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Clonidine lower noradrenaline decrease anxiety

Discussion in 'General Treatment' started by heapsreal, Nov 8, 2011.

  1. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Dr. Mariano,

    Have you ever used Clonidine to help reduce norepinephrine to reduce anxiety. Does this have the same effect on dopamine - i.e. do side effects include lower libido, ED, etc.

    While I consider psychotherapy to help with anxiety, I wonder if there are ANY medical interventions that dont have sexual side effects.

    thanks again.

    Remember that I am a psychiatrist. A psychiatrist can use a far greater range of medications than most physicians.

    I am very familiar with Clonidine and certainly use it as part of my toolkit.


    CLONIDINE:

    Clonidine and its sister, Guanfacine, are Adrenergic alpha-2 receptor selective agonists. They are also I1 Imidazoline Receptor agonists. Note that anytime the world "selective" is used, this means that it also works on other receptors but prefers one versus the other. "Selective" is a weasel word in pharmacology.

    The I1 Imidazoline receptors in many functions including control of blood pressure, pain management, etc., though they usually don't include anxiety, alertness, wakefulness functions like the adrenergic receptors do. Agonists of I1 Imidazoline receptors reduce blood pressure and helps reduce pain.

    Adrenergic receptors have subtypes, which include the Alpha-1, Alpha-2, Beta-1, and Beta-2 receptors. Adrenergic receptors respond to both norepinephrine (noradreline) and epinephrine (adreneline). Alpha-2 receptors occur primarily in the brain. Alpha-2 receptors are both pre-synaptic and post-synaptic.

    The pre-synaptic alpha-2 receptor is of interest since stimulating it reduces norepinephrine output from norepinephrine-releasing neurons of the norepinephrine system in the nervous system (which originates from the locus ceruleus and the lateral tegmental field). It functions like a thermostat, providing negative-feedback inhibition of norepinephrine output.

    Clonidine, by stimulating alpha-2 receptors, reduces norepinephrine output from the norepinephrine system. Guanfacine (Tenex) is weaker in this regard and is thus not as sedating.

    Clonidine only works 80% of the time on alpha-2 receptors. 20% of the time, it works like norepinephrine as an agonist on the other receptors. In the body, it actually acts as a stimulant 100 % of the time, just like norepinephrine, rather than acting as an anti-norepinephrine. But its ability to reduce norepinephrine signaling in the nervous system generally outweighs the stimulant part - for most people. It's stimulant effects can lead to side effects such as dry mouth, constipation. The norepinephrine-reducing action in the central nervous system causes sedation, dizziness, reduction in cardiac outflow (a consideration in treating patients with congestive heart failure).

    Clonidine has many uses. In general medicine, it is primarily used to reduce blood pressure. It is also used as a pre-anesthetic agent. In psychiatry, it can be used for the treatment of migraine, nicotine addiction, opiate withdrawal, menopausal flushing, attention deficit/hyperactivity disorder, posttraumatic stress disorder, Tourette Syndrome, panic and anxiety disorders. In clinical use, I haven't found it as useful for anxiety since it can cause excessive daytime sedation.

    Regarding sexual function, if the dose is too high, it also will reduce libido and the ability to have an orgasm. Norepinephrine also participates in sexual function - such as providing the excitement of sex and in trigger the orgasm. Inhibiting norepinephrine too much would not only reduce sex drive, but make one too sleepy to have sex in the first place.

    Clonidine does not work with everyone. For example, some people become more anxious or do not sleep at all despite treatment with Clonidine. I hypothesize some people have a variant Alpha-2 receptor where Clonidine and norepinephrine do not fit fully well. This results in a nervous system which tends to be shifted to a high stressed state. The thermostate, so to speak, is broken. Generally, the anti-stress signaling systems can balance this and the person can function well. But after a time, through stresses, aging, etc. these systems lose function, then the person becomes ill.

    If the dose of Clonidine is too high, the alpha-2 receptors can become saturated with Clonidine. Any further increase in Clonidine only increases its norepinephrine-like stimulant effects. Thus, past a certain dose, Clonidine works primarily as a stimulant rather than as a norepinephrine-reducing agent. It would cause insomnia, rather than sedation.

    Care must be taken when used with stimulants, such as amphetamines. When a stimulant and Clonidine are working simultaneously, the stimulant can overpower Clonidine's alpha-2 agonist effects (it's norepinephrine-reducing effects). This means Clonidine will work primarily as a stimulant which has additive effects with the stimulant medication. This can cause significant problems such as tachycardia or other arrhythmias. A lot of physicians don't realize this, thinking Clonidine only has Alpha-2 agonist effects, not stimulant effects, since the alpha-2 agonist effects are the only ones listed in textbooks. When used in combination, my preference is to limit Clonidine to the evening so that its effects can wear out by the time a stimulant is started in the morning. Then, the simultaneous stimulant effects can be avoided as much as possible. I would avoid giving Clonidine in the daytime along with a stimulant. Since many psychiatrists if not most of them do not take vitals as I do, they may not realize they are causing tachyarrhythmias in the kids they treat with Clonidine and stimulants in the daytime. As I said above, the world "selective" is a weasel-word in pharmacology. A receptor-selective medication is not totally receptor-selective, it works on other receptors as well.

