Psycho-Babble Medication Thread 1110839

Shown: posts 1 to 16 of 16. This is the beginning of the thread.

 

Why does Mirtazapine cause Restless Legs Syndrome?

Posted by Skeletor on June 19, 2020, at 13:32:58

Why does Mirtazapine cause Restless Legs Syndrome? Mirtazapine is known to often provoke restless legs syndrome (RLS). Mirtazapine has an approximate 30% chance of inducing it; by comparison, paroxetine, sertraline, and other psychiatric medications only have an approximate 5% chance of causing RLS symptoms.

Why is Mirtazapine prone to causing RLS?

 

Re: Why does Mirtazapine cause Restless Legs Syndrome?

Posted by Hugh on June 19, 2020, at 14:20:15

In reply to Why does Mirtazapine cause Restless Legs Syndrome?, posted by Skeletor on June 19, 2020, at 13:32:58

Interesting. I wasn't aware of that. I used to take mirtazapine, but it didn't give me RLS. It did make me very tired, and it gave me a voracious appetite. I gained 20 pounds while on it.

 

Re: Why does Mirtazapine cause Restless Legs Syndrome? » Hugh

Posted by Skeletor on June 19, 2020, at 15:09:44

In reply to Re: Why does Mirtazapine cause Restless Legs Syndrome?, posted by Hugh on June 19, 2020, at 14:20:15

> Interesting. I wasn't aware of that. I used to take mirtazapine, but it didn't give me RLS. It did make me very tired, and it gave me a voracious appetite. I gained 20 pounds while on it.

Yeah, it's very interesting, especially that high percentage. No one seems to know why. They say that it might be due to its strong antihistamine properties. Some experts have proposed that it is due to its 5HT2 antagonist properties. But then other strong antihistamines and 5HT2 antagonists should also be prone to cause RLS, e.g. Amitriptyline, Nortriptyline, Doxepine etc., but they don't seem to cause it as frequently as Mirtazapine. One could argue that it is due to anticholinergic properties, which might have a counterbalancing effect.

Some say that it may be Mirtazapine's pro-noradrenergic properties, but shouldn't we see it with other NRIs and pro-noradrenergic drugs? Many questions, no definitive answers...

 

Re: Why does Mirtazapine cause Restless Legs Syndrome?

Posted by ed_uk2010 on June 20, 2020, at 8:55:42

In reply to Why does Mirtazapine cause Restless Legs Syndrome?, posted by Skeletor on June 19, 2020, at 13:32:58

I can't take more than 15mg mirtaz. Otherwise, it makes me very restless but very drowsy.

It's due to the alpha-2 NE antagonism.

 

Re: Why does Mirtazapine cause Restless Legs Syndrome?

Posted by undopaminergic on June 20, 2020, at 10:02:44

In reply to Re: Why does Mirtazapine cause Restless Legs Syndrome? » Hugh, posted by Skeletor on June 19, 2020, at 15:09:44

> > Interesting. I wasn't aware of that. I used to take mirtazapine, but it didn't give me RLS. It did make me very tired, and it gave me a voracious appetite. I gained 20 pounds while on it.
>
> Yeah, it's very interesting, especially that high percentage. No one seems to know why. They say that it might be due to its strong antihistamine properties. Some experts have proposed that it is due to its 5HT2 antagonist properties. But then other strong antihistamines and 5HT2 antagonists should also be prone to cause RLS, e.g. Amitriptyline, Nortriptyline, Doxepine etc., but they don't seem to cause it as frequently as Mirtazapine. One could argue that it is due to anticholinergic properties, which might have a counterbalancing effect.
>
> Some say that it may be Mirtazapine's pro-noradrenergic properties, but shouldn't we see it with other NRIs and pro-noradrenergic drugs? Many questions, no definitive answers...
>

I agree it's interesting.

Citing: https://www.researchgate.net/publication/229667661_Influence_of_Low-Dose_Doxepin_on_Periodic_Leg_Movements_in_Sleep_in_Primary_Insomnia_Patients
"Treatment with low-dose doxepin appears to exert only a weak influence on PLMS in patients with primary insomnia."

Based on that, I'm inclined to rule out histamine-H1 antagonism.

Mirtazapine has a relative lack of antimuscarinic (anticholinergic) potency... I think this is highly significant. Most other 5-HT2-antagonists, including clozapine and cyproheptadine, are highly antimuscarinic.

Clonidine is sometimes used to treat RLS. So maybe the alpha2-adrenoceptor antagonism, especially postsynaptically, of mirtazapine does play a role.

-undopaminergic

 

Re: Why does Mirtazapine cause Restless Legs Syndrome? » ed_uk2010

Posted by linkadge on June 21, 2020, at 8:01:05

In reply to Re: Why does Mirtazapine cause Restless Legs Syndrome?, posted by ed_uk2010 on June 20, 2020, at 8:55:42

>It's due to the alpha-2 NE antagonism.

