thank you! yeah i started this channel some years ago because i realized there was a dire need for a doctor to explain meds to people in a way that is evidence-based but also in plain english. your comment is music to my ears. Going to start cranking out a video every week starting next month! please let me know if you have any meds you want me to talk about in future videos.
First off, THANK YOU for your desire and effort to serve this underserved community. Our son has severe, treatment-resistant depression and anhedonia. He recently went off his Prozak because he was sick of feeling 'nothing', but now needs a new approach. He hasn't had a psychiatrist in many years, after his last one's MO was a 3 minute interview followed by throwing drugs at him based on drug company kickbacks (I'm not being facetious, he was actually convicted of that). Finding a psychiatrist who is taking patients is hard enough. HOW do we find one who has a specialty or desire to work on anhedonia cases instead of just the 'run of the mill' practitioner? The psychiatrist search engines do not include a place for specialties or keywords.
im so sorry to hear about your son. I can only speak from my own lived experience, but I haven't met any psychiatrists that specifically try to treat anhedonia. They all just assume It will get better if you treat it like just one more clinical depression symptom. Sad truth is that commonly prescribed antidepressants often worsen anhedonia. Prozac, as a potent SSRI, will very often flatten mood and cause the "nothingness" you are describing. I have found adding pramipexole to an SSRI, or just prescribing it as monotherapy, can alleviate anhedonia. It can be hard to find any doctor, PCP or psychiatrist even, that will do this though. For severe, treatment-resistant depression, I'll often refer them for ketamine, esketamine, or TMS. I've seen miracles with all three of those, and they work QUICKLY when they do work. I hope to come out with an ebook that includes all potential options for anhedonia; things people can try and also medications and treatments they can talk to their doctor about.
@@OllertonMD Thank you for your reply Doctor. We appreciate your thorough response. Our son has tried Ketamine (injected) and is currently doing esketamine. The injections had a more profound positive effect than the esketamine is having, but it didn't last and was too expensive to continue since insurance won't cover it. He will likely try TMS next, though we are again having trouble finding doctors to support him in our area. Thank you.
You need a neuroscientist/pharmacologuist to help you. Fluvoxamine is like Prozac but less emotion blunting. Wellbutrin also does the same thing but also increases adrenaline more.
I have anhedonia after a bad reaction to fluoxetine. I had akathisia and was awake for 10 days straight because of the restlessness, terror and pacing. I also had jerking limbs, non stop diarrhea and other symptoms. Ever since this reaction I am left with severe anhedonia and sexual dysfunction. I can’t feel music, and all my hobbies and things like socializing, movies, video games, reading, sports, sex, eating etc are all completely flat. I also lost all motivation since nothing feels good or rewarding anymore I feel hopeless and don’t know what to do or what to try. I just want to be able to feel pleasure again and have motivation to live a happy life again. I’m not sure why I had this reaction since I was on high dose fluoxetine in the past for OCD and it was helpful with minimal side effects. It’s been 2 years since then but I’m not any better. Part of me is terrified of trying medication again but I feel like things won’t get better on their own at this point either. I’ve looked into things like Wellbutrin, MAOI’s, pramipexole, low dose Abilify, lyrica etc but haven’t tried any out of fear and low motivation.
I am so sorry man that sounds absolutely horrifying. I hope you have or can find a good psychiatrist who can guide you through different options. Hold in there my friend. There is always hope.
@@user-sf3qr6jt9j yes I did but mine was from finasteride propecia and have had anhedonia for 24 years and still ongoing. Have tried pramipexole and it didn't cure me, it helped a bit with motivation but it also has a down side it down regulates your dopamine receptors so once you stop using it it's even more difficult to feel pleasure
@@OptimizingSpirit Hello, I have severe anhedonia after taking benzos I stopped them all and take vitamin and omega 3 can you help me with some food or supplement that helps me improve please help me 🙏
thank you a lot doctor, i'm from iraq, I suffered from anhedonia 6 years ago, when I started taking fluvoxamine for OCD. After ten days of taking it, the OCD went away, but also all my personal feelings and pleasure went with it, and I immediately developed peripheral neuropathy, and it was confirmed by a neurologist and an EMG. I'd rather have OCD than this hell. Anhedonia varies in severity depending on behavioral activation, but it remains a bad thing. You have given me great hope that there are medications that can help. Thank you again.
