WARNING: Pramipexole (Mirapex) withdrawal!

[Guide 4 Dummies]

I've been on Pramipexole for around 3 months. Even though it was very effective for SAD, it caused anhedonia that I couldn't bear taking it anymore. rocknroll714 also noticed the blunted hedonia when he was on this medication. It also made me less emotionally sensitive overall.

The use of D2/D3 dopaminergic agonists in Parkinson's disease (PD) may lead to pathological gambling. In a placebo-controlled double-blind study in healthy volunteers, we observed riskier choices in a lottery task after administration of the D3 receptor-preferring agonist pramipexole thus mimicking risk-taking behavior in PD. Moreover, we demonstrate decreased activation in the rostral basal ganglia and midbrain, key structures of the reward system, following unexpected high gains and therefore propose that pathological gambling in PD results from the need to seek higher rewards to overcome the blunted response in this system.

http://www.ncbi.nlm.nih.gov/pubmed/18575579

I tried to counteract it by caffeine + betahsitine + wellbutrin or nicotine to no avail. I quit Pramipexole cold-turkey on April 25th (26 days ago)*. The withdrawal syndrome is absolutely dreadful, and quitting cold-turkey turned out to be one of the three most traumatizing events I've experienced medication-wise. (The first being unintentional cold-turkey Alprazolam withdrawal, and the second was a bad reaction to selegiline resulting in depression and nightmares for 2 weeks).

Pramipexole withdrawal syndrome: (1.5 mg* / day, cold-turkey)
It consists of two stages (first stage confirmed by rocknroll714).

The first stage: (Began sometime during the first week, lasted for 2 days)
- Extremely elevated energy without increased motivation.
- Extremely exacerbated OCD.
- Anxiety, agitation and RLS.
- Hyperthermia and excessive sweating.
- Decreased need for sleep.
- Excessive appetite and thirst, no change in libido.
- Bodily euphoria.
- Derealization.
- Blurred vision.
- Compulsive behavior. (i.e. religiously watching TV despite the urge to stop)

The second stage: (Still going through it)
- Severe anhedonia.
- Severe depression (suicidal ideation, dysphoria, etc.) *Note: This is the first time in my life experiencing depression that severe, not even benzo withdrawal made me feel that depressed.
- Exacerbated OCD and ADD.
- Akathisia, RLS and agitation.
- Extreme anxiety.
- Headaches.
- Unpleasant, extremely vivid and violent dreams.
- Social isolation (due to social anhedonia).
- Lack of affect (coming off as mean and apathetic).
- Dramatically impaired concentration and memory (Loss of short and long-term memory).
- Insomnia/hypersomnia.
- Tinnitus and sound intolerance.
- Visual disturbance. (Static-like)
- Dizziness.
- Fatigue/tiredness.
- Orthostatic hypotension.

If you are quitting a dopamine agonist, please consider a very slow taper.

*Edited according to log files.

[mark555666]

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?

[Guide 4 Dummies]

Originally Posted by Freesix88

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?

Yes, tried it without memantine and it worked fine. As for my next plan, I have final exams in 2 days and I'm rendered unable to study due to depression, anhedonia and general cognitive impairment.

This is my 26th day since I dropped Pramipexole and I don't know how long this is going to last.* So I'm considering taking a low dose (0.25 mg) of Mirapex twice or thrice daily in order to halt the withdrawal or reduce it to a tolerable level, else I'll fail this year.

After the exams I'm planning on slow-taper Mirapex followed by slow-taper Alprazolam, and when I'm physically and mentally ready then I'll consider my next step.

*EDIT: It's not my 10th, it's actually my 26th according to the log files I keep on my computer. Oh god, didn't know I'm THAT cognitively impaired I lost track of time.

[Ehsan]

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.

[Guide 4 Dummies]

Took 0.125 mg an hour ago. Most of the withdrawal symptoms ended.

Considerable mood boost, severe depression became mild depression with lurking dysphoria and self-loathe. I notice memory and concentration improvement and general cognitive clarity. Anhedonia is still at the same level, though.

