86 replies to this topic

[VespeneGas]

By way of introduction, this is what FunkOdyssey, who I have to thank for turning me on to this drug's existence, has to say about it:

I think I hit a gold mine with pramipexole. It probably deserves it own thread. Its neuroprotective, neurotrophic, an antidepressant, anti-anhedonic, anxiolytic, improves motivation/initiative, boosts libido and reduces refractory time. It may be of specific value in Lyme as it prevents lipopolysaccharide-induced dopaminergic cell death. It may be useful as a general anti-aging drug, considering that an adult loses 5-10% of their dopaminergic neurons every decade and pramipexole may have the power to halt or reverse this loss.

A quick perusal of pubmed pulled up the following studies. How have I never heard of this drug before, much less tried it? It looks like a very promising drug for those of us who don't respond well to SSRI's and won't accept the risks and sides of long-term amphetamine/methylphenidate use.

[The Role of Low-Dose Pramipexole in the Treatment of Treatment-Resistant Bipolar Depression: A Case Report.]
[Article in Turkish]

Akdenız F, Aldemır E, Vahıp S. Despite a wide range of various drugs, a significant proportion of depressed bipolar patients fail to respond to the treatment strategies. Novel theraupetics for bipolar depression are needed. Preliminary studies suggest that pramipexole a dopaminergic agent that has been used in the treatment of Parkinson's disease and restless leg syndrome may have antidepressant properties in unipolar and bipolar depressed patients as well as neurotrophic properties. The optimal antidepressant daily dose of pramipexole is not known. It has been suggested to be used between 0.125 to 9.0 mg/day. In double blind placebo controlled bipolar depression treatment studies, the average daily dose of pramipexole was 1.7 mg. Manic switches have been reported with depressive subjects and with subjects without any mental disorders. We report two cases of treatment resistant bipolar depression. Despite different treatment strategies and treatment adherence, the patients did not give optimal response to the treatments and continue to experience depressive relapses. They have been treated with low dose (0.5-0.75 mg/day) pramipexole augmentation successfully. The severity and the duration of the depressive episodes were decreased. No serious adverse event has been reported with pramipexole during the maintenance treatment.

PMID: 19306131 [PubMed - as supplied by publisher

Effects of the dopamine agonist pramipexole on depression, anhedonia and motor functioning in Parkinson's disease.
Lemke MR, Brecht HM, Koester J, Reichmann H. Center of Psychiatry and Neurology, Rhine Clinic Bonn, Germany. mr.lemke@lvr.de

Depression affects approximately 45% of all patients with Parkinson's disease, reduces quality of live independent of motor symptoms and seems to be underrated and undertreated. Pramipexole shows D(3)- versus D(2)-receptor preference at cortico-frontal dopamine receptors and neurotrophic effects which seem to relate to its antidepressant and anti-anhedonic properties in Parkinson's disease and bipolar depression found in controlled studies. In the present study, effects of pramipexole were investigated under routine clinical conditions. Anhedonia was measured in patients with Parkinson's disease (n=657) using the self-rated Snaith-Hamilton-Pleasure-Scale (SHAPS-D), depression was assessed by the observer-rated Short-Parkinson's-Evaluation Scale (SPES). Anhedonia was present in 45.7% of all patients and in 79.7% of the depressed patients with Parkinson's disease. Mild depression was present in 47%, moderate to severe depression in 22% of the patients. At the end of the study period of 9 weeks on an average, the mean dosage of pramipexole was 1.0+/-0.6 mg/d (range 0.3 to 4.2). Frequency of depression (moderate to severe: 6.8%, mild: 37.6%) and anhedonia (25.5%) as well as motor deficits were significantly reduced during treatment with pramipexole. Drop-outs due to adverse events occurred in 3.5%. Future studies should investigate specificity of anti-anhedonic and antidepressive properties of pramipexole.

