Pramipexole (Mirapex) for anhedonia and negative symptoms?

I am currently on no medication as all were ineffective for what I suffer from. My cognition was never impaired luckily. I struggle with motivation and pleasure, to the point where I think about ending my existence everyday. If you can still experience pleasure from listening to music, watching movies, eating good food, and socializing with friends and have drive/motivation to accomplish trivial tasks like cleaning dishes, consider yourself lucky nonetheless…

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This drug might work on people that have no history of positive symptoms and/or are able to tolerate methylphenidate kind of drugs. For those who had it , taking Pramipexole would be risky in aggravating positives acting as a dopamine agonist of D2/D3. And I’m one of last group, though, nice find. (Might take the risk in the future, first going to trial Memantine and/or Memantine + Galantamine.)

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What puzzles me is that Rexulti (brexpiprazole) has significant affinity for the D3 receptor as well (Ki=1.14), higher than Abilify, and I was on it for 8 weeks at the highest recommended dose and did not feel any improvement of my negative symptoms…

My only hope is that Pramipexole’s affinity for D3 receptors, which is even higher than that of Rexulti, will make a difference. Also the fact that Prami is a full agonist rather than a partial agonist might be significant.

I’d try Vraylar, which has the highest D3 affinity of all, but it’s not available yet in Canada

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I’ve been suggested to take Brexi + Memantine as the most beneficial combo on both negatives and positives because of Brexi being the first SDAM - Serotonin Dopamine Activity Modulator, however I do not know why this might work better than taking it with a atypical. I’ve also didn’t research Brexi because it’s not (yet) approved in Europe and won’t be until somewhere in 2018/2019.

Anyway, maybe the affinity of Brexi at D3 is higher on a low dose, have you tried that? I’m also waiting for Vraylar, it’s approved in May this year in Europe but it’s still not on the Dutch market.

If you can tolerate methylphenidate and/or other dopamine agonists without aggravating positive symptoms I would say go on and trial Prami.

(I’ve obtained Memantine through a pharmacy in a foreign country but my dad, who got it for me, is being a dick about giving it to me because I’m a regular alcohol drinker :smiley: ass)

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And Prami or the results from the study is quite interesting, a change/improvement of 62% is a life-changing number!

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Here’s the table from the full article of Pramipexole adjunctive to Haloperidol showing differences in PANSS scores for the 15 patients included in the study… Looking at the Negative Subscale, the scores are interesting indeed. What bothers me though is that the PANSS negative subscale includes things such as Stereotyped Thinking, Lack of spontaneity and flow in conversation, Poor rapport, and Difficulty in abstract thinking which could all potentially be partly explained by positive symptoms or cognitive symptoms and may hardly have anything to do with motivational and hedonic deficits specifically. Patients could have improved in those aspects and it would already have dramatically reduced their PANNS-Neg. scores…They don’t break down individual negative symptoms improvement so it’s always difficult to conclude anything. But again, Prami has successfully been used in treatment resistant depression and parkinson’s with anhedonia so that is still encouraging. One thing to note also is that in the Haloperidol-Pramipexole study they’d increase Pramipexole dosages to as high as 10.25mg/day, whereas in the TR-Depression and Parkinson’s studies they’d only go as high as 5mg/day I believe.

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Here’s a link in which the individual PANSS subscales items are explained if anybody’s interested.
http://egret.psychol.cam.ac.uk/medicine/scales/PANSS

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I was on Wellbutrin which is a dopamine agonist (kind of, it also increases dopamine) but it did literally nothing for me except aggravate my positive symptoms

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This new drug is actually a 5HT1A agonist.

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@twinklestars

5-HT1A agonist drugs, as well as 5-ht2a antagonist drugs, increase dopamine in the prefrontal cortex, not in the reward center of the brain (which is also known as the mesolimbic dopamine pathway)… The original theory that negative symptoms originate from a mesocortical (prefrontal cortex) dopamine deficiency doesn’t hold true for those that suffer specifically from anhedonia. My belief is that they loosely counted people suffering from cognitive deficits (which are thought to stem from prefrontal cortex dysfunctions) as people suffering from negative symptoms (i.e. they put cognitive deficits and negative symptoms in the same basket) when they first came up with the mesocortical dopamine deficiency theory of negative symptoms… Take Abilify, Seroquel, Olanzapine, and I think pretty much all of the atypical antipsychotics for example, they are both 5-ht1a agonist and 5-ht2a antagonists and clearly they do nothing for the majority of people with anhedonia and negative symptoms unrelated to any sort of cognitive dysfunction…Although on paper, and for marketing purposes, it looks good to say that atypical antipsychotics correct the chemical imbalance (mesocortical dopamine deficiency) and therefore improve negative symptoms… When I first met my pdoc she told me right off the bat that they didn’t have any effective medication for negative symptoms and the solution was to do exercise and behavioural activation, yet if you look on the website of abilify and all atypical antipsychotics they will claim that they all work for negative symptoms (by increasing mesocortical dopamine)…

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For anyone interested in pramipexole, I contacted the famous psychiatrist in the US known to use it for treatment-resistant depressed and bipolar patients suffering predominantly from anhedonia. Here’s his answer, which is encouraging, , followed by my original email:

From Jan Fawcett ( jfawcett@salud.unm.edu)
​"Charles - Pramipexole is reasonably successful (nothing works all the time) look in my article for the response rates and duration of follow-up. I dose it all at night (as explained in my publication) I have followed patients up to 6 years without a relapse. Stimulants added to MAOI medications (Fawcett 1991) don’t seem as likely to develop tolerance, but it is difficult to get patients off of stimulants without a relapse. Re-read my paper and most of your questions will be answered. There are side effects in some cases. Jan Fawcett"

My original e-mail:
"Hi Dr. Fawcett, I suffer from anhedonia very badly and recently found out about pramipexole (I found your articles and youtube conference). However, I was wondering about two things:

  1. How successful does it seem to be? Meaning, does it help only SOME anhedonics, or nearly all? And if so, do the benefits seem to be long-lasting? (or do many patients eventually develop tolerance to pramipexole?)