    -----------------

    REGARDING ANXIETY TREATMENTS:

    With any medication for anxiety, realize that dosing is important. The higher the dose of ANY treatment for anxiety, the more likely impairment of sexual function or other side effect occurs. Thus, I would reduce the dose to find the minimum dose that doesn't have the unwanted side effect, then add another medication that uses a different mechanism. I call this a complex treatment.

    Serotonin Reuptake Inhibitors are very useful for reducing anxiety. If the dose is too high and causes sexual dysfunction, I would simply reduce the dose until this effect is gone, keeping whatever dose is left for reducing anxiety. Then if anxiety is still prominent, I would add another medication with another mechanism of action to attack the problem of excessive anxiety, such as by adding a benzodiazepine or other medication. If an SSRI cannot be used at all, I would choose alternative mechanisms to treat the causes of anxiety.

    In regard to anxiety, anxiety can be a side effect itself of increased norepinephrine levels which are a compensation for another problem. For example, when thyroid hormone is low, norepinephrine is increased by the brain in an attempt to improve energy production. Norepinephrine increases the production of 5'-deiodinase enzyme, which then improves conversion of T4 to T3, improving the effectiveness of whatever thyroid hormone is left. In this case, adding thyroid hormone to treatment helps avoid this compensation, thus reducing anxiety. Thus, when examining why a patient is having anxiety, the causes of a compensatory increase in norepinephrine production are important to find. This avoids having to add a medication to the mix since it would help restore normal norepinephrine signaling tone.

    http://www.definitivemind.com/forums/archive/index.php/t-83.html
  2. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Reducing noradrenaline is something im looking into as an aid to helping improve sleep. I dont feel like i have anxiety as such but feel more like i have normal noradrenaline levels but they just dont switch off at night when they are suppose. I look at gaba drugs(traditional sleeping pills) as breaks and noradrenaline as the accelerator, when we take sleeping pills its like driving with the break on, although we sleep, quality is poor. I think if we can reduce this noradrenaline at night we could start sleeping well again or maybe get better results from sleep meds when combines with an alpha2 adrenergic med.

    Another med thats used alot for sleep that acts on alpha2 noradrenaline receptors is the muscle relaxer zanaflex/tizanadine. I have used this own its own and it helped abit and i think i have used it with gaba meds and slept well but cant quite remember. So i have ordered some zanaflex and will retest it again. There are probably many other similar meds, many being blood pressure meds.

    cheers!!!
  3. alex3619

    alex3619 Senior Member

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    Hi, heaps and I have been talking about clonidine for a while. I had more than a decade with circadian sleep dysruption, finally winding up with non-24 hour circadian issues, quite severe. I am on 50 MICROgrams of clonidine before bed. I now wake up regularly between 6 and 9 am depending on how wiped out I am. That dose is about half that for a child.

    For the record, I have high bp, circadian and other sleep issues, and neuropathy. Clonidine is used to treat all three. I also have orthastatic intolerance, and clonidine has been used to treat adrenergic POTS. It was also noted at the Ottawa conference by a Japanese researcher that clonidine helps circadian sleep issues.

    Bye
    Alex
    taniaaust1 likes this.
  4. Sushi

    Sushi Moderator and Senior Member Albuquerque

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    Funny about clonidine! It was one of the worst drugs I tried and put me into my lowest level of functioning--even on a tiny dose. I did much better with OI on drugs that increased norepinephrine.

    Again, we are all different! I also know people who did well on clonidine.

    Best,
    Sushi
  5. alex3619

    alex3619 Senior Member

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    Hi sushi, rule 22:

    Most treatments for ME are lemons, they don't suit everyone - but you often wont know if it suits you until you suck it and see. If you see a soured look on my face you will know why.