PMID: 16814808 [PubMed - indexed for MEDLINE

Pramipexole and pergolide in the treatment of depression in Parkinson's disease: a national multicentre prospective randomized study.
Rektorová I, Rektor I, Bares M, Dostál V, Ehler E, Fanfrdlová Z, Fiedler J, Klajblová H, Kulist'ák P, Ressner P, Svátová J, Urbánek K, Velísková J. First Department of Neurology, Masaryk University, St Anne's Teaching Hospital, Brno, Czech Republic. irena.rektorova@fnusa.cz

An 8-month multicentre prospective randomized study aimed at comparing the effects of dopamine receptor agonists pramipexole (PPX; Mirapexin) and pergolide (PRG; Permax) as add-on to L-dopa therapy on depression [Montgomery and Asberg Depression Rating Scale (MADRS)] in 41 non-demented patients (25 men, 16 women) suffering from both mild or moderate depression and advanced Parkinson's disease (PD). The assessment was performed by a blinded independent observer. Motor symptoms (UPDRS III), motor complications (UPDRS IV), activities of daily living (UPDRS II and VI) and depressive symptoms as measured by Self - Rating Depression Scale by Zung were evaluated in an open-label design. The average value of Zung scores decreased significantly in both groups with no statistical difference between both groups. A significant decrease in the average value of MADRS scores was present only in the PPX group. The average UPDRS scores decreased significantly with no statistical difference between both groups at the comparable average total daily dose of both preparations. In both cases, the total daily dose of L-dopa decreased significantly but the decrease was statistically more pronounced in the PRG group. Our results demonstrate the antidepressant effect of PPX in patients with PD while we can't make any conclusions with regard to antidepressant effect of PRG.

PMID: 12823492 [PubMed - indexed for MEDLINE

Pramipexole has astrocyte-mediated neuroprotective effects against lactacystin toxicity.
Imamura K, Takeshima T, Nakaso K, Ito S, Nakashima K. Department of Neurology, Institute of Neurological Sciences, Tottori University, Faculty of Medicine, Yonago, Tottori, Japan. imamurakeiko@nifty.com

Pramipexole, a dopamine D2/D3 receptor agonist used in the treatment of Parkinson's disease, has been reported to have neuroprotective potential. We investigated the effect of pramipexole against cell death induced by a proteasome inhibitor, lactacystin, using primary mecencephalic neuronal cultures and SH-SY5Y cells. In E14 rat primary mesencephalic cultures, the number of surviving tyrosine hydroxylase (TH)-positive neurons and microtubule associated protein 2 (MAP2)-positive neurons was decreased by exposure to 1-5 microM lactacystin in a dose-dependent manner. Pretreatment with 100 microM pramipexole rescued TH-positive neurons and MAP2-positive neurons from the toxicity of lactacystin. The protective effect of pramipexole was not selective for TH-positive dopaminergic neurons. However, the treatment with 100 microM pramipexole did not protect SH-SY5Y cells against lactacystin-induced cell toxicity and proteasome dysfunction. We hypothesized that the protective effect of pramipexole against the lactacystin-toxicity was not direct but a secondary effect mediated by astrocytes. Therefore, we investigated the efficacy of conditioned medium collected from mecencephalic astrocytes treated with pramipexole. The conditioned medium increased the viability of SH-SY5Y cells against the toxicity of lactacystin. Pramipexole increased the levels of brain derived neurotrophic factor (BDNF) in the conditioned medium of astrocyte cultures. These protective effects were not significantly inhibited by dopamine D2 or D3 receptor antagonists. We demonstrated that pramipexole had the protective effect against lactacystin toxicity, mediated by a neurotrophic effect of astrocyte-produced factors including BDNF.

PMID: 18555604 [PubMed - indexed for MEDLINE

Pramipexole in psychiatry: a systematic review of the literature.
Aiken CB. Department of Psychiatry, Wake Forest University School of Medicine, Winston-Salem, NC, USA. christopher.aiken.med.99@aya.yale.edu

