ADHD Medication Gene-Testing Benefits and Limits — Pt. 5

Genetic Testing Benefits & Limitations

What are the benefits and limitations when it comes to using ADHD gene-testing to guide medication?  That’s the topic of post 5 in this series: Genetic Testing for ADHD Medications.

Throughout this 7-part series, we explain all the factors involved—defining terminology, offering examples of our own tests, and more. There won’t be a test!

Here in Part 5, Dr. Goat and Gina:

  • Help you to decide how and why this gene-testing might be useful for you or your loved one
  • Offer three common scenarios for which testing might be informative
  • Remind that test results are only one piece of the puzzle.

Get ready for this week’s simple metaphor to explain complex science:  You can’t stay warm in the winter—even if your heating system is functioning perfectly—if

  • Your house has air leaks,
  • There is no insulation in the attic, and
  • The windows lack caulking.

The Potential Benefits & Limits of Genetic Testing for ADHD Rx

By Gina Pera and Dr. Goat, PhD

Part 5: Gene-Testing to Inform ADHD Drug TherapyAs we’ve seen in previous posts, genotyping of drug-response genes tells you how well certain aspects of your drug-response machinery are working.

Consider genotyping as one part of the puzzle. To simplify this complexity, think of it in terms of a house inspection that inspects only how well the heating system works. For example:

  • Furnace—How efficient is it?
  • Radiators—Clear or clogged?
  • Heating ducts—Insulated or leaky?

Keep in mind, though: These factors all relate to the heating system only. That’s just one aspect of keeping the house warm. We who grew up with hard Canadian winters know: The heating system is only one part of the equation. In this metaphor, the heating system is the information you receive from genotyping.

Part 5: Gene-Testing to Inform ADHD Drug Therapy

A Useful Metaphor: A Home Heating System

Consider other factors beyond the heating system, to name a few:

  • Wall and window insulation
  • Flooring
  • Outside temperature
  • The occupants’ preferred indoor temperature

Part 5: Gene-Testing to Inform ADHD Drug Therapy

Part 5: Gene-Testing to Inform ADHD Drug Therapy

Part 5: Gene-Testing to Inform ADHD Drug Therapy

Part 5: Gene-Testing to Inform ADHD Drug Therapy

Obviously, these factors also affect the desired goal (a comfortable inside temperature for the house’s occupants).

In other words, you might know that the heating system is working well. But that doesn’t necessarily mean that the house’s indoor temperature will be comfortable. You have to consider the other factors mentioned above (insulation, outside temperature, etc.).

Part 5: Gene-Testing to Inform ADHD Drug Therapy



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The same applies to genotype data. It will tell you how well one part of the system is working: the drug-response genes. But that’s not the whole story.

There is a huge gap between

  1. How the proteins produced by those genes function at the molecular level, and
  2. The final therapeutic effect on large numbers of cells in the brain

And that means we find clear limitations as to the ADHD gene-testing benefits.

The involvement of other factors comes into play, including:

  • Age
  • Co-existing conditions (including not only psychiatric conditions but also cardiovascular issues, diabetes, chronic pain, etc.)
  • Health status
  • Nutrition
  • Other lifestyle factors

Also, keep in mind: We have a large body of published literature that tells us about response rates to the various medications used to treat ADHD. This information comes into play, too.

For more than a decade, I (Dr. Goat) have taken a stimulant medication listed in the “Consider this last” column of my gene-testing for ADHD medications. You’ll learn more about that when I personally address my application of test results in the series’ next post.

Does this mean that it isn’t useful to know about your specific drug-response?  No. It is absolutely useful to understand, at least in part, the performance of the crucial machinery that affects your ability to process and respond to a drug.

More Gene-Testing Benefits: Three Scenarios

Given all that, we will repeat and expand upon our take on the three scenarios as to when and how to use results from drug-response genotyping:

  1. Just beginning medication
  2. Been on medication a while but aren’t happy with the results and/or side effects
  3. Considering adding a medication

Let’s examine these scenarios one by one.

