ADHD Insights: CYP 450 2D6 Details Matter

ADHD Insights: Measuring Arsenic
September 21, 2012
ADHD Insights: Prozac, Paxil and Amphetamines
September 23, 2012

ADHD Medications Require More Careful Thinking

This brief video breaks down an essential difference between amphetamine [AMP] and methylphenidate [MPH] stimulants. In 4 min and 50 sec I break down the serious metabolic details for those important medication matters. Think: CYP 450 2D6.

I've discussed these interactions in hundreds of presentations since 1996 when I first discovered how these challenges impede metabolism and create significant ADHD Medication problems. It's encouraging to see that others in the genotyping community now support the measurement of these important variables.

AMP and MPH both have different pathways. AMP is a substrate of 2D6, while MPH blocks 2D6. AMPs are very significantly effected by some antidepressants – so one must pay careful attention.

More Details

You can also find even more details here in my [early discount] book New ADHD Medication Rules on this important metabolic subject. And watch for my next video on Prozac, Paxil and amphetamine stimulants, coming tomorrow. It shows specifically why CYP 250 2D6 is so important.


Please do drop a comment if you think this kind of information is helpful for your medical care. And like it  if you think your friends/colleagues should know about this important science.

Dr Charles Parker
Author: New ADHD Medication Rules – Brain Science & Common Sense
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Complimentary & New: 23 pg Special Report: Predictable Solutions For ADHD Medications


  1. CD says:

    I think I have this issue. Vyvanse works well at first but I have to take only 30mg or less and even then within a week I can feel it “building up” in my system and I become scattered and don’t sleep well and lower back starts hurting. Buildup also seems to happen if I take Wellbutrin XL but it takes a lot longer maybe months and then I’m getting very irritable “touchy” and mean. I can do relatively well on Evekeo but eventually (months?) I get the “energy drop” which come with a hurting lower back as well as it just not treating my symptoms as effectively. (Roving therapeutic window?) Wellbutrin helps this (and gives motivation) but only for so long before I have to stop taking it due to “touchy” effects. I cannot tolerate Prozac or Paxil even on their own (tried a long time ago) and Zoloft was only very minimally effective as a solo treatment so I thought I must not have comorbid depression but maybe it is exacerbated by the stims. Would you suggest adding an SSRI? And if so which? I have a lot of allergies which I try to address via paleo-ish diet and zero wheat/gluten/dairy which is what has made meds work even a little bit like they are expected to during the past ~3years that I have been eating that way. I supplement with high quality individual b-vitamins, magnesium and zinc, yet am still not achieving consistent long lasting treatment results. Do you have any suggestions? What about a liver detox how do I do that? I couldn’t find the info on your site. Thanks for all your posts they have really helped me in my journey to get to this point of at least some success!

    • CD,
      I don’t make recommendations without fully understanding the clinical picture, and even then often recommend testing. If you and your doctor assess depression an antidepressant is often indicated, one that is clean on 2D6.

  2. Sylvia trudeau says:

    Started with 20 mg of Trinellix and 36 mg of Concerta this morning. By noon, I feel really, really depressed. Should these pills betaken at the same time?

  3. Alison says:

    Wondering if there could be any interaction between Trintellix and Ashwaganda?


  4. Maria says:

    Hi Dr. Parker,

    I am new to your work, and find it fascinating and insightful. Thank you.

    In trying to understand the drug interactions with medication, I am wondering if you could answer a couple of questions for me.

    I have been taking adderall 10mg twice a day for my ADHD for years now. Recently my new therapist put me on wellbutrin sr 100 mg once a day for moderate depression. It is something I have been dealing with on and off for over 3 years now. It started with post partum depression, after birth of my first child.

    After reading your information on drug interaction, I am concerned about these 2 meds together. And it didn’t even concern her at all. She said she liked this one bc the fewest side effects, no weight gain, loss of libido, etc. With the doses being so low is there any chance for reactions? If so can you explain what they would be?

    Also, regarding the reactions with meds and antihistamines, I have been taking Benadryl at night to sleep for about a year. Does that mean I am at risk? How would this effect things with the wellbutrin? Which I haven’t started taking yet bc I wanted to know more about it first. And I’m glad I waited.