OBJECTIVE: To assess the risks and benefits of pramipexole in psychiatric populations. DATA SOURCES: A PubMed search was performed using the keywords pramipexole and ropinirole, which identified 500 articles. STUDY SELECTION: All clinical studies in psychiatric populations were included in the primary review (24 articles). Studies involving other populations were then reviewed to evaluate potential risks and benefits not identified in the psychiatric studies. DATA EXTRACTION: Effect sizes were calculated from controlled studies. Rates of intolerable side effects and manic switching were estimated by pooled analysis of controlled and uncontrolled studies. DATA SYNTHESIS: Pramipexole has a large effect size (0.6-1.1) in the treatment of both bipolar and unipolar depression with a low short-term rate of manic switching in bipolar patients (1% mania, 5% hypomania). The pooled discontinuation rate for all reasons was 9%. Pramipexole is neuroprotective and exerts beneficial effects on sleep architecture. Pramipexole is associated with 3 rare but serious side effects: sleep attacks, which have only occurred in Parkinson's disease; compulsive behaviors and pathologic gambling, which have occurred in Parkinson's disease and restless legs syndrome; and psychosis, which has occurred in both psychiatric and neurologic populations. CONCLUSIONS: Pramipexole is an important therapeutic option for treatment-resistant bipolar and unipolar depression; further studies are warranted to evaluate its safety in psychiatric patients.

PMID: 17854248 [PubMed - indexed for MEDLINE]

Any more studies are welcome. I am also VERY interested to hear people's experiences with this stuff, because some things look good on paper but turn out to be meh in practice. According to wikipedia,
common sides include:

• Dizziness, lightheadedness, or fainting, especially when standing up (orthostatic hypotension)
• Drowsiness
• Hallucinations (seeing, hearing, or feeling things that are not there)
• Weight gain
• Weight loss
• Nausea
• Trouble in sleeping
• Twitching, twisting, or other unusual body movements
• Unusual tiredness or weakness

Ok, I'll shut up now. Discuss!

[FunkOdyssey]

Before discussion commences, you may want to review recent discussion that has already taken place at M&M on the topic, and then we can build on that:

Pramipexole: Incredible Promise

They've already done an excellent job dissecting the pharmacology of the drug, in particular Ex Dubio deserves credit there.

Edited by FunkOdyssey, 08 April 2009 - 08:05 PM.

[hullcrush]

Took my first dose ever last night @ .0612 mg. Can't say I had any side effects. Was still pretty tired when I woke up today. Improved with caffeine. Will be boosting my dosage to .125 mg tonight. I didn't have any nightmares. I am taking it because my plasma dopamine is low and my AM cortisol is probably low.

Mirapex has the neuroendocrine effect of raising ACTH and blocking norepinephrine, and reducing PRL while simultaneously raising GH.
Endocrinology of Pramipexole

This is an extremely unique functionality. ACTH is usually raised by the adrenergic systems (norepinephrine), and prolactin is often a co-factor in GH release.

My only concern is fatigue exacerbation and the imbedded sulfur atom. The fatigue is probably due to lowered basal metabolic rate--- dopamine suppresses thyroid hormone release to an extent.

If failed; drugs with similar cortisol MOAs are interesting: night hydrocortisone, 5-HTP, arginine, clonidine (reverses suppressed cortisol in special individuals). None have the benefit of increased dopamine though! They all reduce the levels IIRC.

Edit: Terrible sentence structure.
Moving myself to M&M nothing to see here folks...

Edited by hullcrush, 08 April 2009 - 08:39 PM.

[FunkOdyssey]

The fatigue is due to temporary reductions in firing rate of NE and DA neurons. This effect is transient and disappears with continued use as autoreceptors are desensitized. This is discussed in more detail in the link I provided above.

Edited by FunkOdyssey, 08 April 2009 - 08:28 PM.

[hullcrush]

The fatigue is due to temporary reductions in firing rate of NE and DA neurons. This effect is transient and disappears with continued use as autoreceptors are desensitized. This is discussed in more detail in the link I provided above.

Thanks funk, hoping it will get better.