Scenario 1: You’re just getting started with ADHD medication

You are diagnosed with ADHD and ready to proceed with drug therapy. Genotyping data can help you decide:

  1. The Order in which you want to try medications
  2. The Dosage you might want to start with

Dosage is tricky. That’s because it’s not a yes-no decision. If you’re a poor metabolizer for a so-called active drug, you are likely to need to start with a lower dosage. But, how low? Frequently—or perhaps even typically—no one really knows. It’s not at all clear how one should pick a starting dose.

It’s basically a crapshoot.

Take the example of Strattera (atomoxetine). The peak blood concentration reached by poor metabolizers is five times higher than normal. Therefore, to be on the safe side, you might want to start with half the normal dose. Even then, this dose might still too high (thereby potentially triggering side effects). Or the opposite: It might be even too low to get a beneficial effect.

Why start at only half the dose rather than 5 times lower? The rationale has to do with the gap between what genotyping tells us and all the other factors that affect how you might respond.

Here’s some background info on Strattera/atomoxetine mechanism of action.

So you may well ask,

what’s all this fuss

about genotyping?

Part 5: Gene-Testing to Inform ADHD Drug Therapy

In other words, think of starting at half the dosage as a neutral bet. You may not get much beneficial effect because the dose is too low, but you minimize the risk of side effects.

If you observe few or no side effects, you might consider increasing the dosage, especially if you’re not sure you are getting beneficial effects. You would continue to increase until you start noticing side effects.  At that point you might want to back down some. (Ideally, the prescribing physician will be using rating scales and other methods to help you track progress and side effects.)

Gina’s book already makes that recommendation about medications in general:  to  “Start low and titrate slow.” (Titration is the process of gradually adjusting the dose of a medication until optimal results are reached). So you may well ask, what’s all this fuss about genotyping?

What about the potential ADHD gene-testing benefit?  It  lies in providing hard data —a rationale as to where to start in your dosage, as well as which medication you might to begin with. Genotyping will help inform those decisions, but it’s not the whole picture.  The alternative is starting blind as to how your body is likely to metabolize and react to the drug.

For many people, starting blind is not an issue. It’s how ADHD medication selection typically goes.  But it should go methodically. Again, see Gina’s book chapters on medication. She was educating about this in 2008 and earlier!

Part 5: Gene-Testing to Inform ADHD Drug Therapy

Scenario 2: You are having problems with a specific ADHD medication

Perhaps you’ve been taking a medication for a while. You finally decide the side effects are intolerable, and you want to try a different medication. These side effects might, in fact, be manifesting because your dosage is too high. This might be because you have a variant of the CYP2D6 gene that confers slow metabolism of an active drug, such as Strattera.

Knowing this fact might help you justify a decision to simply lower the dosage (instead of switching to another medication altogether). In that way, you can continue using a drug that is well suited to you.

This point is important! The universe of medications suitable for ADHD is quite limited. There are many formulations and delivery systems—and that can make a big difference. But the effective ingredients themselves? Few in number. Before discarding a drug, we should first address factors that might explain its poor performance. Again, perhaps a simple dosage adjustment to match your biology is all that is required.

Moreover, a single gene can influence the effectiveness of multiple drugs (e.g., CYP2D6). Therefore, it is entirely possible you might have similar side effects with another drug for the same reason you originally ditched the first one. In other words, you’re a poor metabolizer for both.

Case in point: One of the main stimulant medications on the market, namely, amphetamine (the active ingredient in Adderall), is also processed by CYP2D6, so whatever variant of this gene you have will likely affect how you respond to both Adderall and Strattera. That’s why knowing the profile of your drug response genes is clearly helpful.

Scenario 3: You are considering adding an ADHD medication

This is basically a variant of point #1, except with the added complication that you are already taking one or more drugs.

This is a common scenario. Most adults with ADHD have at least one co-existing condition, such as anxiety, depression, and bipolar disorder.

Because drugs can interact with each other to the detriment of all—and there is often little data in the literature on these interactions—selecting an additional drug and determining its dosage is even trickier.

Knowing that the additional drug is metabolized by one of the drug-response genes is helpful. Why? Because drugs can “gang-up”—thus overwhelming the body’s ability to metabolize them. This comes with all sorts of consequences.

