. I get it!

      I already offered the name of a company in Canada doing gene-testing. Otherwise, I know none except Genesight.

      I’ve just learned that here in the U.S., the FDA is actually specifying that some medications are highly affected by metabolism. I haven’t seen the stimulants on the list of 200 or so medications already documented.

      g

  4. Pingback: Can Foods, Acids, and Antacids Interfere with Stimulants? - ADHD Roller Coaster with Gina Pera

  5. Hi Gina,
    Your blog is very helpful and informative. I’m still slightly confused on just one point. You explained that a vyvanse dose would need to be raised in poor metabolizes to achieve the same effect. Were you talking about poor metabolizers of cyp2d6 or a different enzyme. I don’t mean this in a challenging way I’m just really confused because on rxlist and on vyvanses website it says lisdexamfetamine is not metabolized By cyp450 enzymes but instead it was metabolized into dextroamphetamine in red blood cells via hydrolysis. When I had gene testing done it showed that I was a poor metabolizer for cyp2d6 and then showed in large print”ADHD Medications metabolized by the CYP2D6 enzyme: amphetamine salts, dextroamphetamine, atomoxetine and Lisdexamfetamine” and this seems to support what you were stating in this post. If you could please clear this up for me I would really appreciate it because between being a poor metabolizer and being on Bupropion, which is a strong inhibitor of CYP2D6, it seems that I would not be efficiently metabolizing vyvance into its active form. Thanks so much for your time.

    1. Hi Scott,

      My husband and I are reaching the end of our vacation. We will try to answer this in a few days, but I think it’s really best if you ask your physician.

      Anecdotally, though, I haven’t seen Bupropion and Amphetamines being a great mix — too much potential for anxiety.

      best,
      g

  6. This is such an informative article, thank you! After years of adverse drug reactions I had a physician casually remark that I must be a fast metabolizer. This gave me something to research and eventually push for some genetic testing. It had never been done at my clinic, so they were unsure what to order, but I did get 2D6 and one of the other CYP enzymes tested. Turns out I am a poor metabolizer for 2D6, which explained my adverse reactions to the Beta blockers and tricyclic antidepressants. I needed about 1/4 the dose of a “normal” person. The information obtained from the genetic testing allowed my specialist to tailor medication doses to my metabolism, allowing me to use drugs we had previously thought I could not tolerate.

    In years of researching this topic, I haven’t found such an excellent resource with so much information all in one place in layperson language. I will be sharing this article from now on when I want to introduce others to the concepts of drug metabolism and genetic testing. i feel this testing was crucial to my migraine treatment, yet my physicians were not very familiar with it. Many other patients are most likely in the same sitation, and will have to educate themselves and their doctors in order to get the help they need. Thank you again for this valuable resource!

    Sincerely,
    Cristy

    This is a table I find useful, that may help other readers:
    http://medicine.iupui.edu/clinpharm/ddis/
    CYTOCHROME P450 DRUG INTERACTION TABLE

    1. Hi Cristy,

      I’m thrilled that you find our (Dr. Goat and me) tedious work helpful!

      It’s said that medical-science information takes about 20 years to trickle down to the clinical level. But I knew about the CYP enzymes at least 15 years ago. How is it that some docs still don’t know? It’s a major flaw in our medical “system.”

      Thanks for all you do to educate and support healthcare consumers!

      g

      P.S. And that’s a very helpful table. tx!

  7. Pingback: Post 7: Gene-Testing To Inform ADHD Drug Therapy - ADHD Roller Coaster with Gina Pera

    1. I am confused by the Vyvanse pharmacology too, Scott! I hope you share if you get more info. I will say that talking to my doctors has never been helpful as I am just as likely to have to explain metabolic issues to them as the other way around. However, I was able once to get sent to a clinical pharmacist who was able to at least shed some light on my genetic PM 2D6 results (which my geneticist and prescribing physician don’t understand). This was not a billable appointment as they don’t see “patients,” however maybe other patients in such confusing circumstances can see one? Otherwise, my pharmacist has been the most help (at least providing me with a table of the enzyme substrates, etc). Good luck!