[StrangeAeons]

I appreciate this being brought up, and I'm definitely going to take this into consideration.
I am currently pending parenteral iron replacement therapy, and its level of efficacy in treating my refractory mood should clue me into how far back the deficiency goes. If it stems all the way back to early childhood, I'll be in need of some type of dopaminergic in an attempt to counter the dopamine receptor damage.
That said, the possible risk of valve fibrosis is pretty scary. For me it might come down to a quality vs. quantity of life judgment, but for the average life extensionist I should think even a hint of this should be discouraging.
While we're on the subject of dopaminergics, I'm also considering low doses of the antipsychotic amisulpride. It appears to target autoreceptors preferentially at low doses, giving it somewhat of a paradoxical profile. I'm not sure if I can brag about its efficacy in Lyme or as a neuroprotectant, but it seems to have a pretty solid antidepressant and anti-anhedonic profile.

[FunkOdyssey]

The non-ergot dopamine agonists do not cause valve fibrosis, I posted a recent study to that effect in the thread on M&M.

Now, amisulpride on the other hand has risks, albiet aesthetic, that I would not be willing to take. It sends prolactin through the roof, and as a result a significant fraction of amisulpride users develop gynecomastia.

Edited by FunkOdyssey, 09 April 2009 - 06:07 AM.

[VespeneGas]

From the M&M forums:

Sustained administration of pramipexole modifies the spontaneous firing of dopamine, norepinephrine, and serotonin neurons in the rat brain.
Chernoloz O, El Mansari M, Blier P. Institute of Mental Health Research, University of Ottawa, Ottawa, Ontario, Canada. Olga.Chernoloz@rohcg.on.ca

Pramipexole (PPX) is a D(2)/D(3) receptor agonist that has been shown to be effective in the treatment of depression. Serotonin (5-HT), norepinephrine (NE) and dopamine (DA) systems are known to be involved in the pathophysiology and treatment of depression. Due to reciprocal interactions between these neuronal systems, drugs selectively targeting one system-specific receptor can indirectly modify the firing activity of neurons that contribute to firing patterns in systems that operate via different neurotransmitters. It was thus hypothesized that PPX would alter the firing rate of DA, NE and 5-HT neurons. To test this hypothesis, electrophysiological experiments were carried out in anesthetized rats. Subcutaneously implanted osmotic minipumps delivered PPX at a dose of 1 mg/kg per day for 2 or 14 days. After a 2-day treatment with PPX the spontaneous neuronal firing of DA neurons was decreased by 40%, NE neuronal firing by 33% and the firing rate of 5-HT neurons remained unaltered. After 14 days of PPX treatment, the firing rate of DA had recovered as well as that of NE, whereas the firing rate of 5-HT neurons was increased by 38%. It was also observed that sustained PPX administration produced desensitization of D(2)/D(3) and 5-HT(1A) cell body autoreceptors, as well as a decrease in sensitivity of alpha(2)-adrenergic cell body autoreceptors. These adaptive changes are implicated in long-term firing rate adaptations of DA, NE and 5-HT neurons after prolonged PPX administration. In conclusion, the therapeutic action of PPX in depression might be attributed to increased DA and 5-HT neurotransmission.

PMID: 18688211 [PubMed - indexed for MEDLINE]

Soooo... ultimately, pramipexole's mechanism is serotonergic (through the increased firing of 5-HT neurons)? Or is it also ultimately dopaminergic because dopamine firing recovers after 14 days AND the agonist is stimulating dopamine receptors? There would have to be some sort of increase in dopaminergic activity long term if the increased libido and anhedonia/initiation etc persisted. Also, what do y'all think are the implications of it's stimulation of neurogenesis in the substantia nigra? SSRI's are known to trigger neurogenesis in the hippocampus... I wonder if growth of new dopaminergic neurons might be a long term answer to depression, anhedonia, low libido, etc.

@FunkOdyssey thanks for the information! I have a couple questions.
1. How close are you to titration (a dose that you plan to sustain for months) or are you figuring that out as you go?
2. What are the primary effects that you attribute to pramipexole so far? Also, I remember you mentioning that you take memantine... are you on any other psychoactive drugs/supplements?
3. How bad are the sides? are you getting a lot of drowsiness? Drowsiness + motivation would be weird

[FunkOdyssey]

Soooo... ultimately, pramipexole's mechanism is serotonergic (through the increased firing of 5-HT neurons)? Or is it also ultimately dopaminergic because dopamine firing recovers after 14 days AND the agonist is stimulating dopamine receptors?

