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Intuniv Answers: ADHD Neurotransmitters – Glutamate Matters
Intuniv For ADHD: Details Beyond ADHD Indications
August 22, 2010Urinary Neurotransmitters Measured
August 31, 2010
Connections Matter – Wikipedia
Intuniv, Glutamate and ADHD Symptoms
Thanks to Intuniv we have a new neurotransmitter to consider – and it must be considered in the context, as with any other ADHD med, of the Therapeutic Window. Glutamate, as you will soon see in these pages, as well as several others [PEA, Dopamine, Norepinephrine, and indeed Serotonin] can all make a difference as we regularly address the specifics of ADHD neurotransmitter corrections. For this post: specific glutamate considerations.
For The Record
These are previous CorePsych Blog posts on Intuniv:
- – Intuniv Overview This is the first post on the details and pharmacology
- – Intuniv Dosing Details This post deals with precise dosing strategies
- – Drug Interactions With Intuniv Possible drug interactions documented
- – Intuniv and Addiction Indications A non-stimulant works in recovery
- – Metabolic Challenges Using Intuniv Understanding metabolic challenges helps
- – Intuniv Details Beyond ADHD Indications The literature covers other possible indications
Details About Glutamate
Amy Arnsten, PhD at Yale: See this summary page for details of this interesting ADHD science. This paragraph is from that page:
Goldman-Rakic used a spatial working memory paradigm to uncover the neural basis of working memory abilities, and found that representational knowledge is encoded by networks of prefrontal cortical (PFC) pyramidal cells with shared stimulus properties, engaged in recurrent excitation. [ed note: good working memory diminishes the possibility of ADHD.]
These recurrent excitatory connections depend on glutamate actions at NMDA receptors. Spatial tuning is heightened through GABAergic, inhibitory connections between networks with dissimilar spatial properties (e.g. Rao et al, J. Neurosci 20: 485, 2000). The working memory abilities of the PFC are also highly dependent on the neuromodulatory environment, whereby loss of catecholamines in PFC is as detrimental as destruction of the PFC itself (Brozoski et al, Science 205: 929 1979).
Another reference:
Russell VA, Wiggins TM, Increased Glutamate-Stimulated Norepinephrine Release from Prefrontal Cortex Slices of Spontaneously Hypertensive Rats Metabolic Brain Disease 25: 297, 2010
Bottom line in the office:
1. Excess glutamate alone presents as ADHD with hyperactive and significant ODD symptoms.
2. Diminished glutamate often presents as inattentive, and may be associated with ODD symptoms, but less overt anger.
3. Excess glutamate with both excess dopamine and norepinephrine appears as untreatable with any ADHD meds, even though symptomatically presenting as ADHD. The characteristic refractory, paradoxical response to stimulant meds, and to Intuniv often leads to the diagnosis of bipolar – but the dysregulation is in the neurotransmitters, not the appearances.
4. Number 3 is always associated with other biomedical issues including food sensitivities measured, e.g., by IgG – such as gluten sensitivity.
5. Measure when in question. Why spend more time guessing?
Still don't get the relevance? Take a look at this video on Dopamine and Glutamate-
Remember, this video is a patent oversimplification – dopamine does modulate glutamate, as does norepinephrine, but the interplay with many other neurotransmitters is not addressed in this short clip.
Stay tuned for more on the ADHD Neurotransmitter details – and sign up for email notifications for CorePsych Blog in the upper right hand corner of this post.
cp
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31 Comments
Hi Dr. Parker,
I am a 20 year old guy from Norway and I have struggled with ADD(inattentive type) all my life and I got the diagnose a month ago. I started with Ritalin (LA) at 20 mg, and I have increased the dose every week by 20mg. Unfortunatly it does not work for me at all and I am starting to get deppressed about it.
There is one thing I have to mention to you and that is that I have tried amhpetamin before. I have as I mentioned always struggled with focus and concentration problems and one day i was downdown drinking. A friend of mine proposed for me to try amphetamine/speed( the street drug). And I was so stupid that I said yes. We tried it that night and i noticed the difference of my cognitive behaviour. In total I have tried it three times including the first time.
My final question is: Do you think my stupid actions of taking the amphetamine-street drug has made me tolerant to any legal dosage of ADHD medicaton? Even methylphenidate?
I will be gratefull for any answers, Thank you
Aleksander
Aleksander,
We’ve seen many who try street AMP and discover that it can work well. I never recommend it, don’t endorse it, but accept that experience as a confirmation that the liver enzyme system CYP 450 2D6 is working very well – and that an AMP managed carefully might prove more useful than a MPH product.
