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Thread: Guanfacine and glutamate

  1. #1
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    Default Guanfacine and glutamate

    Hello all,
    This evening we started my son on 1mg of guanfacine (Intuniv). I had been doing my research about it and decided to read up some more tonight and I came across this statement:
    "It appears that Intuniv (guanfacine) works in the pre-frontal cortex to help the brain to increase the available supply of glutamate, an excitatory neurotransmitter."
    from this website:
    Intuniv for ADHD

    I don't know how reliable this information is, but what it says confuses me. I thought that having too much glutamate was a bad thing, and we would want less excitatory neurotransmitters, so why would increasing the supply of glutamate help decrease tics?

    If this is not correct, then how does guanfacine actually work?

    Thanks!

  2. #2
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    Default Re: Guanfacine and glutamate

    MomofX,

    I cannot answer your question specifically at this time, but will research your query further and get back to you.

    Guanfacine is in the category of medications known as alpha agonists, which are non anti psychotics that are prescribed to manage tics, and have beneficial effects on ADHD as well. Alpha agonists are generally better tolerated than anti psychotic class of medications for these indications.

    Though it may not be relevant to this question, it might be noted that stimulant medications (Ritalin) are prescribed to manage ADHD symptoms and have what medical professionals call a paradoxical effect.

    However, this article may give a bit of insight into your question in the meantime:

    Neuropsychopharmacology - Stimulants: Therapeutic Actions in ADHD

  3. #3
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    Default Re: Guanfacine and glutamate

    Guanfacine Mechanism of Action
    Medscape Psychiatry & Mental Health
    Pediatr Pharm. 2008;14(4)

    Guanfacine, like clonidine, is a centrally acting selective alpha-2 adrenergic agonist. Stimulation of alpha-2 adrenergic receptors in the prefrontal cortex results in enhanced executive functioning, increased attentiveness, and improvements in working memory. In patients with ADHD, improved neurotransmission in this region increases the ability to control or inhibit inappropriate behaviors and increase focus. Guanfacine preferentially binds alpha-2A receptors, compared to the more general affinity of clonidine for alpha-2A, B, and C and imidazoline receptors.
    Quote Originally Posted by MomofX
    how does guanfacine actually work?
    Attached are two complete Medscape technical articles outlining the pharmacology and pharmacodynamics of guanfacine, that is, describing how this medication works. The action on glutamate is not clear to me at this point, and requires further research.
    Attached Files Attached Files

  4. #4
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    Default Re: Guanfacine and glutamate

    But my son doesn't have ADHD. And when he tried clonidine, it didn't do anything for him. I'm wondering why guanfacine would work. Dr. says it will take 2-3 weeks to see any effect. Right now, all I can say is that today and yesterday, when he first started taking it, his vocal tics have increased - lots more shrieking and swearing again.

    Thanks for the links Steve.

  5. #5
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    Default Re: Guanfacine and glutamate

    Have you communicated your concerns and reported the emergence of vocal symptoms to the prescribing doctor?

    As we know, stress and fatigue are factors that can make tics worse. Is it possible you son feels under scrutiny since he began taking the medication, which might be stressing him and might account for the emergence of the tics?

    Intuniv (guanfacine) is one of the options prescribed to manage tic symptoms, as an alternative to clonidine, witht he extended release (ER) form often prescribed for ease of administration. If a child has ADD as well, Intuniv appears to help control the ADD symptoms as well.

    We are told that 30 - 40% of children (people) diagnosed with Tourette have associated ADD or ADHD, which is probably why this medication has such wide appeal among treating physicians.

  6. #6
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    Default Re: Guanfacine and glutamate

    Steve, what do you think of this article (if you have time to check it out): Special Needs Digest: ADHD Neurology: The Brain of Inattention, Impulsivity and Hyperactivity
    It says:
    Their work, along with the work of many others, is often focused on the a2-receptor sites in the pre-frontal cortex. They have reported on the benefits of norepinephrine at these sites, and have also shown the benefits of stimulating these receptor sites with the medication guanfacine (intuniv) which increases glutamate production in the PFC. It appears that by doing this, guanfacine improves cognitive functioning in the pre-fronatl cortex. This is potentially exciting because Intuniv (guanfacine) is not a stimulant medication.As


    I don't know how reliable this source is.
    As I mentioned in my first post, I always thought excess glutamate was what we are trying to avoid b/c it causes more tics. It seems reducing glutamate is supposed to reduce tics - from what I have read online.