 

ADHD psychodynamics in the context of gene testing to guide medications

For example, if you know up-front that you are a slow metabolizer due to a single gene involved in the metabolism of both drugs, you might better assess the safety and dosage with which to begin the second drug.

ADHD Genotyping Caveats and Limitations

As emphasized above, many factors beyond genetics influence the outcome of drug therapy. Many of these factors remain unknown to us. That means we are operating in partial darkness in the best of circumstances.

For these reasons, drug selection and dosage decisions will necessarily be imperfect.  We simply don’t have all the information necessary to even approach optimality. That underscores the importance of being conservative and cautious in selecting ADHD drugs and their dosage.

This is especially true for a condition such as ADHD because of its chronic nature. That is, you likely will take a drug for a long time.  Because the range of available drugs is limited, it is crucial to carefully evaluate a drug before discarding it.

Don’t feel bad if you get the sense that ADHD medication treatment is a seat-of-the-pants decision-making exercise—because that is mostly what it is.

Published research tells us a great deal about medication response for large groups of people with ADHD. Research tells us much less when it comes to any one individual.  Fortunately, genotyping of drug response genes means you can now do the individual decision-making with perhaps a bit more light thrown unto this dark landscape. As long as you know what you’re looking at!

Up next at this ADHD Roller Coaster series: Gene-Testing To Guide ADHD Medication Choice—Part 6

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. This Post: Reminds that genotyping data provides only one piece of the puzzle.

 

6. A closer look at Gina’s ADHD genetic testing results

Gina’s Gene-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.

 

 

We welcome your comments and questions, especially if you are an ADHD-specialist physician with experience in this issue.

—Gina Pera and Dr. Goat

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19 thoughts on “ADHD Medication Gene-Testing Benefits and Limits — Pt. 5”

  1. Thank you for your website it’s amazing. I think I’m going to be getting to know it very well! I have just been diagnosed with ADHD and will soon start on medication. When you say to start low and titrate slowly … how slowly should I go? I’ve chosen to start Elvanse (Vyvanse in the U.S., I think?) at 20mg per day for two weeks and the increase to 30mg for two weeks assuming all has gone well and an increase is indicated.

    Does that speed sound about right?

    1. Hi Eimear,

      Glad to have you aboard! ADHD Roller Coaster is the first website on adult ADHD (of any kind) — and the longest running. Since 2008.

      As to your question, it really depends. I cannot advise you medically, but I can relay the basis consensus and standards.

      https://www.vyvanse.com/doses

      The lowest Vyvanse/Elvanse dose is 10 mg. The “starting dose” is 30 mg. (But I’ve never found starting doses to be useful. They are almost always too high.)

      Your starting at 20 mg seems a prudent middle-road. After monitoring for two weeks, increasing to 30 mg. seems prudent as well. JMHO.

      All that said, it depends on your neurochemistry, general health, any sleep debts, caffeine consumption…. all kinds of variables.

      Good luck!
      Gina

  2. I went through the titration and the past year and a half was hard work. Now I am questioning my sanity on the ADHD front. I work as a software developer, which means I need to focus on one task during the day.

    Methylphenidate – on 100mg I had insanely high blood pressure.
    I would notice I can focus easier on 20mg.

    Lisdexamfetamine – went up to 60mg and I was idiotically aggressive, going from zero to sixty in seconds. but 20mg would put me in the nice zone where I would hyperfocus for 6 hours straight forgetting about life outside.

    Now riding Atomoxetine 100mg with feeling sick the first hour after but I struggle with focus. Added 5mg of methylphenidate, which goes up to 10mg 2x a day for focus.

    I am so tired of it, I have stumbled upon your blog and this makes so much sense, especially the house analogy. I have my nutrition on point, I am active physically and mentally but I do struggle with meds and dosage. I am considering doing the DNA test for ADHD – what kind of meds would suit me best, am I a high metaboliser or slow but still feels like snake oil and I don’t have confidence in it after reading your article… is it worth doing it in my position?

    1. Hi Jakub,

      Here’s my take on these things. If you can easily afford the testing, sure, why not. But, I’d be prepared to not take the results as carved in stone.