Yes and yes. Both 5-HT and DA neurotransmission are enhanced as the study concludes.

I wonder if growth of new dopaminergic neurons might be a long term answer to depression, anhedonia, low libido, etc.

That seems to be a hopeful possibility.

1. How close are you to titration (a dose that you plan to sustain for months) or are you figuring that out as you go?
2. What are the primary effects that you attribute to pramipexole so far? Also, I remember you mentioning that you take memantine... are you on any other psychoactive drugs/supplements?
3. How bad are the sides? are you getting a lot of drowsiness? Drowsiness + motivation would be weird

1. I'm at 1.125mg now, this is only my second day at that dose. I started last Thursday with .125mg x3 daily and have been raising the dose every 2-3 days. This is not recommended -- you should wait 5-7 days before increasing the dose. I am probably going to go up one more time to 1.5mg. I was initially planning to settle in at either 1.125mg or 1.5mg, but the careful and time-consuming pill splitting required to take .375mg three times daily is getting old quickly.

I'm going to assert myself and answer your questions in a different order of my own choosing (dopamine agonism talking? lol)

3. The sides are annoying and are present with each dose increase. They include drowsiness, spaceyness / loopeyness, orthostatic hypotension, and a trend toward constipation. Each day I remain at the same dose, the side effects decline in severity. As soon as things are starting to get comfortable and the benefits of the drug are starting to peek out, I've raised the dose and am back at square one (impatience). The study you posted above suggests the mechanism at work here -- initially NE and DA firing is suppressed, then it begins to recover. I am thinking that if you were to remain on a given dose for several consecutive days (like the recommended 5-7 days between dose increases), there would no longer be any noticeable side effects, at least in the range of doses we are discussing here.

2. The primary effects that I have noticed so far, particularly right before another dose when serum concentration is relatively low, or after I have somewhat adapted to a given dose and before increasing it, include enhanced motivation which has been most obviously apparent at work, increased libido (sometimes dramatically), and inconsistent effects on mood. My mood has often been better than normal and other times I've been irritable or crabby. I don't think it is fair to report on effects this early though, since it is like other antidepressants in that peak benefits are noted several weeks into therapy and my dose has been rapidly changing. I'm more interested, and you'll probably be as well, to see how I feel after I've settled in at 1.5mg for a week or two.

I'm not using any other psychoactive medications with the possible exception of memantine. I don't think that would affect the color of my pramipexole experience very much. It might guard against the development of compulsive behavior, but I never saw that as a serious concern anyway.

Edited by FunkOdyssey, 09 April 2009 - 09:27 PM.

[Logan]

Soooo... ultimately, pramipexole's mechanism is serotonergic (through the increased firing of 5-HT neurons)? Or is it also ultimately dopaminergic because dopamine firing recovers after 14 days AND the agonist is stimulating dopamine receptors?

Yes and yes. Both 5-HT and DA neurotransmission are enhanced as the study concludes.

I wonder if growth of new dopaminergic neurons might be a long term answer to depression, anhedonia, low libido, etc.

That seems to be a hopeful possibility.

1. How close are you to titration (a dose that you plan to sustain for months) or are you figuring that out as you go?
2. What are the primary effects that you attribute to pramipexole so far? Also, I remember you mentioning that you take memantine... are you on any other psychoactive drugs/supplements?
3. How bad are the sides? are you getting a lot of drowsiness? Drowsiness + motivation would be weird

1. I'm at 1.125mg now, this is only my second day at that dose. I started last Thursday with .125mg x3 daily and have been raising the dose every 2-3 days. This is not recommended -- you should wait 5-7 days before increasing the dose. I am probably going to go up one more time to 1.5mg. I was initially planning to settle in at either 1.125mg or 1.5mg, but the careful and time-consuming pill splitting required to take .375mg three times daily is getting old quickly.