Short answer: not a problem, but get with a doctor for precise monitoring and skip the Amphetamine play. Playing with it is potentially harmful because abuse can lead to depression and addiction.
cp
Hello again Dr. Parker,
Thank you so much for the quick response you gave me. However, I do not know if I got it all straighten up. You see I did not understand exactly of what you meant.
Let me please ask you again,
First of all, do you think my use of street AMP has given me a much higher tollerance for the AMP or MPH i get from the doctor? And if not, what can be the cause of why the Ritalin LA does not work? By the way I have checked my body if there is any products/things I am alergic to and the testresult was negative, which means that I am not allergic to anything acording to that test.
By the way, I know I am not supposed to use street drugs and it is a half year ago since I did it. But I am so afraid that it has made me tollerant/immune to the highest dosage available I can get prescripted by the doc.
You do not know how gratefull I am that you are helping people like me with all the detailed knowledge you provide. I hope you will discover and write more in the future.
By the way, dont forget to answer the questions 🙂
Thank you!
Best regards, Aleksander
Aleksander,
Sorry, got a bit carried away w all the other variables.
Short and sweet answer: No, not a problem w the street amphetamines causing tolerance or intolerance. The tests you ran were likely IgE tests not IgG – the IgG Qualitative test for specific foods is the best test for immunity issues – generally. See the links in this pdf: http://corepsych.com/tests14 – second page under IgG. You are much more likely “immune” because you are food Immune – not street amphetamine immune! 😉
Do take a look at my videos on Mind and Gut at http://youtube.com/drcharlesparker – they will give you much more of an explanation.
Then when you get a minute sign up here for this series of webinars: http://corepsych.com/totallyadd – free and going right to the mark. This is a recording of the first one we did last Wed night: http://totallyadd.com/webinar-archives/
Best!
cp
Thank you, I will get it tested!
I hope i not bother you with questions but I was wondering if you have any experience by using the aminoacid L-Tyrosine as a supplement. I have heard it is an important aminoacid for dopamine. And what about Acetyl-l-Carnitine for memory?
I hope you dont feel like you’re being invaded by all these questions, but you are the most knowledgeable I can think of within this particular subject.
Thank you!
Best regards,
Aleksander
Aleksander,
Both of those supplements can work, but I simply don’t recommend supplements without knowing what I’m talking about. I’ve often seen individuals who have excess dopamine for example, and the reason meds don’t work right is the dopamine is too much in the first place. See the set of posts I’m doing now on the various Walsh Protocols for Depression here at CorePsych.
This is a quick summary: http://corepsych.com/walsh
Then take a look at this video to get more clearly into the changes taking place in mind-science: TotallyADD Why Webinar: http://www.corepsych.com/totallyadd-why-video
cp
Hello Dr,
How would one know if the ADHD that you suffered from was due to excess Glutamate? Aside from Strattera that affects NMDA receptors are there any other medications to reduce Glutamate?
I read an interesting article on type 1 diabetics – they suffer from depression frequently due to elevated glutamate – Ketamine was highly effective for them.
Alan
Alan,
Neuroscience testing and Walsh testing will help understand the imbalances. Glutamate is most frequently elevated with immunity issues making stimulant meds unpredictable. See this for Walsh testing: http://corepsych.com/walsh.
cp
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M,
likely even Intuniv wouldn’t work but he might be one of the few who has a + response to Strattera as it is purely noradrenergic – the one he’s low on.
it’s worth a shot.
But more importantly, for the long term, he should have IgG testing, SEARCH it here, and get his diet squared away.
cp
My son is a 4th grader. He was diagnosed with a couple different types of AD(H)D (Amen types: Ring of Fire/Overfocused and Inattentive). He had/has the anger/frustration/crying/difficulty keeping up/oppositional behavior/OCDish tendencies which still comes and goes and primarily inattentive type of symptoms. He was put on Strattera 2 1/2 years ago (and nothing else). He is struggling in school and needs constant coaxing to stay on task/start a task/etc. Homework is a struggle nightly. I’m currently reading your (Kindle edition) ADHD Medication Rules (and we have an appointment to see you in Oct. I’m trying to move the appointment up (if/when you have a cancel)). My son seems so much like your Thinking/Indecisive type. (although I haven’t finished the book yet). Wondering if we should struggle with the school issues and behavior or ask his pediatrician for a “trial” (sorry) of intuniv to assist with getting him through until we see you. Any assistance would be welcome. Thanks.
