- To Change Your Mind - Details Matter
Intuniv For ADHD: Details Beyond ADHD Indications
ADHD, Immunity and Gut: Picky Eaters Revisited
August 15, 2010Intuniv Answers: ADHD Neurotransmitters – Glutamate Matters
August 29, 2010
Sharp Eyes - Johan J.Ingles-Le Nobel via Flickr
Intuniv for ADHD Sets the Stage For Improved Attention Inquiry
Our multiple CorePsych Blog reports on Intuniv [this the 6th] have kept CorePsych Blog on the first page of Google for many weeks [today #9 on the first page of 199,000 hits], … and why? Hey, I'm not bragging, I'm thanking… Google first page is a direct result of the excellent and informed questions from our thousands of CorePsych Blog readers out there – you readers have been looking for answers to the complexity of ADHD Appearances. Thank you for over 469 comments and questions!
– Yes, you read that right, we are collectively suffering from a National ADHD Myopia – short-sighted, anachronistic perceptions, treating vapors and impressions, needing immediate Big Vision correction. And don' t plan on the new DSM 5 to help you out – it only reshuffles the Go Fish cards already on the clinical table. Just like our friend the owl, we can't hit the target if we can't see it. Sharp inquiries bring more definitive targets. New eyes are required.
Too Many Are Having Big Trouble Using ADHD Appearances
Diagnostic imprecision is rampant throughout the land [has been for years], and, for those finger-pointing ADHD ranters thinking ADHD is a belief system: you'll be disappointed, there's no one to blame for this imprecision. We simply have not caught up with the functional brain science [detailed in my new book: Rules] – and almost no one is paying attention to the nuances of multiple molecular and cellular imbalances. The ranters, including Tom Cruise [from my first post ~ 4 yrs ago], are, in point of this fact, somewhat correct: we direct our treatments by appearances, not the underlying science.
Intuniv Staging for Deeper ADHD Inquiry
At first blush it appeared that adding Intuniv to our ADHD pharmacopoeia would solve a number of problems – most especially the problem of associated anger with ADHD – and, for many it has indeed added significant treatment benefits, as documented in those previous CorePsych postings. The interesting and unexpected outcome, however, appears to be of greater interest – what about the many who didn't improve? What about those that deteriorated? The many questions beg for better answers: just exactly what is ADHD, and, what is not? Even more to the point: what are ADHD spectrum disorders on a neurophysiologic level?
The inarguable benefit that Intuniv has delivered to the inquiry, to the ADHD birthing table, is a number of new, unanswered questions, and helpful new extrasynaptic activities that begin to address the extensive underlying biology of ADHD. Many of these abundant questions have previously only been resolved by throwing atypical antipsychotics at mood disordered individuals who suffer with a dual diagnosis of ADHD.
The Glutamate Tipping Point
As noted previously: Intuniv, the glutamate agonist, can helpfully increase glutamate, a neurotransmitter that specifically effects both cognitive and affective centers in the prefrontal cortex associated with working memory- but what if the glutamate is already high for other reasons? What if the ADHD symptoms are associated with/a result of an upstream abundance of glutamate? The unhappy end result of using Intuniv under this circumstance is relative Glutamate Toxicity. In the office, and frequently seen in many of the Intuniv questions here at CorePsych Blog: glutamate toxicity results in marked emotional deterioration, rage, even appearances of semi-psychotic behavior. – This phenomenon is not the rule, but is sufficiently common that we should have it on our thoughtful, sharp eyes radar.
For this reason, especially with refractory individuals, we measure [among 11 other neurotransmitters] glutamate levels, – and we do see glutamate increased in those individuals with significant immune disorders that present comorbidly with those ADHD Appearances. And, yes, Intuniv does not work well for those with elevated urinary glutamate – regardless of your take on the neurotransmitter science. [This observation is replicated regularly, and encourages improved appreciation of more routine neurotransmitter testing.]
Now, after these brief days of Intuniv practice, we have even more new science, new inquiries, new neurotransmitters to talk about. We're beyond dopamine and norepinephrine as the only neurotransmitter relevant for ADHD treatment. Now we know that glutamate imbalances can provide ADHD Appearances through excess glutamate. These many mechanisms of excess glutamate vary, but are increasingly understood as associated with changes in glutamate decarboxylase, the enzyme that breaks it down.