I'm going to assert myself and answer your questions in a different order of my own choosing (dopamine agonism talking? lol)

3. The sides are annoying and are present with each dose increase. They include drowsiness, spaceyness / loopeyness, orthostatic hypotension, and a trend toward constipation. Each day I remain at the same dose, the side effects decline in severity. As soon as things are starting to get comfortable and the benefits of the drug are starting to peek out, I've raised the dose and am back at square one (impatience). The study you posted above suggests the mechanism at work here -- initially NE and DA firing is suppressed, then it begins to recover. I am thinking that if you were to remain on a given dose for several consecutive days (like the recommended 5-7 days between dose increases), there would no longer be any noticeable side effects, at least in the range of doses we are discussing here.

2. The primary effects that I have noticed so far, particularly right before another dose when serum concentration is relatively low, or after I have somewhat adapted to a given dose and before increasing it, include enhanced motivation which has been most obviously apparent at work, increased libido (sometimes dramatically), and inconsistent effects on mood. My mood has often been better than normal and other times I've been irritable or crabby. I don't think it is fair to report on effects this early though, since it is like other antidepressants in that peak benefits are noted several weeks into therapy and my dose has been rapidly changing. I'm more interested, and you'll probably be as well, to see how I feel after I've settled in at 1.5mg for a week or two.

I'm not using any other psychoactive medications with the possible exception of memantine. I don't think that would affect the color of my pramipexole experience very much. It might guard against the development of compulsive behavior, but I never saw that as a serious concern anyway.

I'm curious to know how things are going on the mirapex. I'm interested in this drug as well. I was on zoloft for years which is very much a serotonin and dopamine reuptake inhibitor. Unfortunately, I stopped taking after being on it for 7 years thinking that I was done with medication for good. Six months later a perferct storm of 4 or 5 circumstances came together, included the lack of protection I was getting from zoloft, and I had a major mixed episode. I think I opened my own little pandora's box.

Zoloft+Fish Oil+Working Out 5 days a week and I was feeling really good. Now, umm, not soooo much. All the injuries and surgeries are not helping. Currently I take 50mgs of Lamictal and 10mgs of Celexa. This is after being on about ten different meds in one year. I tried zoloft again and it wasn't quite the same. In hindsight I probably should have stayed on it, switching meds around in a fairly short period of time is not good for the noggin.

I just tried selepryl and it threw me off. It didn't overstimulate me really. After 2 drops it almost made me feel like curling up in a ball. I suddenly didn't really feel like talking. I tried 1 drop every other day and still felt off. This was just last week and I am feeling much better. I know that mao b is still inhibited. Maybe I would benefit from 1 drop every week or 2, but I think I am done with deprenyl for the time being, too risky. Anyway, I feel like my dopaminergic system, whether stratial or in the subsantia nigra or both, is completely F**ked. I used to have the hands of a surgeon, not anymore. Not feeling the stimulation or motivation either, much of that is circumstantial. My muscles aren't feeling so hot either. While I was on wellbutrin a few months ago I started to feel stronger physically in some ways, but it ended up giving me the shakes, way too stimulating. I definitely have to watch out for anything that is overstimulating(I won't touch coffee).

So, I am interested in trying mirapex. I have a doctor that is fairly open minded. Actually, there is a current trial underway investigating the efficacy of lexapro and mirapex together in major depression. I'm aware of the compulsive behavioral issues, people going out and developing gambling addictions, and subsequent lawsuits concerning mirapex. Seems kinda silly. I guess if the Pfizer didn't originally list issue as a possible side effect, maybe they deserve to get sued. I'm not worried about that, never been much of a gambler. Then again, I may become one after trying mirapex!

Back to the question after my little ramble...How is that mirapex workin out for you so far?

Edited by morganator, 21 April 2009 - 03:36 AM.

[StrangeAeons]

So, Mirapex is starting to come into serious consideration for me for psychiatric purposes. What's the availability? It doesn't seem to be proscribed very commonly for depression/anhedonia; psychiatry in America pretty much eschews dopamine agonists. So how are you guys getting it?

[tlm884]

Would Mirapex be a good alternative to an anticonvulsant for bipolar treatment?

