View Full Version : Must read for those who take Clonidine and stims


jasonshadow
09-01-11, 04:14 PM
Dr. Romeo Mariano is probably one the smartest docs you can find. He is one of the leaders in Neruo-Endochronoligy and Psychiatry so I respect his opinions immensly. Here is a response from Dr. Mariano regarding Clonidine that I copied from his his forum. The last paragraph is the most important for folks on this board.

"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. "

Lunacie
09-01-11, 04:50 PM
That's too long for me to read right now, but I just wanted to let you
know that you can get in trouble for copy/pasting that much. The right
way to do it is to copy a paragraph or two and add a link to the article
so others can look it up and read it if they're interested.

jasonshadow
09-01-11, 05:13 PM
That's too long for me to read right now, but I just wanted to let you
know that you can get in trouble for copy/pasting that much. The right
way to do it is to copy a paragraph or two and add a link to the article
so others can look it up and read it if they're interested.


Oops...would like to edit for the life of me cannot find the edit option.

Lunacie
09-01-11, 05:29 PM
Oops...would like to edit for the life of me cannot find the edit option.

The edit option is limited to only about 15 minutes on this forum.
Talk to a moderator about making changes on a post that's older.

sarahsweets
09-01-11, 06:31 PM
Either way someone is going to have to dumb this down for me.

jasonshadow
09-01-11, 07:27 PM
Either way someone is going to have to dumb this down for me.

Basically by taking Stims with Clondidine at the same time, the Clonidine which usually blocks the Adrenalin which helps for someone who is hyper can actually have the opposite effect and cause tachycadia (fast heart beat) and basically make them more hyper. So in short, taking Clonidine in the evening is a better aproach.

BR549
09-01-11, 08:30 PM
Clonidine is an off-label treatment for ADHD. It's used to treat hypertension. It works by stimulating the receptors on nerves in the brain. That reduces the transmission of messages from those receptors to other nerves in the body resulting in decreased heart rate, reduction of blood pressure, opening of blood vessels. It has sedating qualities.

The only stimulant drug-Clonidine interaction report that I could find was for Clonidine ER and all forms of methylphenidate. The FDA also has a report of this interaction. What I found states that methylphenidate may decrease the effectiveness of drugs used to treat hypertension. I couldn't find any other information about interactions with other ADHD medications.

Scroll down to drug interactions:
www.drugs.com/pro/metadate-er.html
www.drugs.com/drug-interactions/clonidine-er-with-ritalin-sr-704-14317-1606-4667.html

As with any medication, it's good to be aware of any potential drug interaction or possible side effect.

Jasonshadow, I looked all over for the information you posted. I could find info on Dr. Mariano, but nothing on his opinion on Clonidine and stimulant interactions. I'd like to read more. Can you direct me to where you got this info? Was it a web-site or a book?

namazu
09-01-11, 09:12 PM
Basically by taking Stims with Clondidine at the same time, the Clonidine which usually blocks the Adrenalin which helps for someone who is hyper can actually have the opposite effect and cause tachycadia (fast heart beat) and basically make them more hyper. So in short, taking Clonidine in the evening is a better aproach.
Hmmm...this is not something I'd heard before.

It's also not something I've experienced, either. I take clonidine both at night and in the AM, and when I take it in the morning, I take it with methylphenidate. Thus far, I have found clonidine to be extremely helpful in reducing restless feelings/hyperactivity and also some compulsive/tic-like behaviors. (It also helps my significant other sleep *much* better -- when I take it!)


Clonidine is an off-label treatment for ADHD.
This is no longer entirely true. There is now a formulation of clonidine that is FDA-approved for treatment of ADHD, marketed as "Kapvay". However, you're right that it was used for many years off-label before that, and some of the other versions of clonidine are still used to treat ADHD as well.

BR549
09-01-11, 09:58 PM
I completely forgot about Kapvay! Thanks for the reminder.

jasonshadow
09-01-11, 11:42 PM
Clonidine is an off-label treatment for ADHD. It's used to treat hypertension. It works by stimulating the receptors on nerves in the brain. That reduces the transmission of messages from those receptors to other nerves in the body resulting in decreased heart rate, reduction of blood pressure, opening of blood vessels. It has sedating qualities.

The only stimulant drug-Clonidine interaction report that I could find was for Clonidine ER and all forms of methylphenidate. The FDA also has a report of this interaction. What I found states that methylphenidate may decrease the effectiveness of drugs used to treat hypertension. I couldn't find any other information about interactions with other ADHD medications.

Scroll down to drug interactions:
www.drugs.com/pro/metadate-er.html (http://www.drugs.com/pro/metadate-er.html)
www.drugs.com/drug-interactions/clonidine-er-with-ritalin-sr-704-14317-1606-4667.html (http://www.drugs.com/drug-interactions/clonidine-er-with-ritalin-sr-704-14317-1606-4667.html)

As with any medication, it's good to be aware of any potential drug interaction or possible side effect.

Jasonshadow, I looked all over for the information you posted. I could find info on Dr. Mariano, but nothing on his opinion on Clonidine and stimulant interactions. I'd like to read more. Can you direct me to where you got this info? Was it a web-site or a book?

Here is his forum http://www.definitivemind.com/. Just do a search for Clonidine. Unfortunatly he so busy he rarely answers questions anymore. There still some good info to glean from.

dannn
09-05-11, 09:13 AM
This is my psych approach as well, he is against mixing stims and clonidine, but he wants to increase clonidine dose until it becomes stimulating.