I have a question, doctor. It has been shown that I have a significant deficiency in vitamin D3 and folate, as well as a significant deficiency in testosterone. “I am male.” Can these things cause anhedonia? Also, can nerve inflammation lead to anhedonia? What do you recommend to treat inflammation?
in my experience vitamin D can cause anhedonia (patients describe it as lethargy, no motivation) and low testosterone can definitely cause a loss of positive emotions. Not sure on the folate one, folate deficiency is pretty rare in my country given it is added to flour. Theoretically it might though; folate is essential to create methylfolate which is needed for adequate neurotransmitter production, including dopamine.
I have prescribed pramipexole to patients with BP 2 repeatedly, usually with good effect. good luck my friend! the risk of switching to hypomania on pramipexole appears fairly low
Those Compulsive behaviours are the exact same as bipolar mania !!!!.. which is great, till you get to the uncontrollable rage stage and become violent
luckily, pramipexole has successfully treated bipolar depression in many instances with a low rate of switching to mania. But if someone is bipolar and on pramipexole they should be on "oppositional therapy" to prevent mania anyways, ie lithium, an anticonvulsant or a 2nd gen antipsychotic. thanks for the comment!
After 6 years of chronic depression and Venlafaxine, I developed severe anhedonia which progressed into a negative/cognitive schizophrenia-like state. I suspect the venlafaxine nuked my dopamine but I cannot drop it because of depression. Would taking Pramipexole and slightly lowering Venlafaxine make sense? I don't have any history of psychosis or OCD.
Great video as usual. As someone who is suffering from this since years I have a few questions: 1. Do you (generally speaking) recommend trying MAOis before Pramipexole? 2. Do you think a similar effect can be reached by long-term practice of mindfulness exercises? 3. The only short term relief I get is from caffeine, especially after I've withdrawn from it for a few days and then start drinking coffee again. Thoughts on that? 4. Some people recommend ketogenic diet, would you recommend it?
1. I would usually not try an MAOI before pramipexole in any of my patients 2. Mindfulness reduces anxiety and might increase tonic dopamine, so this is a reasonable option for many people to try, especially since chronic unpredictable stress is a major cause of anhedonia 3. Probably due to dopamine increase, and it helping after a break is likely from dopamine receptors upregulating during cessation 4. at this time I don't recommend keto diet to my patients given the lack of evidence it improves mood, and VLC diets have been shown to worsen mood and anxiety in many people, although most of these studies weren't specifically about being in ketosis as far as I understand. A plant-focused or mediterranean diet has much better evidence of being able to improve mood, such as with the SMILES tiral hope this answers your questions!
@@Zigoliokas MAOIs are very rarely used anymore given its extremely narrow therapeutic index (ie the dose needed to help is uncomfortably close to the dose needed to harm, or kill). A 2 week supply taken all at one, if someone were suicidal for example, is enough to kill someone sometimes. Also, unless you are going with low dose Ensam, MAOIs require a very strict diet to avoid the "tyramine cheese effect" or hypertensive crisis. MAOIs also often cause pretty significant dizziness and low blood pressure. Also, you can absolutely not be on any meds or supplements that increase serotonin syndrome, so a patient would have to be completely off antidepressants for 2 weeks before an MAOI is considered. So overall, MAOIs are much more difficult to prescribe and take compared to pramipexole. I am not against MAOIs at all though btw. I am very open to prescribing them in the right patient. It would have to be a patient that has not had SI in years and has never had a suicide attempt, esp via overdose attempt. And the patient would have to be high-functioning and motivated enough to follow a very strict low-tyramine diet, and not be on any other serotonergic med. So I just don't have many patients that would qualify. But if I find the right patient, I Would be excited to consider one. I am really the only psychiatrist I know in real life that ever even really considers them an option. Most psychiatrists would refer to ECT before trying an MAOI, which seems over the top to me in many cases.