Beyond Appearances: Deep Dive Into Immunity and Amino Acid Neurophysiology
For those who want to dive deeply – more into the science take a look at one of these 50 papers on the relevance of Glutamate Neurotoxicity – this one appears as a report of considerable interest:
–Matthews CC, Zielke HR, Fishman PS, Remington MP, Bowen TG: Glutamate decarboxylase protects neurons against excitotoxic injury. J Neurosci Res; 2007 Mar;85(4):855-9
Academia Is Not Translating The Science For Clinical Application
Yes, the platitude folks are still thinking the Sun revolves around the Earth, as they are deeply embedded in beliefs and ADHD Appearances, not science. Gina Pera, ADHD maven and author of Is It You, Me or Adult ADD? recently re-experienced this dilemma with no less an august facility than Stanford as they discussed the indications for stimulant medications from what appears as an antiscientific, gossip-oriented perspective.
Stay tuned for more on neurotransmitter information –
cp
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20 Comments
So if I read the article correct- kids with immune system issues that have high glutamate levels would not benefit from Intuniv? Our ten year old has a big problem with casien and minor with gluten. He has anxiety and ADD. Also very aggressive and explosive when we impose our will for one thing or another. We are on Intuniv 3mg new this week. 2mg wasn’t doing it. We thought it was working for a minute there at first but doesn’t seem to now. It’s hard to tell he has good weeks and bad weeks as far as explosive behavior, which is the most problematic symptom we deal with. ughhh. We had temporarily switched to guanfacine for a few weeks he ended up having a panic attack and major anxiety, so now we are back to Intuniv. WE also stopped doing the GFCF diet because we thought it wasn’t really doing anything to help with behavior and thought it was tough to do to be honest so we let up on it lately. That being said we only allow casein here or there like letting him buy school lunch on Fridays (which he wants pizza). Should he not take something that increases his glutamate even though it seems to help with the anxiety? Could it be helping anxiety but making aggression and anger worse? Is that possible? The doctor wants to see how this goes and then maybe add a very small amount of stimulant b/c his brain mapping stated he could benefit from a stimulant. I know we should probably get back to fixing his diet and making sure to have him take his vitamins/minerals again. But none of it seems to work that noticeably, not even the meds. We started this process almost a year ago and feel like we are still at square one. Whats weird is when he is sick, hes a lunatic! Like this weekend, hes got a virus and his brain is making him VERY aggressive and combative much more faster than usual. We had originally thought a few years back and were told he had PANDAS. It’s hard to know what the heck to do to help him. Should he have more tests run? He’s had neurotransmitter test, food allergy, brain mapping. Came back low protein, high peptides. All we know is he shouldn’t have Gluten or Casein and that didn’t seem to fix anything really. If he felt even a little better it was hard to know. He certainly didn’t say and we asked him. Should we just keep doing this 3 mg of Intuniv? We are also setting up family therapy to deal with anger outbursts . What else should we be looking at here?
Dee,
The short answer, from my frequently witnessed office perspective – and without seeing the specific numbers [which always makes a difference – facts do count!] – is that he should absolutely stay off the pizza, and be absolutely firm on the diet.
I just had a super ~10 yo girl come back in the office yesterday, mother is an MD [OB-GYN] father a businessman, and we got their delightful girl completely straight on a variety of issues, including wetting accidents during the day at school – terribly embarrassing – by carefully measuring and correcting the diet – milk was the main offending antigen, and, naturally, she loves it. Yesterday, just as we were leaving with good reports across the board mom asks: “…btw, she has been wetting again at night and is worried about having the prob at summer camp, what do we do?”
My simple question: Is she off the diet? Mom’s answer, supported by dad, she does like her milk so much! – and has been drinking it for a treat on Fridays – and likely other days since parents have let up on what previously worked so well.
My rec for your guy. Do get him accurately tested to R/O whatever else, other antigen, could be causing the problem, absolutely. Then stick to it. PANDAS should be eval as a possibility, yes, as should candida. What allergy testing – did he have IgG? What mapping did he have – qEEG? What were the results of the NT testing? All of these should be reviewed explicitly and are details beyond the scope of these comments – as the entire picture needs not only a review, but intervention strategies that combine all fronts.
