# WARNING: Pramipexole (Mirapex) withdrawal!



## Guide 4 Dummies (Nov 2, 2009)

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## mark555666 (May 1, 2008)

Too bad about it induced depression. It was working so well for you. Did you also try it without memantine?

What is you next plan?


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## Ehsan (Mar 21, 2009)

i'd experienced almost similar withdrawal syndrome after quitting L-Dopa + memantine + selegiline before.
it worked well for my SAD but the withdrawal syndrome was such bad that reversed all the improvements i'd made.

there is not any doubt that dopaminergic system has a pivotal role in SAD.
dopaminergics work great for SAD in short terms, but i think using dopamine agonists is not a good idea to combat SAD.
they downregulate dopamine receptors and so have more negative effects on SAD after withdrawal than positive effects one see with their use.

maybe we should find some way to upregulte dopamine receptors without direct use of dopaminergics instead of using dopamine agonists.


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## mark555666 (May 1, 2008)

Ehsan said:


> maybe we should find some way to upregulte dopamine receptors without direct use of dopaminergics instead of using dopamine agonists.


Hmm I don't think it's possible to up-regulate dopamine receptors 24/7. Unless we can find a way to avoid homeostasis. So dopamine agonists probably won't work but CrazyMed has hopes in lisuride so maybe that one will work but I still have my doubts. So what's left? Anti depressants that inhibits and/or release dopamine and the common stimulants.
Unless we can find a way to shoot dopamine receptors in the brain (this sounds futuristic lol but they did it with rats with success) I still think stimulants are the best with memantine (with breaks) otherwise homeostasis strikes again. 
I'm slightly drunk so excuse me for this weird post. lol.


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## crayzyMed (Nov 2, 2006)

> So dopamine agonists probably won't work


If they have a bad withdrawal doesnt mean they dont work, both ehsan and guide4dummies didnt report a decline in effectiveness.

If i plan to stay on a med forever i dont mind it having a bad withdrawal.


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## soaringfalcon11 (Jun 7, 2009)

Wow, that's pretty cool you were using a dopamine agonist! I would like to try that sometime, though not for SA, for fun! And yeah, withdrawl would definitely be expected, as your dopamine recoptors have deregulaed...dopamine defencency.

Luckly the brain is an amazing organ and you will eventually feel better. I wonder if opiates would help the withdrawls any?

BTW what is hedonia??


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## crayzyMed (Nov 2, 2006)

soaringfalcon11 said:


> Wow, that's pretty cool you were using a dopamine agonist! I would like to try that sometime, though not for SA, for fun! And yeah, withdrawl would definitely be expected, as your dopamine recoptors have deregulaed...dopamine defencency.
> 
> Luckly the brain is an amazing organ and you will eventually feel better. I wonder if opiates would help the withdrawls any?
> 
> BTW what is hedonia??


lol, blunted hedonia is marks saying of anhedonia (hedonia being the opposite of anhedonia).

Dopamine agonists for fun? do you mean to have sex on? As they wont be much fun on their own, pramipexole would cause anxiety in some without 5HT1A agonism and anhedonia.


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## soaringfalcon11 (Jun 7, 2009)

crayzyMed said:


> lol, blunted hedonia is marks saying of anhedonia (hedonia being the opposite of anhedonia).
> 
> Dopamine agonists for fun? do you mean to have sex on? As they wont be much fun on their own, pramipexole would cause anxiety and anhedonia.


I was thinking about taking them while on cocaine!


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## crayzyMed (Nov 2, 2006)

soaringfalcon11 said:


> I was thinking about taking them while on cocaine!


lol, i can guarantee that it wont be a pleasant experience


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## korey (Apr 25, 2006)

On another forum I go to that deals with psych meds (crazymeds.us), one or more of the moderators has stated a few times in various threads that dopamine agonist (ie Mirapex, Requip, etc.) withdrawal is like, 100x worse than Effexor withdrawal. And since I've been through Effexor withdrawal and know how unpleasant it is, that makes me really not want to mess with dopamine agonists. :afr


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## Ehsan (Mar 21, 2009)

Guide 4 Dummies said:


> How long were you on this combo and how long did the withdrawal syndrome last?


one month.
withdrawal syndrome including depression,anxiety,headache, lack of energy and fatigue persisted for about 1 month. however i still feel my SAD is worse than before its use.



crayzyMed said:


> If they have a bad withdrawal doesnt mean they dont work, both ehsan and guide4dummies didnt report a decline in effectiveness.
> If i plan to stay on a med forever i dont mind it having a bad withdrawal.


i don't like meds that stop working or worsen the problem after discontinuation. in my case using dopamine agonists worsened SAD after discontinuation and it isn't weird.

anyway, stratial dopamine binding affinity is lower than normal in SAD(maybe a genetic problem) and it seems using dopamine agonists and releasers are the only effective ways now.

i read somewhere that froskolin upregulates dopamine d2 receptors in striatum of RATs but i don't know if it is of clinical significance or not.


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## crayzyMed (Nov 2, 2006)

TouchyBoy said:


> I thought that the use of memantine also prevented from withdrawal symptoms  ... I was too confident


It could (if withdrawal is because of reduced D2 density and glutamate hyperactivity), mark wasnt on memantine the last few weeks and when he was he underdosed (he was only on it for a short time tough).


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## crayzyMed (Nov 2, 2006)

Ehsan said:


> one month.
> withdrawal syndrome including depression,anxiety,headache, lack of energy and fatigue persisted for about 1 month. however i still feel my SAD is worse than before its use.
> 
> i don't like meds that stop working or worsen the problem after discontinuation. in my case using dopamine agonists worsened SAD after discontinuation and it isn't weird.
> ...