    Thank you. I am still trying to understand how all this works…

    • Marie,
      At lower doses these two meds often don’t “absolutely” cause problems, but the operational word for me is “can.” Informed is always better than uniformed. Wellbutrin is a ‘moderate inhibitor’ that can cause a buildup over time, especially w a person who suffers with a genetically polymorphic ‘small’ 2D6 pipeline.

      The side effect often builds up over time and presents as more angry, less focused, sleep problems etc… simply signs of too much stimulant. Benadryl reaction also depends on dose – with the same symptoms. You might take it for sleep but eventually, paradoxically, may find subtle trouble with sleeping.
      Thanks for your question,

      • Maria says:

        Thank you for your quick response. It is good information to have.

        I have one more question. Do you know why wellbutrin seem to cause hairloss? read a lot of posts of people with this problem. Is there anything to do that might prevent it? Supplements maybe?

        • Marie,
          Don’t have a firm easy answer on that one. Biotin may help, but more importantly: trace element and hormone testing for adrenal and thyroid would likely prove productive – beyond the TSH.

  5. Jennifer says:

    Does this apply to the new antidepressant Brintellix?

    • Jennifer:
      From: *Use of Brintellix in Known CYP2D6 Poor Metabolizers or in Patients Taking Strong CYP2D6 Inhibitors*
      The maximum recommended dose of Brintellix is 10 mg/day in known CYP2D6 poor metabolizers. Reduce the dose of Brintellix by one-half when patients are receiving a CYP2D6 strong inhibitor (e.g., bupropion, fluoxetine, paroxetine, or quinidine) concomitantly. The dose should be increased to the original level when the CYP2D6 inhibitor is discontinued. It’s a 2D6 Substrate.

  6. Locri says:

    This is a great explanation of CYP2D6. I’ve been struggling with understanding it as I think I have problems. Related to this, I have a few questions:
    1) Have you ever heard of joint pain and stiffness as a sign of medication build up due to 2D6 (in particular using Vyvanse)? That seems to be my main issue as it works fantastic otherwise, but can no longer use it due to this build up.
    2) I see that you mention both AMP and MPH as being blocks, but every reference I can find says that MPH is only a substrate, not an inhibitor. Is there something I’m missing regarding MPH?
    3) What do you think of the study that showed things like Ginkgo Biloba and Valerian can act as an inducer for 2D6? Could one possibly still use an AMP medication with one of these herbs to prevent blockage? (Link for reference:

    • Locri,
      Today I completely corrected this post, and added many other links to ensure that I communicated the blocking and substrate issues more effectively. MPH blocks 2D6.

      1. No haven’t heard of that problem secondary to MPH and 2D6.
      2. No, they don’t both block – and it’s not a substrate either see the link above.
      3. No, the standard of care does not encourage mixing known drug interactions to correct other interactions.


  7. Jessica says:

    I came across one of your youtube videos while googling insomnia and Vyvanse. I’ve gone through some of your videos and I’m trying to find some answers, as to why I have such a hard time sleeping, while taking my 40 mg Vyvanse (i take it at about 8am and it starts working within 20 minutes). This is the 3rd ADHD medication my psychiatrist has put me on, because the others increased my anxiety too much and made it difficult to sleep. Vyvanse, has by far been the best medication I’ve been on, but I’m still having a hard time sleeping. My psychiatrist requested I start taking melatonin to help and continually increase the dosage until I started to sleep. It never did work and so he then mentioned prescribing sleeping pills, but I’m not interested in that. I don’t want to take any more prescription medication. When I try to go to sleep, I feel like the medication is probably still in my system and I feel a little anxious. The only thing that can help me sleep is if I take my alprazolam .5 mg and I really don’t even like doing that. I slept just fine before adhd medication and I would love to get back to that. I’ve tried many things to try and help, such as, exercising more, different teas, valerian, ashwagandha and even a magnesium oil. I was wondering what your thoughts were on this and if you had any advice for me.