Tracy,
Way to much time has passed from this comment/question for this reply to be of much value, and, with all I do in these notes and meetings, I’m just not good at names… so we may have spoken about these issues already. Bottom line: this is a great question for readers anyway, so will throw a note here into the fray:
First point: I will, with this reminder note from you regarding Intuniv challenges, pull together a blog post on *Rules for Choosing Intuniv* and *What To Do When Intuniv Doesn’t Work* [as “predicted.”]
Yes he is an excellent candidate for Intuniv with the following precautions:
1. He has been evaluated for slowed metabolism and elemental slowed metabolism is off the stove. [See Transit Time on CorePsych Blog Search]
2. He has had neurotransmitter testing and his glutamate is not elevated.
3. He is not a picky eater, and does comply with a protein breakfast.
4. He has failed Intuniv at a very low trial dose [.5 mg].
These are a few quick reasons to not give Intuniv a try – stay tuned for those blog posts.
cp
Guest:
Tricare covers IgG testing thru NeuroScience labs. The links are over at http://www.corepsychblog.com/neuroscience – The problems arise with inexperienced interpretations – those results are significantly helpful, but only place in context of the multiples of bowel function, liver detox, appropriate supplements, etc.
cp
T,
This is a link with specific refs and if you need some more go to celiac.com or gluten.com
http://parkerschlichterandassociates.com/wp-content/uploads/2010/04/Understanding-IgG4-Food-Sensitivities.pdf
It’s a hard call on the psych side, often if we do a long distance Skype consult we can send a note to an understanding GP and they will go for the review. Also we do IgG reviews all day and are accustomed to helping you with that one if you wish.
cp
Definately wish to do the IgG testing but suspect I would have to pay out of pocket if I can’t get one of my providers to order it (though I can try). Do you know approx price?
Or, do you have any idea if you can order it and I can get Tricare to cover it? I think they typically cover only if ordered by a tricare provider and / or PCM. Not certain on that though, I may have to call them.
Do you have any idea on this?
Anno,
I know you don’t know this about me, but I am a stickler for ‘never’ saying ‘never’, and ‘never’ using ‘always’ 😉 These findings are very frequently found with immune dysregulation but not always – could be related to med dosage etc.
If gluten sensitive, then you can appreciate the strong possibility that he is also allergic to another product, not yet measured or on the medical radar…. like my frequent intruder: milk. So many are stuck on the gluten subject and miss the other possible allergies that can also have significant downstream consequences – also with the various NTs out of whack as you describe. You may enjoy this CinchCast on this topic: http://icin.ch/4U2Tc
More testing strongly suggested –
cp
We recently discovered my 13 year old son has high glutamate, GABA, dopamine and norepinephrine, and slightly low seratonin. The Celexa and Cymbalta he took briefly brought on suicidal thoughts, worsening of his depression and anxiety. Once he stopped them he was back to being merely anxious and depressed. We started some herbal remedies which also brought back the same bad side effects – so we are stopping them and looking for other ideas. He is gluten intolerant, and the past year or two started sneaking gluten. He’s been pretty clean about gluten the last few months trying to heal.
We’re stumped trying to figure out what to do next – I was intrigued with the statement that people with high gluatmate, dopamine and norepinephrine always have biochemical issues like food intolerances – how would you address this?
Thank you!
What happened to all of your interesting questions and comments?
I’ve been using this Disqus [for “Discuss!”] and am trying to find the best way to keep on top of postings with this software. Seems like I am almost there with understanding just how to use if!
cp
CAN ADULTS TAKE INTUNIV FOR ADHD
Hello Dr. Parker,
Four months ago we added our first child to the family. Prior to the addition of a child, a friend lent me the book “Driven to Distraction”. Well, I found myself in that book and have since been diagnosed with ADHD (PI, but there are certainly hyperactive and impulsive components). The diagnosis and treatment was one of the best things that ever happened to me. I’m a better husband, father, and doctor. I actually like my job, as opposed to before continuously thinking that I should have become an engineer or something (I hyper focus really well, which got me through all the years of school). I don’t lose things all the time, I’m not nearly as upset by the constant interruptions that go along with my job and family, I’m not nearly as restless, I’m more present and don’t feel like I am somewhere else, I respond more quickly to my techs and coworkers and have the ability to attend to more than one issue at a time, and I feel like I can actually take care of my wonderful daughter . This, as opposed to prior, when I wondered if it was really a good idea to have a child considering I felt like I had so much difficulty managing my own life. I did not want to be my “never there” father (who I actually understand much better now, considering the road treatment has brought me down and knowledge of the fact that “apple never falls far from the tree”).