I think NMDA antagonists are the most effective option to upregulate dopamine receptors, maybe try a differend one then memantine as you didnt like it?

That said, taking short breaks (for example 2 days off your med every week) will have a huge benefit on the potential downregulation, with LDOPA this can be done, with dopamine agonists probably not due to the autoreceptors.


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## Ehsan (Mar 21, 2009)

i disagree.
i think memantine should have a negative role here which is ignored.
maybe memantine inhibits rapid change in dopamine receptors' count after discontinuation of dopamine agonist(upregulation) through NMDA blockade(reduces neuro-plasticity).
memantine has a very long half-life(80-100hours) and will remain in blood for a very long time.
this can delay the recovery of dopaminergic system.
in fact, memantine will decelerate downregulation of dopamine receptors but also decelerate the process of upregulation(recovery).


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## crayzyMed (Nov 2, 2006)

Ehsan said:


> i disagree.
> i think memantine should have a negative role here which is ignored.
> maybe memantine inhibits rapid change in dopamine receptors' count after discontinuation of dopamine agonist(upregulation) through NMDA blockade.
> memantine has a very long half-life(80-100hours) and will remain in blood for a very long time.
> ...


This doesnt appear to be the case, as anecdotally tolerance to dopaminergic drugs seems recovers faster with memantine then without. NMDA antagonism upregulates D2 but doesnt downregulate it, a hyperactive glutamine system downregulates it. Memantine doesnt freeze homeostasis, it just that nmda antagonism has a positive effect on the binding of several receptors.


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## crayzyMed (Nov 2, 2006)

> Memantine attenuates the increase in striatal preproenkephalin mRNA expression and development of haloperidol-induced persistent oral dyskinesias in rats
> 
> Ole A. Andreassena, , , Jo Waageb, Bente Finsenc and Hugo A. Jørgensenb
> a The Research Section, Department of Psychiatry, University of Oslo and Ullevål University Hospital, Kirkeveien 166, 0407, Oslo, Norway
> ...


Memantine to the rescue?

EIther way, i think that only postsynatpic antagonism of dopamine receptors is a problem, the reason you dont see a dose relationship is because sulpiride is practically never prescribed in doses that only block the presynaptic receptors. I do not think low doses of sulpiride or amisulpride cause TD.


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## Lizzie Z (Jan 8, 2011)

*Mirapex sucks*

I have been on Maripex since 1993 for restless leg syndrome. It has now to the point that the inside of my legs and arms feel like they are going to explode. I also suffer from Lupus and fybromylgia. I was told by my specialist that it time to go off Mirapex, so I have b een decreasing it slowly and for the past two days I have gone off totally. I can tell you it has definitely helped with the stiffness of my arms and legs, but not totally yet. As you can tell I am wide awake (4:10 am) and have been for the past two nights. I hope someone can tell me how long the suffering of withdrawal will take with sthis evil medication. My restless legs are acting up of course, but is better than being in sever pain. Any comments?


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## peaceandlove09 (Aug 10, 2010)

Guide 4 Dummies said:


> My severe withdrawal case is very rare. You would probably get 2-weeks tops. It may get very tolerable after only 1 week.
> 
> My withdrawal lasted for 5 months and I had to take other medications to become better. Now it's 95% over and I'm still getting better, which I'm very thankful for.


Do you think it's OK to take Mirapex recreationally for a libido boost? Maybe a handful of times per year?

I ordered some Mirapex online (30 days worth) and i am debating if I want to just junk it, or use it very sparingly. I might throw out most of it, but keep say 10 tablets to use recreationally for libido


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## breeetie (Nov 16, 2014)

Ten weeks ago, my RLS was getting out of control. My physician added Hortizant, a time release Gabapentin. When added, I experienced augmentation, and the RLS was so severe that I found myself taking anything that I could find to stop the torture. I consulted with him the next day, and I started titrating the Pramipexole, stopping the Horizant, and adding Cloznazepam. Initially, I passed out and severely hit my head. Then came the chills, hot flashes, nausea and vomiting and hand tremors. Depression followed, and was so severe that I was near crisis and narrowly escaped having to be admitted to the hospital. I left secure and safe in my loving home, but traveled to stay with a daughter for change of pace. I am now under the care of a Psychiatrist, as well as a Psychologist, which both have a co-pay. Antidepressants(more $) were started but it took three weeks to feel better. The depression came on quickly without provocation, and produced crying until exhaustion, and falling asleep numerous times during the day.
I had been diagnosed with lymphedema and received therapy. Insurance paid for the leg boots that filled with air to help pump the fluid from my lower legs, and paid for the pump. Ins did not cover the compression garments that cost $200 and last about one year. I also was diagnosed with neuropathy of the lower legs, confirmed with nerve conduction tests. My feet burned, and my legs felt burning and pin prick-like feelings. Once off of Pramipexole, the swelling in my legs is almost gone, and the neuropathy feels as if it too is gone, but the nerve conduction tests have not been repeated. I am now free of all symptoms with the exception of hand tremors and depression. It is still brought on in a heartbeat by anything disturbing, no matter how minor. After 10 weeks of withdrawing, it is inconceivable why anyone would accept being put on this medication if their physician explained all information to them. I had numerous physicians over the years due to moving, so the medication was continued with each new doctor and increased by some until a max of 3 mg per evening. I have and am still going through hell, but the RLS is almost completely under control with Horizant, Clonazepam, and additional Gabapentin. Would like to hear from others who have gone through similar circumstances, and what medications have eased their RLS.


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