I concur with this. Alpha-2 antagonists can augment dopamine blockers in the treatment of schizophrenia. Combining alpha-2 antagonism and d2 antagonism can result in antipsychotic effects with a lower degree of d2 blockade. This suggests that alpha-2 antagonists may have a dopamine lowering effect (at least in certain brain regions).

 

Re: Why does Mirtazapine cause Restless Legs Syndrome? » undopaminergic

Posted by Skeletor on June 21, 2020, at 13:03:36

In reply to Re: Why does Mirtazapine cause Restless Legs Syndrome?, posted by undopaminergic on June 20, 2020, at 10:02:44

> > > Interesting. I wasn't aware of that. I used to take mirtazapine, but it didn't give me RLS. It did make me very tired, and it gave me a voracious appetite. I gained 20 pounds while on it.
> >
> > Yeah, it's very interesting, especially that high percentage. No one seems to know why. They say that it might be due to its strong antihistamine properties. Some experts have proposed that it is due to its 5HT2 antagonist properties. But then other strong antihistamines and 5HT2 antagonists should also be prone to cause RLS, e.g. Amitriptyline, Nortriptyline, Doxepine etc., but they don't seem to cause it as frequently as Mirtazapine. One could argue that it is due to anticholinergic properties, which might have a counterbalancing effect.
> >
> > Some say that it may be Mirtazapine's pro-noradrenergic properties, but shouldn't we see it with other NRIs and pro-noradrenergic drugs? Many questions, no definitive answers...
> >
>
> I agree it's interesting.
>
> Citing: https://www.researchgate.net/publication/229667661_Influence_of_Low-Dose_Doxepin_on_Periodic_Leg_Movements_in_Sleep_in_Primary_Insomnia_Patients
> "Treatment with low-dose doxepin appears to exert only a weak influence on PLMS in patients with primary insomnia."
>
> Based on that, I'm inclined to rule out histamine-H1 antagonism.
>
> Mirtazapine has a relative lack of antimuscarinic (anticholinergic) potency... I think this is highly significant. Most other 5-HT2-antagonists, including clozapine and cyproheptadine, are highly antimuscarinic.
>
> Clonidine is sometimes used to treat RLS. So maybe the alpha2-adrenoceptor antagonism, especially postsynaptically, of mirtazapine does play a role.
>
> -undopaminergic
>

I wouldn't rule out histamine-H1 antagonism per se... for example I get RLS on a lowish dose of Promethazine (15mg) and that is primarily an antihistamine and has moderate anticholinergic properties. Its dopamine-antagonist properties are clinically insignificant...

alpha2-adrenoceptor antagonism as a potential cause... interesting. Might play a role.

 

Re: Why does Mirtazapine cause Restless Legs Syndrome?

Posted by Skeletor on June 23, 2020, at 15:07:00

In reply to Why does Mirtazapine cause Restless Legs Syndrome?, posted by Skeletor on June 19, 2020, at 13:32:58

http://www.eurlssg.org/downloads/abstract_allen_12-08.pdf

https://www.reddit.com/r/insomnia/comments/3en51v/could_it_be_that_it_finally_has_a_name_restless/

 

Re: Why does Mirtazapine cause Restless Legs Syndrome? » Skeletor

Posted by linkadge on June 24, 2020, at 7:56:22

In reply to Re: Why does Mirtazapine cause Restless Legs Syndrome?, posted by Skeletor on June 23, 2020, at 15:07:00

Hi Skeletor,

While you could be right, I would point out a few issues with the first link (study). Diphenhydramine is also a fairly potent serotonin reuptake inhibitor (believe it or not). SSRIs have also been linked to RLS, perhaps by reducing dopamine release. Also, if histamine receptors are elevated in RLS, this could indicate a hypersensitivity to histamine, for which an antihistamine action might help.

This study (in rats) suggests that while there is an elevation of histamine receptors in RLS (primarily h3 receptors), thioperamide (an antihistamine) improved RLS symptoms. They used an iron depletion model to induce RLS like symptoms in mice. Their conclusion was "Histamine H3R antagonists may be useful for the treatment of RLS."

https://academic.oup.com/sleep/article/43/2/zsz223/5610750

Also, anticholinergics can sometimes induce motor activation. It could be that the anticholinergic effects of diphenhydramine are involved.

Here is a case where hydroxyzine (strong antihistamine without SSRI properties) improved RLS.

https://print.ispub.com/api/0/ispub-article/9969


Linkadge

 

Re: Why does Mirtazapine cause Restless Legs Syndrome? » linkadge

Posted by Skeletor on June 24, 2020, at 8:50:58

In reply to Re: Why does Mirtazapine cause Restless Legs Syndrome? » Skeletor, posted by linkadge on June 24, 2020, at 7:56:22