I was started on just Wellbutrin. Starting with the first dose I felt like the stuff was the best thing since sliced cheese. Even though slightly euphoric and with a tingly feeling (those things went away after a few weeks), I had never been able to focus so well, had that kind of working memory, had so much patience, or been able to shift so easily from one task to another. I became less irritable, my wife and I had long and wonderful conversations we had not had for ages, I didn’t impulsively snap at her without hearing her point of view, I felt more empathy for my patients and was less likely to cut them off. My first doctor (I have since changed) suspected the effect was placebo. Perhaps she was right though I had a hard time with this hypothesis considering the initial effects this medication had on me were not even ones I recognize as being part of my ADHD (until I read they were, later on).
The only problem, was that I felt constipated. After a month, I either got use to this or it went away, I can’t remember at this point it feels so long ago (about 9 months ago). Another thing that went away was much of the focus that I felt initially. A feeling of contentedness remained but I began having trouble again.
Adding methylphenidate (first instant release, and now Concerta), brought all of those great effects back. The constipation issue seemed to slowly build from a tolerable level intolerable. We dropped the WB down to 150mg QD, which took some time getting used to (I had a hard time dropping the dose, because I really love the stuff and the effect it has). For about a week things seemed to go well then the constipation became an issue again. I’ve tried using a stimulant laxative (OUCH!), and polyethylene glycol (not ouch). The polyethylene glycol was somewhat effective but still did not work all that well. I felt as if nothing was moving in there – like everything came to a standstill, my stomach barely growled. Last week I was at the point of considering an appointment with my primary to discuss if it might be IBS rather than an issue with WB. I then decided I should stop the WB all together to see if this might help. I stopped 4 days ago (aside from a 150mg dose yesterday evening, when I couldn’t take the crazy wound up restlessness I felt – and within 30 minutes it was gone).
My innards feel great – my “IBS” and constipation are gone. The issue though, is that Concerta (currently using 28mg PO bid – AM and afternoon to extend the duration of its effect into the evening) works OK, but the combination is what really seems to make the difference for me in increasing clarity of thought, attentiveness, better working memory, focus, reduced distractability and irritability. I suspect some of the issue with craziness I have felt the last couple of days may be withdrawal from WB.
So, after all that, my questions are: Do you know of anything other than laxatives and more water (I already drink a lot during the day), to manage WB related constipation (I have been reading some of your posts regarding transport time and wondered if all this might be somehow related. I wish I had time to dig into this further but I just don’t – if you have a direction to point me in I am happy to read). Or, might it be worthwhile to consider another medication to supplement Concerta (or even replace Concerta, Vyvanse is not on my insurance formulary). Reading about Intuniv, I’m also wondering if you think that might be worth consideration (that is on the formulary)?
Sorry if this question is too long winded and likely in the wrong place in your blog. I considered just asking the question but thought some background might be of assistance in your answer. Also, I’m having computer issues and have lost patience in looking for “the right place” to put this comment.
Thank you
Tony,
Several issues:
1. Easy first level for constipation: Vit C, buffered to tolerance works as great clearance and shows no evidence of other problems. Mag Glycinate [chelated] and Omega 3 FA in the 2-3 Gm range could all be helpful, and can be used in combo.
2. Moving away from just treating symptoms [not my style] I would do the IgG testing mentioned in multiple places elsewhere, find out if there are underlying contributory problems and cover that one. I am so Sherlock on this I deftly noted that you mentioned cheese!
3. Sounds like you are doing a good job of dialing it in effectively with your doc.
4. Sometimes a change to AMP might help, but absolutely no guarantees.
cp
Dear Dr. Parker,
An update. Though I feel like I’m most certainly doing
better than I was when I wrote that initial note, I feel like things could be
better. Just a few questions if you don’t
mind:
1) GI issues: You NAILED this one. It seems the Wellbutrin
really just exacerbated problems I had had for years. I can remember having GI
issues since my early 20s (at least 12-13 years). Constipation was never really
a problem for me but I had also been exercising 4-6 days per week consistently for
at least the last 7-8 years, until the change in lifestyle brought about by
starting our family. Even after discontinuing WB the problems continued, though
not as badly. Titrated Vitamin C and Magnesium worked wonderfully, great
suggestion. Discussing IgG testing with my psych, he was skeptical and
preferred I see a GI doctor for further evaluation. To be honest, I was and am
also skeptical considering there is little literature that supports its
validity in diagnosing food sensitivity issues. But, I thought looking at the
idea of food issues was worth a try and during an elimination diet found that
removal of gluten and milk products SIGNIFICANTLY relieved my abdominal issues
and not only that – my mood and mental state is more consistent. But, I’m still
having issues off and on and never know if I accidentally ate some gluten or casein
product or if there is something else. Or is it just mysterious “IBS” triggered
by ????? Celiac blood testing was
negative (I had not been eating gluten for 4-6 weeks prior to the testing, so I
had a strong sense it would be). I have an appointment for endoscopy and
colonoscopy (FMHx of Crohn’s) in which I’ve been told to eat copious amounts of
gluten containing foods for two weeks prior. I’m reconsidering diagnosis, I
just don’t want to feel that way again and since the end result will be the
same (no gluten in my diet), I’m not sure “official” diagnosis is worth it.