[StrangeAeons]

I don't know the specific answer to that, and while yes there is some experimental evidence of it being effective in bipolar I would by no mean switch out the "mood stabilizer" component of your regimen. The anticonvulsants work more prominently against the manic aspect, and it would seems (though again, it's uncertain) that Mirapex seems to be more effective for the depressive aspect. Its tendencies to cause increases in pleasure seeking compulsions seems like a potentially dangerous synergy with a manic episode. Again, this is all intuition and further research may prove something entirely different about this paradigm; but it would be unnecessarily risky at this point with this little knowledge.

[notlupus]

Hmm, I wonder if I could talk the boyfriend into taking this...

[alexd]

Hmm, I wonder if I could talk the boyfriend into taking this...

Hi I am/have bi polar #2. Actually doing quite well with it for the first time in my life. Please look up my posts and you can get the whole regime. Just not going to rewrite it. The info might be useful. Good luck.

[notlupus]

Hmm, I wonder if I could talk the boyfriend into taking this...

Hi I am/have bi polar #2. Actually doing quite well with it for the first time in my life. Please look up my posts and you can get the whole regime. Just not going to rewrite it. The info might be useful. Good luck.

He's not bipolar, just lazy as hell. I suspect it's due to his crappy fast food diet and unwillingness to take even a multivitamin, but at this point I'd be happy with anything that made him want to get off his ass a little more.

[FunkOdyssey]

So, Mirapex is starting to come into serious consideration for me for psychiatric purposes. What's the availability?

Its available from the usual overseas sources, about $20-$30 for a month's supply depending on dose, made by Sun Pharmaceuticals.

[Logan]

I don't know the specific answer to that, and while yes there is some experimental evidence of it being effective in bipolar I would by no mean switch out the "mood stabilizer" component of your regimen. The anticonvulsants work more prominently against the manic aspect, and it would seems (though again, it's uncertain) that Mirapex seems to be more effective for the depressive aspect. Its tendencies to cause increases in pleasure seeking compulsions seems like a potentially dangerous synergy with a manic episode. Again, this is all intuition and further research may prove something entirely different about this paradigm; but it would be unnecessarily risky at this point with this little knowledge.

I agree, if you have ever experienced any type of mixed episode or are currently in an unstable bipolar state, I would consult your psychiatrist before trying this drug. If you are on a mood stabilizer or your moods are stable and are only experiencing depressive aspect of bipolar, you may benefit from Mirapex. I am almost positive that it does not function similar to anticonvulsants in influencing kindling in the brain that helps with mood stabilization. It would be nice if it did.

[Lufega]

this is starting to sound like something I'd like to try. I was afraid it was going to be another selegiline. A lot of hype but in effect, one big let down.

[Jacovis]

I think I hit a gold mine with pramipexole. It probably deserves it own thread. Its neuroprotective, neurotrophic, an antidepressant, anti-anhedonic, anxiolytic, improves motivation/initiative, boosts libido and reduces refractory time. It may be of specific value in Lyme as it prevents lipopolysaccharide-induced dopaminergic cell death. It may be useful as a general anti-aging drug, considering that an adult loses 5-10% of their dopaminergic neurons every decade and pramipexole may have the power to halt or reverse this loss.

Have any anecdotal reports surfaced of long term intake of this drug and 'permanent' improvements in functioning I wonder?
I like the idea of taking something which is working at preserving dopamine levels (and even increase them) long-term rather than neurostimulants (like dextroamphetamine and methylphenidate) which may decrease dopamine levels in the long-term.

[Lufega]

For someone like myself, who already has orthostatic hypotension, what do you think the long terms effects of this will be? I know at first it lowers NE and then levels "normalize". In my case, it should plummet, then elevate to a steady "low". Is there any literature saying if it will help normalize NE levels in the long run? I guess in my special situation, I should titrate this carefully, very, very carefully.

[StrangeAeons]

To avoid passing out while standing up, contract your abdominal muscles and hold your breath. I get a little orthostatic myself, and the spells tend to be worse when I'm more fatigued or depressed. For some reason this technique is really helpful, in spite of the fact that it seems to be a vagal maneuver and therefore aggravate hypotension; I think it works by increasing intracranial pressure, though, which prevents syncope by keeping the brain perfusion high.