DR, reading around I was struck by a few results that showed diminishing returns from pramipexole for another atypical (but likewise arguably very reasonable in theory) use, as adjunct to methylphenidate for ADHD. The papers in question showed significant improvement relative to standard methylphenidate treatment on all scales -- until six weeks of the study. At the 8, 10, and 12 week marks these results curved back down to insignificance and eventually began to throw up some insignificant, but potentially suspicion-raising results of impairment relative to methylphenidate alone. Central dopamine homeostasis seems to be a fickle beast! This is all to say -- can I ask if you have encountered, in your anhedonia patients, an insensitivity to the therapeutic effects against anhedonia that develops after a time? If so, was there a strategy in response? Or have you on the contrary not seen any problems of insensitivity developing to these antidepressant effects in your pramipexole patients over time? Thanks so much for your informative video!!
very interesting question. The longest one of my patients has been on pramipexole that I prescribed specifically for anhedonia has been a little under a year, so keep that in mind- but none of them have built a tolerance to its anti-anhedonic effects yet. it could be that any focus-enhacing effects from dopamine agonists wear off over months though, like the studies you cite suggest. Although I think risk of tolerance is going to be dramatically higher mixing a stimulant with a dopamine agonist than either one alone- mixing an amphetamine or methylphenidate drug with a dopamine agonist is a very intense combo
Hey I was looking for a answer to my DP DR disorder with many more to and but anyways my doc started me on adderall and the first time I took it my brain went to feeling like I did 30 years ago when I felt real and haven’t felt normal and n hell every day since,but was just probably about 30 minutes my mind was clear remembering everything and was in tears because it’s been so long sine I was a real person…I know you probably don’t understand my writing but I wish there was a way to contact you or do some trial’s on my crazy mind and views…idk idk just saying there might be a link to that medication and the ones I’m on
I've had anhedonia for 15 years or so. It doesn't let up, I enjoy nothing except sleep. Ive tried many many depression meds several times over. They don't work. Are you able to write a script for someone on the internet, or can you give me a referral for it? Please, this has taken a majority of my life away from me, and the thought of living another 30 or 40 years with this is terrifying!
Hi, I live in Germany and all the doctors that work on(get paid from) public health insurance don’t prescribe pramipexol to depressive patients. But I went to a "private" neulologist(he is even a professor) where I paid 180 euro for an appointment. The doctor listend to me and was reviewing /googling “ pramipexol & anhedonic depression” in the web. He gave me a privat prescription , with that I could buy it in the pharmacy. Normal doctors stick to national guidelines because of security issues, they can be somehow sued when a patient get worse or whatever, and lost their right to get paid from public health insurance. This is what I found out for Germany. In another youtube viedeo someone sad that you can by pramipexol in mexico without prescription. I don’t think that its good to take medication without a doc. But maybe you find a doc who accompanies you. Where are you from? Good luck for you!
