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Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 12 of 12. This is the beginning of the thread.
Posted by West on May 4, 2009, at 12:44:48
A course of mirtazapine was stopped short recently due to intense restless legs on the first night. I had crawling sensations and had to keep turning my legs round every 20 seconds or so. Taking a lot of clonazepam eventually did the job but it was my worst drug reaction since seroquel (same thing basically).
Since dopamine agonists are used to treat this problem, is this a biological pointer to 'low dopamine' or is this too simplistic a theory?
How common is this?
Posted by Phillipa on May 4, 2009, at 12:58:00
In reply to Mirtazapine and RLS, posted by West on May 4, 2009, at 12:44:48
You know sometimes it feels like bugs crawling in my legs and they twitch. But from what I've read that isn't RLS. Don't you kick and stuff like that? Phillipa
Posted by West on May 4, 2009, at 13:13:59
In reply to Mirtazapine and RLS, posted by West on May 4, 2009, at 12:44:48
No they ached badly and i couldn't sit them still. They felt detached from my body, i wanted to chop them off it was so bad.
Posted by sowhysosad on May 4, 2009, at 14:43:51
In reply to Re: Mirtazapine and RLS, posted by West on May 4, 2009, at 13:13:59
> No they ached badly and i couldn't sit them still. They felt detached from my body, i wanted to chop them off it was so bad.
Sounds more like akathisia West.
I had some weird movement stuff on mirt, but mostly low grade problems like myoclonic jerks and little twitches that were probably down to serotonin. That said, my dopamine was already depleted by some bad SSRI experiences shortly before, so maybe that contributed.
Previously I could've sworn mirt had no effect on my serotonin levels at all, but since I've started taking 5-HTP I've been getting identical minor movement stuff going on.
Posted by West on May 4, 2009, at 16:03:56
In reply to Re: Mirtazapine and RLS, posted by sowhysosad on May 4, 2009, at 14:43:51
I thought that was what it could be, but since it was just in the legs i think it's more likely to be rls. Akithisia is a whole body feeling and of not being able to control it.
Of interest on mirtazapine: ken gillman seems unconvinced it has any significant serotonergic action at all, claiming serotonin syndrome is almost impossible to induce even at uber overdoses; there is however at least one documented case of SS i know of in somebody taking it alone and with nothing else on board.
How do you find it in comparison to the SSRIs in regards to your depression? I imagine there's less apathy involved since mirt increases noradrenergic and (in theory) dopaminergic tone. I'm pretty much resigned to taking an ssri for life since i rapidly decline without it.
I have never heard of dopamine depletion with SSRIs, that does not sound good at all.
Posted by sowhysosad on May 4, 2009, at 18:08:35
In reply to Re: Mirtazapine and RLS » sowhysosad, posted by West on May 4, 2009, at 16:03:56
> I thought that was what it could be, but since it was just in the legs i think it's more likely to be rls. Akithisia is a whole body feeling and of not being able to control it.
I've read theories about region-specific akathisias - eg. some speculate SSRI-induced bruxism is a variety of it.
> Of interest on mirtazapine: ken gillman seems unconvinced it has any significant serotonergic action at all, claiming serotonin syndrome is almost impossible to induce even at uber overdoses; there is however at least one documented case of SS i know of in somebody taking it alone and with nothing else on board.
Yeah, I was initially with Ken Gillman on that one as I didn't think I was getting a serotonergic effect. That said, as I mentioned earlier, I now realise I probably had some mild serotonin-related side effects.
Maybe mirt just wasn't all that powerful for me when it came to serotonin, or my receptors were fried or something. Or perhaps the 5HT2A/C blockade made it feel different to SSRI's.
> How do you find it in comparison to the SSRIs in regards to your depression? I imagine there's less apathy involved since mirt increases noradrenergic and (in theory) dopaminergic tone. I'm pretty much resigned to taking an ssri for life since i rapidly decline without it.
It did next to nothing for my depression but, to be fair, I've since realised that noradrenergic meds just don't seem to work for me. However, it didn't seem to boost my noradrenaline as much as imipramine, the med I moved on to next. Imipramine made me very edgy and anxious at times.
As far as apathy is concerned, you may find the heavy sedation mirt induces might actually outweigh the noradrenergic benefits. For some it gets better the longer they're on it and the higher the dose, but others have a long-term issue with the sedation (15mg mirt = 10mg diazepam IIRC).
I don't think it had any effect on dopamine at all. Since quitting meds and switching to a dopamine-boosting supplement (helped along by some other dopaminergics like nicotine and codeine) my depression's got way better. There was no danger whatsoever of that happening with mirt, and I just couldn't "feel" any dopamine.