The answers are there, they just need a bit more teasing out.
cp
My question may not make sense as I am new as well to all of this. I have a 10 year old son brief hx 3 months premature , he was vent dependant and for the first few years had many resp issues. He was delayed but I was always told by K he would be caught up , so therapy after therapy we did as well as early intervention, he displayed OCD issues as early as 2 yrs old by 4 hyperactivity, 4-5 increased aggresion ( lots of changes a divorce, school not handling the noise of siblings, not handling school at all eating in office cafeteria to noisy etc) Of course due to family adhd hx ( my brothers) stimulants started. He was later dx Autism spectrum high functioning or Aspergers with ADHD, and now ODD. As well as anxiety d/o. He has been hospitalized twice. Intuniv was my last help seroquel put him in a majot hyper manicy state. Depakote he wouldnt interact or communicate at all and he is verbal, but doersnt express or communicate emotions well. Now he is off all stimulants first time in 5 yrs , I beleive was increasing his aggression, we just passed the 4 week Intuniv mark and fatigue fog is lifting , he is more like himself, we are still on Abilify as we have d/c it before and he does better with. In kids w/ ASD there gluthathione levels are usually decreased is this why the Intuniv works for my guy? DOes this meanit will continue to work and we are on the right path. I have tried diests as well IGFCF didn’t help although just casien free seems to alievate some issues as well as minimizing sugars and dyes. I do give Omega 3 and am starting some other supplements as well as alpha lipoic acid. My sone is way behind academically IQ testing inconclusive d/t lack of cooperation and his behavior impeding his learning. They also beleive he is dyslexic. Am I on the right track? Stimulants are done here I don’t want to ever put him on all thoise meds again.
Misty
Misty-
Interestingly at the last DAN conf I was quite amazed at the excellence of the science there, and yet the complete oversight regarding testing with NeuroScience for neurotransmitter levels. The debate about applicability is lead by studies, and many are simply not listening to informed patient care results.
RE: “In kids w/ ASD there glutathione levels are usually decreased is this why the Intuniv works for my guy?” You are likely mixing up glutamate with glutathione – two different topics. Glutamate is the Intuniv target [secondary through that post synaptic receptor], – glutathione is an antioxidant, essential for multiple functions including detoxification.
Your excellent efforts are covering a serious and useful waterfront, but those neurotransmitters are imbalanced, as evidenced by results, and he needs significant testing for specific immune dysregulation. I’ll wager is histamine is out the roof.
You are clearly well informed, on the right track, but need to get out the magnifying glass to better identify specific treatment targets.
cp
Dr. Parker: I don’t know where to begin, so I’ll start with my bottom line question. Do you know of any docs in your field in Arizona who are thinking along the same lines as you? My 9 year old son has been on nearly all ADHD meds for the past 3 years. None have worked for very long. Most of the time they work great for 2 weeks and then nothing. So we increase the dose, may or may not see improvement (doesn’t last), then he becomes grumpy and impossible to be with. He is a picky eater – loves carbs, won’t try anything new. He has sensory issues – i.e. he’ll eat a hamburger but won’t have any other preparation of beef/chicken/etc. We’ve been seeing a Dev. Pediatrician who diagnosed him with ADHD, but my son couldn’t finish any of the tests when he was 6 so any other tests they did with him can’t be considered conclusive. He has extreme learning difficulties, has an IEP, doing 1st grade work in the 3rd grade, everyone who works with him says he is very smart. A previous school did an eval when he was 6 and thought he may be on the autism spectrum. Back then, I tried the GSCF diet for 26 painful days. I saw little improvement if any. When you want to see improvement, any remotely new positive behavior is seen as “it’s working!” He is also chronically constipated – as few as 8 BMs a month. His regular ped has him on Miralax daily now to allow his body to “relearn” how to poop. His current med mix is Intuniv 2mg + Concerta 27 mg. At the beginning of the school year 8/9/10 he was on Intuniv 3mg and he was lethargic. We reduced the Intuniv to 2 mg, waited a few weeks to see what that would do…he still cannot concentrate. He also was on Prozac 20 mg, but has been off that for a month or more. We’re seeing slightly better days with the current med mix, but I have much higher expectations than what I’m seeing. Should I take him to a psychologist or a psychiatrist? His developmental ped says neurotransmitter testing is too new and isn’t conclusive. And IgG testing…she says I should just do the diet. He won’t eat that crumby GSCF food, neither would I. What should I do? p.s. I bought your ADHD Rules book and read it already.