[Lufega]

In light of what was discussed in this post.

Parkinson's and the 3 strike theory

If you are prone to PD or have some other type of dopamine related problem. Will using pramipexole and adding more dopamine to the system (one of the 3 factors leading to PD or more D-neuronal death) without using Isradipine or magnesium, lead to more neuronal death down the line? Or is neural protection an intrinsic factor or pramipexole?

[outsider]

He's not bipolar, just lazy as hell. I suspect it's due to his crappy fast food diet and unwillingness to take even a multivitamin, but at this point I'd be happy with anything that made him want to get off his ass a little more.

Fast food can be very detrimental on your health and energy level as I experienced myself. In took me 5 months of going to fast food everyday to start losing my health. I got it back in 1 or 2 months with detoxification.

[Gimzim]

This sounds really promising so far, and while I don't have anything to add I'd like to encourage those taking it to keep sharing their experiences. Somewhere down the line I might give this a go.

[StrangeAeons]

Well, I've gotten 2/5 IV infusions of Venofer, third one is today and I see my GI.
I'm aiming to see if the structural changes induced by pramipexole will in any way help ameliorate the purported dopamine receptor damage induced by chronic/early iron deficiency.
I'll make the case for it with the doc (RLS+elevated PRL, etc.), though since it's outside his discipline I might have to go through the process of getting another referral and appointment and so on *sigh*. Fingers crossed, I'll keep you guys updated on the stuff if I get it.
Unfortunately it may be somewhat confounding with the iron repletion. I'm debating whether to start it immediately if I get the script or to wait until a week or so after all the dose is infused. It's pure speculation, but I wonder if there would be a synergy between the iron repletion and the dopamine agonist.
EDIT: btw, haven't noticed any difference thus far from the iron, but I just got started on Monday.

Edited by PetaKiaRose, 08 May 2009 - 02:53 PM.

[StrangeAeons]

While I'm at it, I should throw in my two cents on the apparent MOA according to the study cited above about dopamine and serotonin firing:
it appears the pramipexole desensitizes autoreceptors; what this comes down to is throwing a wrench in the feedback mechanism that induces tolerance. If this is the chief effect of sustained dosage, than it doesn't so much induce structural changes that promote more growth but rather renders the brain less prone to tolerance (so essentially it is self-potentiating).
The serotonergic autoreceptor desensitization should mean that sustained pramipexole should have a powerful synergistic reaction with other antidepressants, particularly SSRI's; and one would be inclined to think it should reduce the (lengthy) time of onset for antidepressant activity. It probably wouldn't be safe to give with MAOI's without dosage adjustments.

[tlm884]

Does pramipexole have any memory impairment or cognitive slowing associated with it?

[StrangeAeons]

Got a six months' prescription for pramipexole yesterday (under the pretense of treating my restless leg syndrome). The doctor thought it was completely interchangeable with Requip (ropinirole).
The dose of the pill is 1mg, and I was instructed to take 0.5mg for ~1 week before going to 1mg (much less painstaking than FunkO's approach). I was also told to take it before bed.

Right now I'm debating taking it in the morning instead, but seeing as my main goal is in the long-term effects it doesn't really matter. Took my first dose last night, nothing spectacular to report. Will keep you guys updated.

[VespeneGas]

Got a six months' prescription for pramipexole yesterday (under the pretense of treating my restless leg syndrome). The doctor thought it was completely interchangeable with Requip (ropinirole).
The dose of the pill is 1mg, and I was instructed to take 0.5mg for ~1 week before going to 1mg (much less painstaking than FunkO's approach). I was also told to take it before bed.

Right now I'm debating taking it in the morning instead, but seeing as my main goal is in the long-term effects it doesn't really matter. Took my first dose last night, nothing spectacular to report. Will keep you guys updated.

Awesome! I was under the impression that divided doses were preferred for antidepressant/parkinsons purposes... or are you concerned about staving off restless leg syndrome?