  2. Do you recommend dosing it 3 times a day, or 1 time a day? (in some article you say one time, in others you say 3 times a day)

Lastly, I know you also prescribe stimulants to anhedonic patients but from what I’ve read there is definitely a risk of developing tolerance to the effects and therefore a need to constantly increase the dose to maintain the benefits. That said, I invite you to look at the scientific and anecdotal reports of people using nmda antagonists like memantine along their opiate and stimulant use to prevent tolerance. Thank you, Charles"

The article he is referring to is the first article of the two that I linked above in my original post. Here’s another article I found which he wrote which you can also look at (it’s the one that caused me to be unsure about the dosing schedule. In it, you see he starts by giving pramipexole T.I.D (thrice daily) and then later ends up giving it HS (at bedtime/once a day) Here’s the link for that article:
https://www.healio.com/psychiatry/journals/psycann/2016-8-46-8/{b63a041d-8eec-4b17-bae0-99b8d1f34913}/dextroamphetamine-and-pramipexole-combination-for-treatment-resistant-unipolar-depression

You can also have a look at the youtube webinar in which he describes in some detail successful cases he’s treated with pramipexole. Here’s the link for that one:
-https://www.youtube.com/watch?v=jHA-Gu0ZtMQ&t=2837s

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Did you already tried Prami? Or when are you planning in starting it? In the meantime I’ve tried Memantine, it back-fired on my symptoms, causing me to feel more depressed and psychotic. Right now I’m experimenting with Parnate (a MAOI), so far so good for my depression, for negative symptoms, it’s too soon to tell and the dosage is too low I’m guessing, I’m just on 20mg. My dad is in a foreign country where meds are less regulated and I was planning on ordering and trying Odansetron next for negative symptoms or should I go for Prami? I’m a bit reluctant with dopamine agonist though, so far the dopamine agonist have brought me no success (except Parnate on this low dose, even on this low dose I’ve been on for just 2 weeks I’ve noticed a slight decrease in positive symptoms).

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Just so everyone is clear pramipexole is not a stimulant. Dr. Fawcett just answered all of my questions in one single paragraph

Haven’t tried it yet…Currently trying effexor (no success with it). I’m going to ask to try prami next…I had read on Ondansetron but for some reason didn’t get a good impression from it. It’s a 5-ht3 antagonist. Mirtazapine is also a 5-ht3 antagonist, among other things, and I haven’t heard about many people suffering from negative symptoms having success with it… Maybe Ondansetron is a more powerful 5-ht3 antagonist than mirtazapine and therefore could be more useful? (haven’t looked into it)

There are a few studies that have shown Ondansetron to be beneficial for negative symptoms but in those studies they use scales like the PANSS which includes many things that I don’t agree should be considered as negative symptoms…and they don’t specify which negative symptoms it helped the most with

As far as parnate is concerned, and other maoi’s, most of what I’ve read (haven’t read much) is that for those that it helps with motivation and pleasure it tends to eventually fade and there’s a need to increase the dose…until it completely poops out at the max dose :confused:

Edit: Olanzapine/zyprexa is also a 5-ht3 antagonist apparently

You try Prami, I’ll try Ondansetron in the meantime, we’ll report to each other.

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I’m to start Pramipexole tonight. As yet another add on to my depression cocktail. @Szsurvivor thank you for all this information.

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please if you suffer from anhedonia, negative symptoms, or low motivation/avoition, reach out to me in private message, I think mirapex/pramipexole might not be the best option. I think I found more promising stuff!!! (this message is for everyone reading this)

@Skims @everhopeful and everyone

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Coming off the antipsychotic or gettin on an ap which has a shorter occupancy time might achieve the same thing as pramiprexole, possible without the possibility that symptoms will rebound or get worse. I think dopamine agonists may be a good idea especially at lower doses but then again i know nothing. Combining pramiprexole with an antipsychotic would negate the effects of the pramiprexole, especially with antipsychotics which bind very tightly at d2 and have a high d2 occupancy.

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Please share your experience with us when your on it! I’m interested in it as well but I’m also a bit reluctant to buy and try it because it is a dopamine agonist and may exacerbate positive symptoms.

Did you ever suffered from positive symptoms (hallucinations)?

Hi!!I have anhedonia for a long time and looking for solutions here.I wanted to private message you here but I’m new here and I have tried to look how to text you but I couldn’t.Please text me so I can talk to you about anhedonia and how to cure it.Thank you for your time.

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So tonight will be day 6. Its a long, slow 20 day titration from 0.5 - 2.0 mg. Maybe the first few days I had early morning awakening but that seems to have passed. Otherwise no SE yet.

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