Posted by West on May 4, 2009, at 18:23:37
In reply to Re: Mirtazapine and RLS » West, posted by sowhysosad on May 4, 2009, at 18:08:35
Cool, and interesting. Can i ask, were you severe? What about the codeine, is that prescribed? (he asks, looking a bit doubtful). I'm pretty sure i'll pass up 'taz presently but good luck. I've got some tramadol on the way which i'm feeling entirely unprepared for.
Posted by Phillipa on May 4, 2009, at 19:58:53
In reply to Re: Mirtazapine and RLS » West, posted by sowhysosad on May 4, 2009, at 18:08:35
Seriously 15mg of remeron was nothing like l0mg of valium for me. The remeron was worthless for me. Phillipa
Posted by sowhysosad on May 4, 2009, at 21:14:08
In reply to Re: Mirtazapine and RLS, posted by West on May 4, 2009, at 18:23:37
> Cool, and interesting. Can i ask, were you severe?
Yeah, it was a severe and chronic depression. It was a kind of rebound depression after suffering akathisia on sertraline, and unlike any depression I had before. There was a definite lingering dopamine issue after the akathisia, which makes sense given SSRI-induced akathisia is supposedly caused by overly high serotonin which in turn causes dopamine depletion.
I also had a comorbid movement disorder in my jaw, doubtless also as a result of the dopamine depletion thing (although I'd previously had some milder symptoms on Cipralex). Misery surrounding that was perpetuating the depression and meds seemed to make the condition worse.
> What about the codeine, is that prescribed? (he asks, looking a bit doubtful).
I used it in the 2 darkest days after withdrawing from imipramine, combining 2 OTC meds so as not to OD on paracetamol or ibuprofen. It had an immediate antidepressant effect.
It also had the unexpected side effect of dramatically improving my movement disorder, which confirmed my theory about depleted dopamine (apparently codeine causes dopamine release through a GABA-mediated mechanism).
[Just a brief aside: my NHS neuro disagrees with every piece of research I've read on codeine and dopamine and claims the former inhibits the latter. He originally suggested trying an atypical antipsychotic to block D2 receptors. I finally convinced him dopamine depletion was actually the problem, and he then suggested trying Levodopa in the future. Errrr....no thanks.]
> I'm pretty sure i'll pass up 'taz presently but good luck.
A lot of people in another thread here said it did nothing for their severe depression, so perhaps a good move.
>I've got some tramadol on the way which i'm feeling entirely unprepared for.
Let us know how you get on.
Posted by sowhysosad on May 4, 2009, at 21:18:10
In reply to Re: Mirtazapine and RLS » sowhysosad, posted by Phillipa on May 4, 2009, at 19:58:53
I suppose the mechanism of the sedative effects are different for each drug so they won't necessarily "feel" the same for everyone, but it's a general rule of thumb I once read (on Ken Gillman's site IIRC).
> Seriously 15mg of remeron was nothing like l0mg of valium for me. The remeron was worthless for me. Phillipa
Posted by metric on May 6, 2009, at 16:12:12
In reply to Mirtazapine and RLS, posted by West on May 4, 2009, at 12:44:48
> A course of mirtazapine was stopped short recently due to intense restless legs on the first night. I had crawling sensations and had to keep turning my legs round every 20 seconds or so. Taking a lot of clonazepam eventually did the job but it was my worst drug reaction since seroquel (same thing basically).
> Since dopamine agonists are used to treat this problem, is this a biological pointer to 'low dopamine' or is this too simplistic a theory?
I think it's more complicated than that, since dopamine could be modulating other systems downstream. It could also be a matter of relative dominance of one system over another. For example, disruption of the cholinergic-dopaminergic balance is a key factor in movement disorders such as Parkinson's disease (which is why patients with Parkinson's disease are often given anticholinergic drugs).* However, it seems sufficient to reduce dopaminergic activity in certain areas of the brain.
> How common is this?
I don't know. Both mirtazapine (6-aza-mianserin) and its chemical cousin mianserin are known to induce RLS on occasion.
I had a similar experience when combining mirtazapine with duloxetine. I thought it was noradrenergically mediated, given the pharmacology of the two drugs. It went away after a few nights. How much mirtazapine did you take? Reducing the dose and then increasing it gradually might help.
BTW, RLS is sort of a misnomer as the motor impulses aren't necessarily restricted to the legs.
* You might find the following paper of interest:
Tzavara, E.T. et al. "M4 muscarinic receptors regulate the dynamics of cholinergic and dopaminergic neurotransmission: relevance to the pathophysiology and treatment of related central nervous system pathologies." FASEB J. 04-1575fje(2004).doi:10.1096/fj.04-1575fje
http://www.fasebj.org/cgi/content/abstract/04-1575fjev1I'd like to emphasize that I have no special knowledge of movement disorders.
Posted by desolationrower on May 13, 2009, at 3:08:52
In reply to Re: Mirtazapine and RLS » West, posted by metric on May 6, 2009, at 16:12:12
alpha2 antagonists increase dopamine, i think throughout the brain. might be something else
-d/r
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