Hello, very interesting video, especially on how the role of dopamine is neglected in large parts of psychiatry even though many symptoms of severe/melancholic depression stems from dopamine dysfunction (eg. anhedonia, cognitive impairment, psychomotor retardation etc). It's also interesting to note how medicines for Parkinsons (not just Pramipexole but also selegeline etc) also have utility in treating depression. Vice versa with the antidepressant tranylcypromine having good effects for Parkinsons (both selegeline and tranylcypromine are in a similar class of medications). Talking about tranylcypromine and selegeline, I wonder what you think of Monoamine oxidase inhibitors (MAOIs). They are (I think) one of the few antidepressants that as an entire class robustly boosts dopamine due to their mechanism of action (inhibiting monoamine oxidase which in turn boosts dopamine, serotonin, norepinephrine etc). I have heard a lot of anecdotal evidence on those using tranylcypromine saying that it has helped enormously with their anhedonia, which makes sense due to its robust dopamine boosting effects. There is a lot of reluctance out there regarding its use (eg. tyramine pressor effects, drug/drug interactions etc), but I also sense a kind of renaissance in interest of these drugs, largely spearheaded by Dr Ken Gillman and his website/publications on them. Probably that renaissance in interest also comes from people trying all the "newer" antidepressants that are largely serotonergic (eg. SSRI/SNRI) but still not getting adequate relief from their illness, and so they turn to MAOIs for remission. Anyway I am interested if you have any thoughts/ideas etc on MAOIs, thanks a bunch again for a very interesting video.
wow that was such an awesome, thorough and thoughtful comment about dopamine and MAOIs. I pretty much agree with everything you have said. I a actually emailed Dr Gillman in late 2019 or early 2020, and we were going to have a skype call to discuss MAOIs (I was early in residency training and didn't have any luck finding an attending/supervising psychiatrist that was interested in prescribing them), but then COVID happened and I was at "gound zero" (was training in Seattle) and it never happened. I would really love to have him on the channel to discuss MAOIS, I love his quirky but awesome, thorough website. Your comment has inspired me to think about contacting him again to see if he would be willing to accept an interview on my channel. He is such a rare gem, one of the only doctors that I know of that promote and educate the masses about MAOIs that I am aware of. I have always been interested in MAOIs, I think they often work when nothing else has (according the studies I've seen on treatment-resistant and melancholic depression). And agree that meds that are more heavy on MAOI-B inhibition might be an very good option for some people's anhedonic depression symptoms. I've seriously considered trying an MAOI now that I am out of training (since last summer) but its hard to find a patient that it is appropriate for, at least for the patient demographic I serve in a rural area. Finding a patient that is willing to follow the strict diet, and finding a patient that is also willing to get off their SSRI/SNRI completely before starting it, AND finding a patient that is at low risk of an overdose attempt has been hard so far. Thanks again for the great comment. I do want to come out with a slew of videos exploring MAOIs.
Hello, I also agree that in my personal experience dopamine is highly neclected in psychatry. Most of the doctors or therapists I ´ve seen didnt seem to understand or know the symptom anhedonia. I´ve been given Tranylcypromin in hospital last year. I also listend to the videos of Dr Gillman and apreciated them a lot. Unfortunately I couldnt get to the therapeutic dose of 20mg, because from 15 mg onwards I became very sleepy and weak. But i know people who did good on tranylcipromin. I might try Nardil later. Now I´m giving Pramipexol a chance to work. thanks for your informative comment!
@@OllertonMD After years of trying various antidepressants, it was finally methylphenidate that helped practically straight away. It was clear to me 20 years ago that dopamine plays a huge role but is simply ignored.
@@paradoxeintervention5390 its crazy to me. Psychiatry has known for 70+ years that dopamine is vital to mental health, and yet doctors put patients on an endless merry-go-round of serotinergic antidepressants for patients that clearly have a dopamine signalling deficiency (low dopamine causes more melancholic/neurovegetative symptoms like fatigue, apathy, anhedonia, dread with daily activities, emotional numbness). The problem is, is that if dopamine is an issue for a patient, boosting serotonin will WORSEN low dopamine signaling. It also bothers me that a majority of antidepressants don't substantially increase dopamine. Wellbutrin is the only commonly prescribed antidepressant that boost dopamine, but even that is questionable (rodent studies show it boost dopamine; in human trials, its dopamine effect seems not as substantial or clear). There is Emsam and nardil, but those can rarely be prescribed for various reasons. Thats why I am so happy to have stumbled upon pramipexole. Its not a controlled substance and potently increases dopamine signaling (doesn't actually increase dopamine, but sidesteps low dopamine by directly agonizing its receptors). Hoping new antidepressants that target dopamine get released, but I'm not holding my breath.