> Hi Skeletor,
>
> While you could be right, I would point out a few issues with the first link (study). Diphenhydramine is also a fairly potent serotonin reuptake inhibitor (believe it or not). SSRIs have also been linked to RLS, perhaps by reducing dopamine release. Also, if histamine receptors are elevated in RLS, this could indicate a hypersensitivity to histamine, for which an antihistamine action might help.
>
> This study (in rats) suggests that while there is an elevation of histamine receptors in RLS (primarily h3 receptors), thioperamide (an antihistamine) improved RLS symptoms. They used an iron depletion model to induce RLS like symptoms in mice. Their conclusion was "Histamine H3R antagonists may be useful for the treatment of RLS."
>
> https://academic.oup.com/sleep/article/43/2/zsz223/5610750
>
> Also, anticholinergics can sometimes induce motor activation. It could be that the anticholinergic effects of diphenhydramine are involved.
>
> Here is a case where hydroxyzine (strong antihistamine without SSRI properties) improved RLS.
>
> https://print.ispub.com/api/0/ispub-article/9969
>
>
> Linkadge
>

Interesting indeed, and quite confusing. On the other hand I never got RLS on SSRIs. I got it on Promethazine and Mirtazapine. Meanwhile Gillman recommends TCAs in case someone has RLS, but maybe their 5HT2 blocking and anti cholinergic mechanisms help to offset that? There is also evidence endogenous opioids are involved and many report opioids and kratom work well for RLS, BUT opioids induce histamine release, so it could just be a histamine thing? F*ck knows... interesting anyway.

 

Re: Why does Mirtazapine cause Restless Legs Syndrome?

Posted by undopaminergic on June 24, 2020, at 15:34:20

In reply to Re: Why does Mirtazapine cause Restless Legs Syndrome? » linkadge, posted by Skeletor on June 24, 2020, at 8:50:58

>
> BUT opioids induce histamine release, so it could just be a histamine thing?

Some opioids, including morphine, induce the release of histamine from mast cells, which may lead to itching, but (AFAIK) they don't release histamine in the CNS.

-undopaminergic

 

Re: Why does Mirtazapine cause Restless Legs Syndrome?

Posted by Lamdage22 on June 25, 2020, at 5:19:02

In reply to Re: Why does Mirtazapine cause Restless Legs Syndrome? » linkadge, posted by Skeletor on June 24, 2020, at 8:50:58

Kratom... no effect for me

 

Re: Why does Mirtazapine cause Restless Legs Syndrome? » undopaminergic

Posted by Skeletor on June 26, 2020, at 16:09:53

In reply to Re: Why does Mirtazapine cause Restless Legs Syndrome?, posted by undopaminergic on June 24, 2020, at 15:34:20

> >
> > BUT opioids induce histamine release, so it could just be a histamine thing?
>
> Some opioids, including morphine, induce the release of histamine from mast cells, which may lead to itching, but (AFAIK) they don't release histamine in the CNS.
>
> -undopaminergic
>

Does it need to cross the blood brain barrier or could it stimulate "it" directly in the legs?

 

Re: Why does Mirtazapine cause Restless Legs Syndrome?

Posted by undopaminergic on June 27, 2020, at 1:29:52

In reply to Re: Why does Mirtazapine cause Restless Legs Syndrome? » undopaminergic, posted by Skeletor on June 26, 2020, at 16:09:53

> > >
> > > BUT opioids induce histamine release, so it could just be a histamine thing?
> >
> > Some opioids, including morphine, induce the release of histamine from mast cells, which may lead to itching, but (AFAIK) they don't release histamine in the CNS.
> >
> > -undopaminergic
> >
>
> Does it need to cross the blood brain barrier or could it stimulate "it" directly in the legs?
>

Mast cells exist in peripheral tissues including, in particular, the skin, so it could affect the legs. However, this would more likely cause itching than RLS.

-undopaminergic

 

Re: Why does Mirtazapine cause Restless Legs Syndrome? » undopaminergic

Posted by Skeletor on June 29, 2020, at 13:26:38

In reply to Re: Why does Mirtazapine cause Restless Legs Syndrome?, posted by undopaminergic on June 27, 2020, at 1:29:52

Would make sense... a really complicated topic. It seems like until this day it remains a mystery.

 

Re: Why does Mirtazapine cause Restless Legs Syndrome?

Posted by creepy on August 18, 2020, at 2:44:28

In reply to Why does Mirtazapine cause Restless Legs Syndrome?, posted by Skeletor on June 19, 2020, at 13:32:58

I get worse RLS when I try to take antihistamines to sleep. Also when I take clonidine too late in the day or before bed. it wears off in 3 hours or so and the RLS is brutal. whether thats related to DA or NE I have no idea.
Dont drugs that promote excess serotonin tend to blunt dopamine as well? I would have to do a lot of digging to rememeber where I picked that up from and get you a good citation. dont have the energy =(
The drugs used for RLS are dopamine agonists or gabapentin. Havent tried any of those yet Im on enough drugs as it is.
Usually getting out of bed and doing 30-40 squats is enough to get the RLS to subside enough to sleep.


This is the end of the thread.


Show another thread

URL of post in thread:


Psycho-Babble Medication | Extras | FAQ


[dr. bob] Dr. Bob is Robert Hsiung, MD, bob@dr-bob.org

Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.