      They are too “dumbed down”. In the hands of a clinician who can actually put the data in context, something in the results might be useful. Are such clinicians easy to find? No. More likely: an over-confident clinician who takes the results at face value (red, green and yellow columns as clear-cut).

      I’m preparing Course 2 in my online training now, on sleep and medication. Course 1, the foundational course, is available now. https://adhdsuccesstraining.com/solving-your-adult-adhd-puzzle-for-couples-and-individuals/

      If you’re not getting proper help with translating this highly variable syndrome (ADHD) into your personal manifestations of it, I recommend that you do that. It can be an essential part of making progress. But this kind of evidence-based therapy is almost impossible to find. That’s why I created it.

      Late-diagnosis ADHD adds further complexity, and sometimes it’s the old habits that sabotage even the most learned approaches to medication.

      For example, what is your sleep routine and how much sleep are you getting? How are you approaching your work?

      My husband is a biocomputational scientist. He knew the medication was truly working when he was able to get through a big chunk of coding without making errors. This markedly improved his mood!

      But he was also able to see that, before medication and diagnosis, he was very impulsive in his approach to work. He’d jump into a project without mapping out a plan. On paper. On the white board. Whatever. Then he started taking time to do that.

      I am concerned for you, Jakub, in taking those huge doses. 100 MPH, 100 atomoxetine.

      Sure, it might be that you are an ultra fast metabolizer— and, in my view, that is the most useful takeaway from this testing.

      But I’m wondering if perhaps you are asking too much of the medication — and not being strategic with how you work, using external supports for Executive Functions (e.g. plan your work and work your plan), etc.

      Does that sound possible?

      Gina

  3. ADHD in Denial

    Hi Gina,

    You’re definitely very dedicated and we so need people like you! I’m just jealous as I can’t commit to anything for more than 5 mins before tedium sets in.

    Plus I’m British, got to make a joke about everything, it’s in our DNA.

    Definitely agree with you re your comment what’s the point of access to A&e if you’re hobbling along in life. Mental health has always been the poor relation in the NHS. ADHD is still seen by many in society as a moral failing and public opinion definitely holds some sway as to what treatments are funded.

    Another example pretty much all NHS authorities have reduced or withdrawn treatments for IVF as infertility is seen as a lifestyle choice. I’m pretty sure the WHO doesn’t think like that. Oh and the arbitrary criteria for who’s eligible such as if one of you already had a child you get zip!

    My husband and I watched his daughter get married the other week. So er yes that was us, even though I met all the other criteria including age. The NHS is chronically underfunded, parts of it have been sold off and privatised by stealth! The worst of both worlds.

    I pay for private health insurance, some lucky people get it through work. It doesn’t help people with ADHD much though as insurance companies don’t cover pre existing conditions. I did manage to get them to pay half the cost of the original assessment though.
    Although my premium went up as a result!

    My family pressurised me into getting cover due to family cancer history. Cancer Another problem with the NHS, the treatment and care first rate. Waiting times appalling so we have lower survival rates than other European countries.

    Anyways I finish my rant, we really need people like you Gina to advocate for us and spread the word. I think slowly people are starting to gain more of an understanding of ADHD and hopefully will be along the lines of how ASD is now seen.

    One promising thing here in the uk is people are becoming aware of ‘right to choose’ in the NHS and can bully there GP into referring for online assessments, with NHS approved providers, aka much reduced waiting times.

    Might end up going down that route myself, although really don’t want to go down the painful route of being reassessed. Have a good week as I expect it’ll be Monday when you see this 😉

    1. Hi ADHD in Denial,

      Thanks for the kind words. I totally get it. One client the other day teased me by calling my office bookshelves a “micro-aggression.” 🙂

      https://www.facebook.com/GinaPeraAuthor/posts/4162475830497915

      I am actually working a bit today — need to create an “explainer video” for my new online course and am procrastinating. 🙂

      I am also very tired. Here is the course, BTW:

      https://adhdsuccesstraining.com/adult-adhd-solving-the-essential-puzzle-pieces-for-couples-and-individuals/

      I understand your hesitancy to be re-assessed. I’ve heard from more than a few Brits going through this — it feels like running a dangerous, invalidating gauntlet.

