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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:
> "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.




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