    Bye, Alex
  6. Emootje

    Emootje Senior Member

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    This video inspired me and gave me new idea's how to lower my norepinephrine (anticonvulsants, heroin:D and LDN)

    [video=youtube;eitnp1iVkeA]http://www.youtube.com/watch?v=eitnp1iVkeA[/video]]

    So far, only deep breathing helped. I'm now also researching copper toxicity as a cause of increased norepinephrine. Copper is an important co-factor in the dopamine ?-hydroxylase enzyme which converts dopamine to norepinephrine. If you decrease copper I think you get more dopamine and less norepinephrine, but I'm not sure because copper is also needed to degrade norepinephrine (monoamine oxidase needs a little bit of copper).
  7. merylg

    merylg Senior Member

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  8. Emootje

    Emootje Senior Member

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    Rockin' chair therapy for ME/CFS, I like it!
  9. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Emootje, interesting lecture, thanks. Does this guy do anymore interesting lectures that we would find just as interesting.
    Rocking chair sounds good, maybe a hammock too.
  10. taniaaust1

    taniaaust1 Senior Member

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    Thank you alex.. your post has made me aware I probably should add that one on the list ..it may be that which ends up helping my severe insomina (Im only getting 4 to 5.5 hrs sleep most nights so are so tired due to that rather then other kind of exhaustion). I also have the adrenergic POTS and high norepinephrine level on blood tests.

    This morning I hallucinated due to the lack of sleep and the flowers on my quilt.. looked like big spiders crawling all over it which scared the crap out of me till I realised I was seeing things.

    very interesting.. as on my hair analsyses test I had extemely high copper.
    .......................

    Heaps.. I still havent contacted your doctor.. just too tired to really talk to anyone today due to not enough sleep.
    Im going to make my main activity tomorrow to ring his clinic and try to talk to him to see if he'll take me on, ring my other CFS specialist (for something Im sure he will say no too as he's told me before he wont do prescriptions) and now also need to ring that melbourne hospital as the email address for the POTS doctor on their site.. it was wrong. (just my luck.. i only just today noticed my email bounced back).

    The doctor in the next town to me which the other who has ME/CFS was checking out and thought may turn out okay so I also was considering depending on how it turned out for her.. its turned out she isnt okay. That doctor has refused to allow the other to go back onto B12 injections which used to help her as she dont like people trialing anything. So it looks like I only do have your doc to try to turn to for help. If he'll take me on, I"ll now probably ask him about Clonidine too :p (thou I will try to a higher melotonin dose first).

    (Ive put this here and not pmed you as I know you will see it and there also was a few others wondering how my doctor hunt is going..so hopefully they will see my post on it all here too).
  11. Emootje

    Emootje Senior Member

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    TBN32 has more interesting lectures (916 video's) unfortunately 99,9% of them are private.
    http://www.youtube.com/user/tbn32
    You can partly bypass this by subscribing to his youtube channel and by clicking on the related suggestions in youtube while playing his video's.
  12. Gypsy

    Gypsy Senior Member

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    Am I some sort of freak???.... Or what because I had a similar reaction to clonidine as I did to amitryptyline. Yes, I know they are in a completely different class of medications, but I took Clonidine 0.1mg and NO SLEEP just like when I took Amitryptyline. It did something to my brain. Could Clonidine actually have increased norephinephrine in my case?
  13. Lotus97

    Lotus97 Senior Member

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    When Clonidine wears off it can sometimes cause rebound (increased) hypertension/blood pressure and a spike in norepinephrine/noradrenaline.
  14. invisiblejungle

    invisiblejungle Senior Member

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    I had the same reaction to guanfacine (clonidine's sister). It definitely felt like it increased my norepinephrine instead of decreasing it. My doctor at the time told me that it has paradoxical reactions for some people.

    My guess is that for some of us, the body's drive to produce norepinephrine is so great that it goes into hyper-drive in order to overcome the clonidine/guanfacine's effect.
  15. Lotus97

    Lotus97 Senior Member

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    I've been taking Clonidine for the past few days at it seems to make my nose stuffy. Since I stopped Flonase 4-5 months ago my congestion has mostly been under control. Maybe this has something to do with a drying effect.
  16. adreno

    adreno 3% neanderthal

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    NE contracts blood vessels and mucus membranes. Blocking NE release has the opposite effect.
    Lotus97 likes this.
  17. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    another alpha adrenergic antagonist is tizanadine, which is used as a muscle relaxant and for sleep, has a shorter half life then clonidine that might be useful for some, especially if they just need it for sleep.
  18. Lotus97

    Lotus97 Senior Member

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    Are there any dependence/tolerance issues?
  19. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    i dont know, i guess there is like most things. I just use it occassionally. Found it worked well when i couldnt sleep after using adrafinil which does work on alpha adrenergic receptors, so i think tizanadine blocked the effect on those receptors and helped me get to sleep those nights.
  20. Lotus97

    Lotus97 Senior Member

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    Well, maybe I can cycle some of my sleep meds. I have ambien that I just take when I wake up early and can't fall asleep, but that seems like almost every night. Something I've been thinking out recently. Sleep (or lack thereof) has made a big difference in my overall health, but it could also be the reverse. I think after my health has worsened it has also been contributing to my insomnia. Sort of a vicious cycle.

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