      I advise them to get their ducks in a row — gather data, based on the diagnostic criteria, offer examples, evidence. Do NOT be passive and trusting. Keep it concise and pointed.

      Thanks for those details. I did not know that your private insurance doesn’t cover pre-existing conditions. Wow. What’s the point then.

      Our Obama-era healthcare reforms finally did away with that, which was huge for millions of Americans.

      But many Americans, especially on the left, just don’t know what they have. They’ve been told by Mr. Sanders (a man of little accomplishment over 40 years in Congress) that single-payer is paradise, and everything is free. (In his earlier “writings,” he claimed that yoga could heal cancer and that young teen girls should submit to their boyfriends’ demands for sex, no matter what her parents say……[roll eyes])

      Many Americans also don’t understand that “you get what you pay for.” One insurance company will have perhaps 100s of plans from which to choose, to best suit your needs, and plans will differ in out-of-pocket expenses, drug coverage, etc. But if consumers don’t choose wisely and end up surprised, they will blame the insurance company.

      Reforms also reined in the insurance companies. The larger problem now is with medical device makers. But Trump also appointed a FDA chief who pushed through dozens of inferior generics, over-riding FDA scientists’ protests. Now we are stuck with them, including about 16 Concerta generics that are little more than generic Ritalin.

      Meanwhile, covert forces throughout the world, including US and UK, sow division, disinformation, and chaos. Those who don’t see beyond the superficial slogans—who get “educated” on Facebook and Twitter—risk making everything worse, for all of us.

      Getting off my soapbox now. 🙂 I just get frustrated with all the potential for good in the world — ruined by the unthinking dancing to the tune of the sociopathic.

      g

  4. ADHD in Denial

    Hi Gina,

    really interesting read. Just about got, through it all, lots of scanning 😉 .

    Was interested to hear that you can be a slow metaboliser and need a higher dosage of an inactive drug like Vyvanse. I took one 30mg pill of Elvanse an inactive drug at 9am and I was ‘off my face’ aggression uncontrollable physical hyperactivity, euphoria zero inhibition and didn’t feel back to ‘normal’ until 2am. I then tried Methylphenidate. An active drug right? I was advised to cut the 5mg tabs in half due to the experience on Elvanse. Very subtle effects I knew I was on something at 2.5mg, slight constricted throat feeling other than that rather pointless, so tried a whole pill the next day. Complete calmness for about 2 hrs no screaming and swearing at the computer, amazing focus, then I started to feel irritable towards my husband. I took a 1/2 to smooth it out and was ok again. I was then advised to take 1/2 pill 3 times a day for a couple of weeks and than try 5mg whole pill.

    So I did this and found the throat constricting side affects went and was really looking forward to sitting in bath when my husband wasn’t around to irritate me and chill out with the 5mg. Be the first time in around 20 years. So anyways I ended up taking the 5mg on a day off from work only to find my usual morning irritability didn’t go, no difference to being on 1/2 a tab. How disappointing! So anyways I persevered with 1 whole tab in the morning followed by 2 1/2’s spread out through the day. If I tried 1/2 a tab more I got insomnia and more importantly after a few days started getting heart palpitations.

    So I’m stuck on a puny 10mg a day max. Was convinced not doing anything certainly not helping with busy head, memory, motivation yada yada, so tried to get off it My brains so used to the drugs if I take 1/2 a pill less a day I get horrendous insomnia and racing thoughts at night. I’ve tried to get off the pills twice now, the second time I managed to reduce over a few weeks, however now think they were doing something mostly for my mood, physical pain and bizarrely regulating my cycles so this week back on the process of trying to increase. 1/2 a tab too much and insomnia and racing thoughts abound.