It’s very confusing and frustrating – I’m now often looking
at each piece of food wondering if tomorrow I’m going to feel like crap if I
eat it. Since even your small suggestions
have been so helpful, I wish to at least try IgG testing – any suggestions on
convincing one of my providers to order it?
2) DOE: Currently
using Adderall, and it works well but I light the stuff on fire (I also did
that with methylphenidate, though with the WB on board it had a longer DOA –
burned 54 mg in 6h; Thyroid panel was normal). 10, 20, and 30mg have “holes”
between the 1st and 2nd releases. At 40-60 I function better and more consistently
(without ups and downs from the periods of ineffectiveness). At 60 I get 8
hours, and feel like I perform pretty solid. I have found that the holes are
pretty consistent, so since I am pretty much “on” all day, from work to home, I’ve
come up with the best solution I can to get the most of my day out if it – but it’s
a pain in the ass! Try being ADHD, being swamped with patients and remembering
to take that 9:30 dose because the 7:30 one is going to stop working in about
30 minutes. I take 20mg @ 7:30, then
10mg at 9:30 to cover one hour hole that comes at 10:00. This covers me until
around 2 (with some ups and downs b/c of the dose difference). I try to go as long as I can without it, taking the
last 30mg at around 3 – timing the ~30 minute hole to occur right around the
time it’s time to commute home (I “love” having withdrawal effects while
driving home, it’s so nice when it kicks
in again). I save the higher dose for the later part of the day because
honestly – I have more difficulty in my unstructured home life than I have in
my structured work life. Not a big fan of my wife getting on my case when the
hamburgers catch on fire! Or going to lala land while our toddler is playing
with power cords.
Long story short –
how do I convince my psych (will be changing soon) that it seems I need higher
than FDA recommended doses? When I last saw him, as far as he was concerned
I was topped out in dose he was unwilling to prescribe anymore. That is the
same reason he was unwilling to try a higher dose of Concerta. To me it seems
that if I’m only getting 8 hours at 60mg, it’s going to take around 80ish to
get me to the 10 hour DOA. I could probably finagle that to stretch it into the
full day but from what I can see you suggest an additional dose in the evening.
So it seems to me that at my burn rate I would need another 30-40IR to get me
through the evening – it just seems like a lot of Adderall! Suggestions? MPH
patch?? I do like Adderall better but a smoother ride every day would also be
nice.
3) Have you ever
consulted with any providers in Albuquerque or can you make any suggestions on
providers? Sadly (I really did get along with him, he was a super nice guy,
I kind of felt like we were learning together in some aspects) my doctor has
left and I will be getting a new doc in August sometime. Since there is no doc
right now I am going through a primary care manager for refills – but may be
able to get a referral to an outside tricare approved provider if I feel
changes need to be made.
Thanks for all you do!
T
Thanks for the information, may be useful to readers. I like your article, especially about neurotransmitters, Brain of GABA, Serotonin and Dopamine.
AnDg,
Thanks again for weighing in,
cp
I have figured out from your article that I have excess glutamate and excess dopamine and norepinephrine. I have tried concerta, straterra, wellbutrin, adderral. I was a zombie. I am now gluten and dairy free. I exercise. I am doing better. Any suggestions of what else I could do? I believe the term is sluggish cognitive tempo. Great web site. Thanks!!!
Gary,
Can’t be certain without more specific info, but it is highly likely that meds will work after you have been on the diet as you no longer will suffer from a bulletproof liver, and an insufficiency of neurotransmitters with a narrow therapeutic window. If the meds don’t work now, or if you add specific neurotransmitter precursors after measuring markers, then it’s likely that you haven’t completely covered food allergies, and removed all the offending antigens.
cp
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