    I'm just trying to figure out what is going on! It bothers me that no one really knows :P

  7. #7
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    Default Re: Guanfacine and glutamate

    I'm working on trying to get you some information, MomofX. It may take a little while, because I want to be sure of the accuracy of the information I provide for your query.

  8. #8
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    Default Re: Guanfacine and glutamate

    Thanks for all your help Steve.

    This Victoria Day long weekend was pretty good. My son even wanted to go swimming with his sister and me, I was surprised, since one of his tic triggers is feet. LOL His tics are usually up during weekends with no routine and 'nothing' to do, but this weekend was a pleasant surprise. He had been on the Intuniv since Monday.

    Unfortunately, today was less good and this evening his screaming vocal tic came back. I wasn't home but when I came back this evening, he was in bed and very sad. I am trying to explain to him that there is no 'magic pill' and this will be a gradual, long term process but what 10 year old wants to hear that??

    Steve, do you know of any resources that would allow us to do some sort of CBT with him at home while we wait for a spot with the psychologist?

  9. #9
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    Default Re: Guanfacine and glutamate

    Thanks to the knowledge and expertise of a a reliable source I know, I believe I have some information that may help understanding your original question:

    Quote Originally Posted by MomofX
    How does guanfacine actually work?
    In reading the post, (there may be some misunderstanding in terminology) "excitatory" with "exciting" behavior".

    The neurotransmitter glutamate does excite certain neurons, but this doesn't always translate to an excited behavior. In the Pre-Frontal Cortex (PFC), where it is thought to have its beneficial effect, guanfacine excites glutamate dependent neurons, thereby strengthening their network connections, which in this case, leads to a variety of positive effects in the treatment of ADHD, such as: working memory improvement, distractibility reduction, response inhibition improvement, and enhanced attention and impulse control (Wikipedia).

    The technical neuro-physiological answer can be summed up thus:
    "PFC neuronal networks interconnect via glutamate synapses on dendritic spines. Guanfacine appears to strengthen PFC network connections by stimulating postsynaptic a2A receptors on the dendritic spines of PFC pyramidal cells, the sites of PFC network connections. Stimulation of these a2A receptors with NE or guanfacine inhibits local cAMP production, which in turn closes nearby ion channels that make the membrane “leaky”. Closing of these channels strengthens glutamatergic synaptic inputs onto the spine, increasing network firing and allowing greater control over attention and behavior. This strengthening of PFC neuronal firing is reflected in greater cerebral blood flow to the PFC." (Neuropsychiatr Dis Treat. 2008 Jun; 4(3): 499–506.)

    The status of guanfacine's efficacy in ADHD treatment is much clearer that in the treatment of tic disorders. There is evidence that guanfacine is useful when elements of both tic disorder and ADHD are present, but I think there is more work needed on that.Source: Dr. R.W.
    Additionally the attached TSA article on medications may offer some further insight.



    Steve, do you know of any resources that would allow us to do some sort of CBT with him at home while we wait for a spot with the psychologist?
    I am glad to hear that your son is on a waiting list to be seen by a psychologist.

    The number of mental health professionals in Canada trained in behavioural therapy specifically designed for children with Tourette is very limited. My own opinion, which reflects the view of Tourette Canada is that behavioural therapy to manage Tourette and related symptoms should be administered by a medical professional, even if it is not a CBIT trained individual.

    Alternatives might be so seek out a mental health professional to use traditional CBT models to help manage some of the associated issues, and perhaps even employ some traditional Habit Reversal Therapy techniques.

    There are a number of articles and videos in our CBIT Forum section explaining the comprehensive approach to managing TS symptoms.

    To learn more about the actual techniques employed by CBIT therapists, this book is the one used in the training course.

    Other resources that might offer some insights might be Duncan McKinlay's book Nix Your Tics

    What specific symptoms does you son hope to manage through behavioural therapies?
    Attached Files Attached Files

  10. #10
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    Default Re: Guanfacine and glutamate

    It was suggested to me by my own psychologist (I am seeing to help me deal with the stress of all this that has happening in the past 1.5 years) that my husband and I speak with someone who can give us tips on how to handle my son's tics. Lately, my son is trying to expose himself to his triggers (on his own, without any prompting from us) and of course, it makes him tic violently but he says he is trying to do this to 'help his tics'. The problem is, he doesn't know what to do once he's triggered himself - i.e. how to control the tic, or lessen it.

    Thanks again for all your help, Steve. I'm going to call our neurologist tomorrow morning, as my son's tics (motor but especially vocal - lots of screaming tonight) continue to increase. I don't know if the Intuniv could have this kind of effect, but these medications could have the opposite effect of what they intend to do in some people so I'm concerned.

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