Jody,
The psychologist that says neurotransmitter [NT} testing is too new and inconclusive is operating on gossip, not on experience. Nothing is perfect, NT testing is a form of biomarker assessment, – but having said that she needs to become more familiar with the literature, and not comment on what she don’t know, unless to simply say: “I don’t know.” Suggestion: Download the first pdf document at the top on the Neuroscience page here at CorePsych Blog and share it with your naysayer – peer reviewed evidence may turn on a light in that darkened room.
Another serious expert who often comments about evidence, specifically SPECT brain function evidence that he doesn’t know about, is Joe Biederman MD, acclaimed Child Psychiatrist at Harvard. Biederman weaves SPECT and neuroimaging into roughly 3/4 of his presentation as a means of substantiating material for ADHD prefrontal cortical impairments – then closes saying it’s snake oil when he has absolutely no idea how to work with imaging in his practice, and has never used the process with patients. I’ll bet Biederman has no use for NT testing either, because he simply has no experience with it. If you use NT testing, if you use SPECT imaging evidence your eyes open to many more possibilities. Psychiatry and mind medicine often remains stuck in beliefs, as real evidence is just too hard to learn, and one has to work extra hard to connect with that information.
This is the way change takes place – some take the risk and effort to understand that new process and some remain on the factory line assembling information based on cookie cutter perceptions. I hesitated to use this brain and body information myself, simply because I didn’t get it – so I am speaking from experience.
The current BM situation is bad, and often some [for a child start with two] magnesium chelated supplements in the AM or PM will prove helpful. First do transit time with a meal of about 1/2 can of corn and mark when he eats it, then watch his stools, or have him report when that corn comes through – should be 18-24 hr, [will likely be > 48 even with Miralax] I just had a very cool woman in the office yesterday, trim, not looking metabolic – “healthy” and good energy, but refractory response to psych meds for years – her transit time: Mon nite to Thurs PM. If the magnesium doesn’t work, don’t despair, he really needs more conclusive IgG testing to ferret out specific antigens – more evidence. She simply doesn’t know about that IgG point either, as just shotgunning diet may not help with a mysterious problem, for example, with eggs. If she were right the problem would be already resolved.
Prozac was absolutely contraindicated, glad you stopped that – drug interactions with Prozac abound – both with Concerta and with Intuniv.
If things remain stuck I can consult long distance, do it all the time, can send the testing out there and work to help your medical team with next steps. We see people from all around the country. And if you want me to write for meds, just fly into Norfolk would be the ticket, – arranged thru Sarah on the Services page here.
Thanks, I hope Rules was helpful!
cp
I confess to being a regular lurker/visitor to this site for over a year now. I am grappling with whether we should be pursuing further testing for my middle son, age 10. By age 2-3, he showed developmental delays in expressive & receptive speech. He received private OT & Speech Therapy (later supplemented by school IEP services) from ages 3-6 (speech only since age 6). He exhibited motor & vocal tics starting at age 3, and had great difficulty with attention, focus, & hyperactivity. He was diagnosed with ADHD at age 5. At age 6, he began Concerta, which exacerbated his tics alarmingly. Despite the tics, we could not ignore the fact that he was MUCH better able to attend & focus. We added Tenex (.5 mg in a.m. + .5 mg in p.m.), and tics subsided almost completely. By age 9, Concerta dosage increased to 45 mg, at which point we became worried about continually increasing his dosage of stimulant meds, especially given: mild OCD tendencies, his slight weight, and (of greater concern) increasing anxiety levels and sleep problems. Then, last year, I read about Intuniv on this site. After talking to our doc, we marked Spring 2010 (at age 10) as when we’d start a transition. By June 2010, we eliminated Concerta & Tenex, and had transitioned from 1 to 2 to 3 mg Intuniv. He’s been taking 3 mg Intuniv each a.m. (no other meds) for 3+ months (since June). Tics are gone, his anxiety has decreased significantly; he has no more sleep issues; he has gained 10 lbs (he was underweight, going from 65 to 75 lbs since April); and his focus and attention is acceptable. However, he has in the last month or two become increasingly oppositional & irritable. Today, when he presented in a light & happy mood, my husband and I noted in concern that this side of him has become a rarity in the last couple months. We have not made changes in his diet. He is not a picky eater — milk, proteins, fruit, smoothies are a favorite, veggies with dinner, salty & sweet snacks in moderation.