    Probably should go back see my Pyche, not keen on having to pay privately though. In the UK it’s takes ages for diagnosis on the NHS. Was hoping for shared care once been diagnosed, (where GP takes over the prescribing) however my GP have said no as it was private assessment and that I have to be reassessed by NHS psychiatrist and the waiting list is long! Most places it’s a minimum of a year some places up to 5 years. Adult ADHD isn’t really a priority over here. I constantly have doubts about the diagnosis and spend way too much time researching it. Kind of like health anxiety, only for mental health. Keeping on the tablets is a chore 3 times a day and hubby disregards the diagnosis and the pills. So far this years been difficult, barely time to process the diagnosis and get use to medication, which came out of a difficult couple of years for myself, when hubby’s hit with redundancy and a close relative dying in the same week. BTW I have suspicions I’ve chosen a husband with it too. It doesn’t rain it pours!

    Sorry I’ve digressed so much from my original thought which to cap is that I was sensitive to both active and inactive drugs. Not sure they do genetic testing for that here in the UK. Would be interested in finding out though. Anyways thanks again for the article.

    1. Hi “ADHD in Denial” 🙂

      I think you’ve earned some kind of medal…or something. That’s a detailed series!

      I wonder what type of methylphenidate (MPH) pill you are taking? The difference among all the many MPH choices comes down to one thing: The delivery system.

      How fast, how much, it’s delivered to the system, over time.

      Generic Ritalins (maybe what you have) can be all over the map, company to company, lot to lot. The dyes and fillers can create their own side effects.

      In general, though, the immediate-release MPH create a “roller coaster” for many (not all) people — too-sharp ups and downs. If you could try a long-acting, you might do better and won’t have to make a major part of your focus when/how much to take each day.

      Yes, I’m well aware of the situation in the UK and so many other countries. It’s one reason I oppose single-payer healthcare here, because I’ve seen what happens when the government beancounters alone decide who merits treatment for what: Adults with AHDD always come out the losers.

      Squeaky wheel gets the grease. Maybe you can identify some NHS GP who would be more sympathetic to your medical needs.

      Good luck!

      g

    2. ADHD in Denial

      Thanks for the quick reply Gina, me thinks you’re a workaholic .

      Yes you hit the nail in the head all my focus is taken managing and remembering to take pills even with alarms. It means I feel like I can’t move on and maybe start tackling other neglected areas, like a constant reminder. Makes me want to put it all in a box and close the lid. One of my many coping strategies over the years. Think I’m going to make that appointment!

      Interesting what you say about single payer healthcare. Without getting too political, although it’s a loser for adult ADHD it keeps the costs down for other important treatments and importantly means I don’t have to ever worry for emergency medical assistance. That’s important when you have ADHD right as I’ve spent a lot of my adult life in insecure poorly paid jobs or unemployed. Some employment in quite prestigious exciting back stabbing industries, mostly in low status boring customer service related hell holes.

      I love to live dangerously and now I understand why . I guess it’s swings and roundabouts and healthcare is a difficult beast. Raising awareness of the financial costs of untreated adult ADHD is probably the only way forward here in the UK, just think about all that tax I could have been paying if I had a steady career over the years. All those government subsidise attempts to get my undergraduate degree. 3 to be precise and then the cost of my mental health to the NHS at least 3 unsuccessful rounds of CBT over the years trying to treat ‘anxiety’. Always interested to hear from other points of view re healthcare systems so thank you as it’s always the same old NHS is so wonderful rhetoric here in the UK.

      The NHS is a beautiful thing, it’s imperfect beauty though and has plenty of room for improvement!

    3. Hi again,

      A workaholic? Some view me as dedicated.:-)

      I happened to be at my desk when the notification came.

      I get your point. The NHS does many good things.

      But when it completely ignores a condition that, left untreated, is a setup for all the costly conditions it does “treat”? Makes no sense to me.

      What good is having access to the ER if you’re just hobbling through life?

      take care,
      g

  5. What ADHD meds do NOT metabolize through CYP2D6. My son needs it so badly but he’s a poor metabolize.

    If anyone wants a gene test for metabolizing, GeneSight is $200 and does ot for anti depressants but you can use the same information for metabolizing. It checks almost every enzyme.

    Non-white people have a high rate of slow metabolizing cyp2d6. And medical community brushes it off. Of course. Like this article, a great one but using caucasians as a measurement for “standard”. I found my information in peer reviewed articles, the author was LAZY about this. Especially given the thoroughness of everything else.