Not quite "back to normal", but I feel much better overall.

EDIT: Took another 0.125 mg, hopefully this will completely halt the withdrawal. Also, my dose was 1.5mg/day when I quit cold turkey according to the log files. Edited posts.

[Guide 4 Dummies]

Originally Posted by Ehsan

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.

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

26 days and withdrawal didn't cease in my case, it looks like it's going to take a long time to taper off, but 0.25mg seems to completely halt the withdrawal so I guess my dopaminergic system recovered somewhat since the original dose was 1.5mg/day according to log files and now I only need 0.25-0.75mg/day so this is okay.

[mark555666]

Originally Posted by Ehsan

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.

[crayzyMed]

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.

[Guide 4 Dummies]

Originally Posted by crayzyMed

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.

If it doesn't blunt hedonia and makes life seem extremely dull, then yeah I don't mind being on it.

[soaringfalcon11]

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??

[crayzyMed]

Originally Posted by soaringfalcon11

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.

[soaringfalcon11]

Originally Posted by crayzyMed

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!

[crayzyMed]

Originally Posted by soaringfalcon11

I was thinking about taking them while on cocaine!

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

[korey]

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.

[Guide 4 Dummies]

Originally Posted by korey

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.

I have to agree with him on that Pramipexole withdrawal is more brutal than Paxil and Effexor withdrawal. They are not even close.

The only thing I'd say was worse than Pramipexole withdrawal is cold-turkey chronic high dose alprazolam withdrawal since it made me extremely paranoid and I could have had a full blown psychotic episode or a seizure if I hadn't come back on it fast enough.

I've read an article that says dopamine agonist withdrawal is similar to cocaine withdrawal. However, I can't confirm that since I've never done cocaine.

Update:
Even though most of the withdrawal symptoms have subsided by taking 0.75mg/day, my memory hasn't recovered fully yet, and my ADD/SAD is extremely bad at the moment I only have a day left for final exam and I'm still procrastinating. It seems like D2 has been heavily downregulated.

[TouchyBoy]

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

[Ehsan]

Originally Posted by Guide 4 Dummies

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.

Originally Posted by crayzyMed

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.

[Guide 4 Dummies]

This form of pathological procrastination is terrible, and when I try and force myself to study, I'm extremely inattentive and my working memory is severely impaired.

I've taken 50mg of Sulpiride to selectively antagonize the presynaptic receptors. I don't think taking an antipsychotic is a good idea, but I had to do something. Anything. Hope it works..

[Guide 4 Dummies]

I'm pretty much back to normal. ADD and memory returned to normal levels. It feels so nice being able to study again. I've definitely made the right decision.

I've taken 0.5mg Pramipexole and 100mg Sulpiride. Which means I'm back to my original dosage of Pramipexole (1.5mg/day) with the addition of *Sulpiride (300-600mg/day) for selective presynaptic blockade.

I hate the fact that I'm taking an antipsychotic (risk of tardive dyskinsia), and I hate the fact that I'm back on my original dose of Pramipexole. It means that I've went through 1 month of agony unnecessarily, and it also means that there is a very, very bumpy road ahead withdrawal-wise.

I had to do something. I can't fail this year, I just can't. I'm glad that Sulpiride worked as expected.

Future plan:
After the exams are over (June, 17th), I'm going to taper off Sulpiride first thing. Then I'm going to slow-taper Alprazolam first, and then slow-taper Pramipexole second (or stay on it forever, or switch to **Trivastal).

As for exams, I'm going to take Meclofenoxate + Ginkgo Biloba + Ginseng + Gotu Kola + Caffeine + Nicotine, and make the best of the very limited time that is left.

*EDIT: Considering switching to Amisulpride for 5-HT7 antagonism, but need to research its effect on memory as 5-HT7 is highly expressed in the hippocampus and antagonizing this receptor could lead to spatial memory deficit.

** Okay Wesley, I may give this one a try. I'll have to research the long-term effect of its selective α2 antagonism. I don't have time to research now so maybe after exams.

[crayzyMed]

Originally Posted by TouchyBoy

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

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).