    • Jessica,
      Yours is a classic metabolic issue, subtle but nevertheless part of the challenge. When a person has a good relationship with their doc, is asking all the right questions, and remains puzzled with the symptoms you present, it’s most likely that you have a slowing of liver metabolic rate w/o a “liver problem.” Meaning your Liver Function Tests will prove likely terrific – but the problem remains. Easy first step: do the Two Step Liver Detox, hitting phase 2 first, then phase 1&2 about two weeks later. Specific supplements should help out… unless you have significant additional challenges, – most likely on the immunity front, that preclude that successful detox outcome. Take a look at this download and let us know if your TT is troubled!? – call Desiree at Services if you have any questions she’s been thru this process a few times with a variety of folks. Or you can schedule a Brief Chat at Services.

  8. Charlotte says:

    I am so confused! Should my son be taking ADHD meds combined with Prozac or not? He is homozygous MTHFR C677T so he takes b12 & 400mcg methylfolate and is gluten, dairy, soy and egg free. Has been on 10mg prozac for over a year. Worked great at first but now he is moody and sensitive. Just got off concerta and starting slow with 5mg focalin in am and half tab focalin in afternoon, and continuing 10mg prozac. Focus somewhat improved, still moody, sensitive and impulsive.Could the prozac be causing more harm than good?

    Homozygous – MTHFR C677T, CYP1B1 L432V, NAT2 K268R, MAO-A R297R
    Heterozygous – CYP2D6 2850C>T, CYP2E1*1B 9896C>G, CYP2D6 S486T, CYP1B1 R48G, NAT2 I114T, COMT V158M, COMT H62H, VDR Bsm, VDR Taq, AHCY-01, AHCY-19

    • Charlotte,
      Best to not combine either MPH or AMP products w Prozac, as it can, even after 6 mo, begin to accumulate/interact in counterproductive ways- I would talk to your doc about alternatives to Prozac and expect resolution of problems to take about a week for detox. The other polymorphisms are not relevant to this particular issue as is the interaction with the Prozac.

  9. Tonia says:

    I actually thought the zoloft was blocking the adhd medicine all along for my 10 year old,….but what do i do the adderall works for adhd, but he gets weepy and emotional when we remove the zoloft….i cant find about taking the zoloft 3 days a week?
    We live in charlotte and our pediatric psych gives both to us…

    • Tonia,
      Can’t tell you specifically what-to-do w/o a full review. But an important general rule regarding your current struggle: Let go – absolutely not a problem for 10 yo unless the dose is wrong or side effects occur. My regular routine: use both meds together w your docs approval – that is the standard of care. Every other day creates significant problems w discontinuation, ups and downs, mood swings etc as Zoloft is ~ a 24 hr half life med. Type “seesaw” into CorePsych SEARCH and then see multiple videos on ADHD Med Dosing at channel.

  10. […] Tomographic Views with SPECT brain imaging provide considerable diagnostic assistance for NPH diagnosis. Without SPECT he would remain almost completely untreatable, and psychiatric meds would fail to render the improvement he sought.  His treatment with 40 mg of Prozac, blocking CYP 2D6 and 3A4 often contributes to a dementia-like state, as I’ve reported elsewhere here at CorePsych and on YouTube. […]

  11. C. Baker says:

    We have significant trouble finding psych meds or homeopathics that help our7 year old daughter. Her OT keeps saying she has trouble metabolizing medicines, but our psychiatrist hasn’t ever said anything like that. (We are on med # 8 now and have been at this for over a year). We live in the Atlanta area….do you know of any Drs in our part of the country that include metabolic issues as part of the treatment approach? Maybe this is our missing link!

    • C,
      We do consults everyday globally, so wherever you are will not be a problem. I completely agree with the OT, as I on another comment you provided more Roving Therapeutic Window insights. [Download Transit Time in the Video Description] See and we can do anything from a Brief Chat, to a full on metabolic review – either long distance or in the office if you want me to write for the meds – all outlined in detail on the /services page.

  12. kami allred says:

    Help ive been taking adderall ir and prozac and latley I feelltired and crazy! What can I do?

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