    1. Hi again Chris,

      Let me get this straight: You are castigating us as “LAZY” despite the very hard work my husband and I put into a SEVEN-Part series on a subject that NO ONE else is covering in any depth at all?

      Specifically, you are criticizing us for not including comparative data for Caucasians, African Americans, Asians, etc.?

      Do you realize that this series is already so detailed, most readers can’t even get through it?

      Moreover, I’ve seen no definitive data on that topic — and lots of conflicting data. As one would expect, given that the concept of “race” can be a squishy one, genetically speaking.

      I find your calling us LAZY as ill-informed, arrogant, and rude.

      If prescribers did what they were supposed to do — and what we emphasize in this series, start low and increase slowly — there would be little to no need for this genetic testing or “racial” differentiation.

      We don’t need to identify alleles and mutations, etc.. to know when bad results happen with a too-high dose.

      Unfortunately, too many prescribers go by what pharma reps told them 10 years ago. Especially with Strattera. Way too high doses.

      It’s a hot mess. With all races and populations.

      From what I understand, yes, the risk of problems with CYP2D6 is likely higher with “Black Africans” (the term used by the studies) (0-19%), seemingly more than twice that of Caucasians (5-10%) and far higher than Asians (0-2%).

      There can never be definitive data on this, because Black people are not genetically monolithic. Neither are Caucasians or Asians.

      We should not deprive someone of a drug trial simply because they might be poor metabolizers, based on this notion of “race.”

      Overall, Strattera does not work that well for most people with ADHD, especially at the higher doses. I think Dr. Barkley said maybe 25% do well on Strattera.

      The high-level experts I respect suggest that Strattera at a low dose (e.g. 25 to 40 mg) can work well in combination with Concerta. I had also observed that before reading the medical clinical guides.

      I hope this clarifies.

      Gina

  6. Thank you so much for this informative series! I have gotten so little information from doctors. I actually got genetic testing done and found that I had a gene for fast metabolism of stimulants. My doctor told me that only guanifacine was recommended, but that made me sleep all day. Another doctor tried straterra but it was like taking a sugar pill.

    I finally found a doctor willing to try vyvanse despite my genes and now I have a new definition of the adhd rollercoaster – I take it at 8am, feel calm and collected and get so much done, then noon hits and I’m extremely tired and depressed. My doctor is willing to dose twice a day, but knowing what you do about fast metabolizers (my doctor, despite many years of experience, has never seen this), would this be unhealthy for me? I’m unclear on whether the fast metabolizing of stimulants just makes it harder for them to stay in my system or if it means stimulants are actively harmful for me. I would appreciate any insights, and thanks again for writing this!

    1. Hi Kat,

      Thanks for writing. We are thrilled that our series was helpful to you.

      It was a BEAR to write. And I’m sure it could use more tweaking.

      But at least it helped you to understand that being a rapid metabolizer for stimulants DOES NOT MEAN YOU CANNOT TAKE THEM.

      Stimulants are the first-line medication for ADHD. And if the physician won’t prescribe them, there needs to be a VALID reason.

      Misinterpreting genetic testing is not a valid reason.

      Being a rapid metabolizer means exactly what you have described: A medication that lasts about 8-12 hours for “normal” metabolizers might last much less than that for you. By contrast, slow metabolizers might feel the medication’s effects for much longer than 12 hours.

      There is nothing wrong with this. There is nothing wrong or harmful about taking 2 doses daily of a “long-acting” medication. If that’s what it takes to consistently treat ADHD symptoms throughout the day.

      If you are carefully monitoring your symptoms and you can tell when the first dose is wearing off—about 4 hours later—that is a perfect example of how being a rapid metabolizer works.

      Here are two caveats:

      1. You do NOT want to take stimulants in order to super-human propel yourself throughout the day. You also need supportive strategies (using a calendar, a ranked list of priorities, etc.)

      2. You DO need to get sufficient sleep.

      I hope this helps.

      g

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

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

    1. HI Jennifer,

      Another reader offers this information:

      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.
      ——-

      I hope that helps.
      Gina

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

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