We briefly considered putting him on a gluten-free diet, in part because I was diagnosed with Celiac Disease 3 years ago. My diagnosis was delayed by a decade because I have no IgA (zero), and my docs did not put it together as to why my Celiac blood screens always came back negative. By the time I was at severe stage of CD, we figured out the problem with the blood screen, and an endoscopy made my CD diagnosis clear. Our three sons have all have had genetic testing for CD. They all carry CD genes, but all have negative CD blood screens. The ADHD son at issue has normal IgA levels and shows no GI symptoms of Celiac Disease. So, we have made no dietary changes.
We are resistant to a return to stimulants due to his issues with anxiety, sleep & tics. And, we’re cautiously optimistic about Intuniv and many of its beneficial effects on attention, focus and hyperactivity. He succeeds academically — and continues to do so, despite the transition this Fall to Middle School. Yet, we are nonetheless quite concerned about his seemingly marked increase in irritability & oppositional behavior. His light & happy disposition has dissipated. We have worked with him for years with respect to social awkwardness and difficulty in reading social cues, but he has always been eager, outgoing and friendly. Now, he seems somewhat apathetic about socializing. Could Neuroscience testing reveal deficits that could be improved with supplements, or something else? We are feeling befuddled.
Kim,
Highly likely he has gluten sensitivity even if not celiac. Gluten sensitivity has the same effect on villi and malabsorption with leaky gut as if he had full blown stage 4 gluten sensitivity = celiac. CD genes strongly suggest the diet regardless of GI findings and the *Gold Standard* assessment for celiac – which is really end stage gut immune/sensitivity disease.
cp
Hello Dr Parker,
My son is one of the few that deteriorated while taking Intuniv (and while taking Tenex before intuniv was available). We learned through NT testing that he also has elevated glutamate levels (and dopamine and epinephrine, norepi, serotonin, GABA etc.) I am wondering if you know if Clonidine will also have the same effects on him and his glutamate levels? I know they are medication “brothers” as his MD describes it. We are taking our supplements and waiting for IgG testing but he needs something to help while in school as he is WAY TOO SILLY AND HYPER! Unfortunately Vyvanse and Daytrana and stimulants in general don’t sit well with him and aggravate his Tourette’s. But I wonder if Clonidine is worth trying?
Thanks for your time!
m.roy,
Very likely Clonidine will create the same problem as the Guanfacine products, based likely upon the secondary facilitation of the glutamate. Remember, it isn’t directly an agonist fpr glutamate, but rather facilitates neurotransmission in a secondary way thru closing those ion channels post synaptically.
Mark my word, the IgG testing will likely turn the tide. If it doesn’t you have another level of inquiry, but for right now I would, since you have the testing in, try an elimination diet on the most likely foods: casein if constipated, wheat if more diarrhea. These aren’t always the presentations, but common enough to start there.
cp
Dr. P, It amazes me how much your posts target, coincidentally I have to say, my personal situation. ADHD Appearance, Prefrontal Cortext, Immune Disorders, NeuroPsych,..just to name a few. The evidence is overwhelming (to put it mildly) that science will prove that ADHD is most certainly real! But you know that allready.
Scott.