    2. Great idea, Cristy. I often will refer such questions to the nearest university-hospital pharmacist. They are typically very helpful!

      g

    3. Dear Gena,
      thank you so much for all the information you share! I’ve been diagnosed with ADHD a year ago, read your book and discovered your blog only about half of a year ago, so if my question have been answered somewhere else, please just direct me to the link. My confusion is about your two following points:

      “1. If the drug is taken in its active form, the poor metabolizer might require a lower-than-average dosage.
      2. If the drug is taken in its inactive form—that is, the drug must be metabolized to become active—a standard dose might not be enough.”

      What happened to me, is that I first was prescribed generic Adderall instant release 5 mg (blue pill with imprint cor 130), and wow!! — in about 5 minutes (!) after I took the pill everything I saw suddenly had dimensions like in childhood, I was calm and normal, stopped trying to walk into the walls instead of doorways, galloping down my food instead of chewing it, and was consistently in a good mood even after the meds stopped working. I even went to bed on time and got up as soon as I woke up, instead of lying in bed for hours in the morning like I used to. It worked! But my body could not take it: too much numbness when the meds wore off, blood vessels constricting to the point of pain, and terrible muscle pain around old injuries. So my doctor suggested Vyvanse, just 10 mg. And then it started: anger! headache and terrible eye pain! sleeplessness! We switched to brand Adderall instant release 5mg (Teva), and then that anger again (much less) with the full dose, — so I started cutting the pill down to 3/4 and still felt like I was hyperactive me again and on tons of caffeine, the latter especially when the meds wore off, doing 10 things in one day and barely sleeping. At about 1/2 of the pill I suddenly relaxed and slept right after I took it, but in the several next days the sleepiness turned into tiredness, then anxiety and feeling of indifference to anything came right after I took the dose, and feeling of being tearful, depleted, and irritated closer to the bedtime. No other meds or medical conditions were involved, so we discontinued the Adderall all together, and now I’m waiting for my pharmacy to get brand Ritalin.

      So here is my confusion: would not it make more sense, according to metabolism reaction, that I was supposed to take, and process, Vyvanse even in higher than 10 mg dose? I apologize if I misunderstood your explanations. I see your point about genetical testing, but concerned that it will confuse me even more.

      Sincerely,
      Lena

    4. Hi Lena,

      Wow, that’s tough. To have such a “miracle” happen and then go away.

      There are MANY reasons to explain what you experienced.

      If you had the “angry” reaction to Vyvanse at only 10 mg, it might be unrealistic to expect better from a higher dose.

      But it will be important to give the Ritalin a trial first before going down the “metabolic” rabbit hole. 🙂

      g

  8. Pingback: Part 6: Gene-Testing To Inform ADHD Drug Therapy - ADHD Roller Coaster with Gina Pera

  9. Pingback: Part 5: Gene-Testing to Inform ADHD Drug Therapy - ADHD Roller Coaster with Gina Pera

  10. Dr. Goat and Gina,

    This series has been great with a wealth of information on a complicated but crucial topic. Thanks for doing it!

    Just wanted to point out that ‘poor metabolism’ is a double-edged sword. There may be more side effects at standard dosages, but response rates may be higher as well. (Strattera, for example, has higher response rates in poor metabolizers than extensive metabolizers.)

    Your advice to go slow and low when trialing medications in poor metabolizers is absolutely correct, and I just want to underscore the point you’ve been making that medication selection is very complex, that there are are many factors, not just the gene profile, that have to be considered. The notion that one should “try this drug” first, next or last based on the pharmacokinetic profile is a bit of an over-reach by Harmonyx.

    When someone with ADHD has issues with substance use, OCD, anxiety, severe tics, dyslexia, insomnia, etc., we generally begin with non-stimulants regardless of whether Harmonyx says to use them first or last. In such cases, we use the pharmacogenomic profile to adjust the dosing only, not the priority.

    Thanks for indulging a nerdy comment!

    Oren Mason MD
    Attention MD
    Author — Reaching For A New Potential

    1. Hi Oren,

      Thank you so much for weighing in—and making such important points.

      We will be wrapping up with some of the issues you mention, but we figured the incremental approach would work best in explaining these complex factors.

      I, too, am most worried about the “try this first/next/last” recommendations being taken literally by patients, as I’ve already heard some parents of children with ADHD report.

      Accurate diagnosis, published data on first-line ADHD medication response rates, and the facotoring in of co-existing conditions is more important.

      Thanks!
      Gina

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