Scott,
Thanks for your kind remarks! Looks like you are right on the science and details over at your site – excellent reporting! Do sign up for CorePsych Blog for updates and if you wish to review my recent book send me a request offline,
Thanks,
cp
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Functional Brain Science, Immune disorders, biochemistry, physiological connections…More physicians need to be educated on all of the above. Especially on the effects medications have on the brain of children, adolescents, and others. Whereas, the neurotransmitters in the brain are already “misfiring”, and can become very sporadic with “hormonal imbalances” coupled with a possible toxicity within the body. I had gotten saliva testing (endocrine) to reveal that 17 out of 19 neurotransmitters of my teenager were elevated. This was after “detoxing” his body/blood/brain barrier from adhd and sedative meds, in which his cognitive, social, emotional functioning went haywire due to extreme stress. On top of this are the contraindications due to an underlying or causal sleep disorder with parasomnias, and other manifestations present. When I tried to advocate and question the extreme changes in behavior that escalated over a 5 month time frame, pointing out concern for metabolic, systemic and autoimmune dysfunction; I was met with resistance for wanting to eliminate medication. With DNA predisposition of the latter, I find that the recombinant DNA technology, combined with biosciences provide a clearer indication of exactly what is working and what is not in cellular construction. We are now taking the naturalistic, homeopathic, combined integrative approach, finding out and eliminating “allergies”, while seeking accurate medical advice for treatment. It seems that the easy answer from some professionals are to put him on medication…instead of getting the answer relative to how 8+ years of medicine within a growing childs body can negatively interfere with development of overactive or underactive complement system functioning.
Lily,
Sounds like you are becoming an informed consumer! Thanks for weighing in – the details are so compelling!
cp
Okay……now in english please! I have just found this website and it is all new to me, but now all the complications with medication and ADHD. My son is 13 years old and I am at such a loss! I get more and more frustrated everytime I go to the psychiatrist and I know more than he does! My son has been in and out of facilities this year, none of which showed any improvement in his behavior and those facilities are a whole other show! They are not for parents who actually care and are willing to make changes for their family! Anyway, we have not had any positive expreiences with meds. Right now he is on Depokote, just started him back on Intuniv yesterday 4mg, and he will be starting back on the daytrana patch 10mg next week! But, he has done nothing but sleep since he has been back on Intuniv, even in classes. And, the Depokote is making him eat everything in the house, no exageration. The other night he woke up and ate 6 homeade cinnamon rolls in the middle of the night. My husband just had a freezer with a lock on it delivered today. It is all tooo much for me! I just don’t know what to do? What is the “right” answer! I have had evaluation after evaluation and still getting nowhere. I live in Arkansas and I am sure that doesn’t help! He is currently labled emotionally disturbed under the special education act so I can keep him in school. He is at regular intelligence, think 104, but can’t function because of his anger and behavior! Where do I go from here?
Heidi,
You write well, you are smart, you can get this: Spend some time on this Neuroscience Page and really sink into the science – there are, regrettably, no exceedingly easy solutions to these complex issues.
cp
Dear Dr. Parker, I am at a standstill with getting my child adequately tested, diagnosed and treated. The most disturbing symptom which overtly became evident with “extreme stress” complicated by a confirmed underlying sleep disorder and abnormalities in blood works, is chewing on non specific items, mostly plastic and other things that seem to abate the reaction to stress kind of like a PID or compulsiveness to qualm the anxiety. After showing the collection of these things to numerous physicians, therapists, and school admins, with cause for concern—we still have no answers. These items are not being swallowed whole, but are being chewed to the extent that I have questioned the amount of possible digestion. Could there be patho-physiological, systemic, or metabolic syndromes, infection? Neurological, or irregulation of pathways in the body, like autoimmune malfunction? Recent testing showed low NK cells and other abnormalities. The chewing behavior is not daily, in fact it had dissipated for a few months, but now is reappearing since difficulty in school. (LD) I do not know where to take my child for further testings. Could this be unfounded PICA,or PANDAS? Please help me find the right specialist, for I am unable to figure out and am in the process of finding new health professionals willing to answer my questions, and take precise testing like perhaps an fMRI or even digestive tract images. Please help me to help my child…
lilyangel1,
Way too many variables – but each one can be addressed with a comprehensive approach. Why don’t you give Sarah a call, set up a time to chat, and fill out our comprehensive questionnaire, and we can make some long distance suggestions about what-to-do-next? – see services above.
cp