@@OllertonMD what I also don't understand is how some psychiatrists prescribe antipsychotics (outside out of low dose aripiprazole and other smal exceptions etc) to treat depression, as their raison d'être is to decrease dopamine!
Thank you for giving so much attention to this topic and providing such interesting info. Where are you licensed to provide services/medication management? You seem genuinely interested in your profession.
thank you my friend! I am only currently licensed in the state of Montana, but I hope to add Wyoming soon too. And yes I genuinely love psychiatry because I love seeing people start loving their lives again when their mental health improves through meds, therapy and lifestlye change. Its the best feeling ever.
Hi Doctor, thanks for all the great info, this info gives hope to many who thought that they have exhausted all of their options. What are your thoughts on adding pramipexole to bupropion? Would this allow you to take lower doses of each due to synergy, or contraindicated? Thanks for your time!
ive mixed both of those multiple times with good success, although once patients are on pramipexole they usually dont even need to be on bupropion at all anymore
I have a question that is bugging me. I do have anhedonia, also CPTSD, I've had anhedonia for 15 years, nothing tackles it. But I honestly feel, I have no idea if it's possible that my anhedonia has to do with serotonin. Is that even a thing? I have a strong drive to do stuff, I'm very active and motivated even though I'm mostly in a freeze state, it will not stop me from cleaning which I used to love. But now I still do it and I expect to be happy but then comes disappointment. No pleasure, just a chore... I'm doing EMDR and my therapist says I need more time but cmon, I seriously cannot live like that. It's horrid. I did go through about 50 meds, they did nothing except I felt like I did meth after most of them but my mood didn't improve. So I'm off meds for almost 2 years now, I feel much better off them than on them, I'm learning to regulate my emotions but I feel like feeling positive emotions after doing things I like (I do more: yoga, dance, walks in nature, caring for animals, spending time with my long time partner) would really help me get it all together. I have it all, besides a job and a degree but I will do that when I'm able. I think if I felt pleasure my life would be great... I don't remember how it is to feel nice, it's been so long and I was a child, all a blur honest... So... can it be a serotonin issue?
I'm sorry you struggle with trauma :(. Anhedonia isn't thought to be from a lack or serotonin, and increasing serotonin has the potential in many patients to worsen emotional numbness. Dopamine is thought to be a big player in anhedonia. Trauma and chronic stress/fight or flight is an extremely common cause of anhedonia, and for many traumatized patients, anhedonia will 1. not improve until their trauma and PTSD is thoroughly processed in therapy and 2. is often the very last symptom to go away. IE it can take months after PTSD is substantially healed for anhedonia to go away. Good luck my friend.
@@OllertonMD thank you for your response. So that it gonna take a while cause I've been doing EMDR for over a year and we're not even halfway there :-(
@@leniwiec2401 keep in mind I of course can't guarantee anything and I am not your doctor. If someone's anhedonia is caused by trauma, and trauma is resolved, there is a very good chance the anhedonia will improve substantially over months. Someone with trauma could also have other causes of anhedonia that are unrelated though, like sleep apnea, brain inflammation, low vitamin D, fried D2 receptors from chronic drug or cannabis use, etc. I do hope your emotions spring back to life after your trauma journey ends though.
Also combo bupropion + low dose amisulpride give also instant relief. Amisulpride is an antipsychotic at normal dose (200-800mg/day) but conversely is dopaminergic at low dose (25-50mg) and the effect is immediate 😊
YES! Thank you for bringing awareness to amisulpride. I never was taught about it in my 8 years of medical training, but ive read the research on it and am considering prescribing it to some of my patients.
@@OllertonMD Unfortunately doctors seems to be programmed by factory to treat depression increasing only serotonin through SSRIs......I realized that there was some link with dopamine instead of serotonin when I tried for the first time amisulpride(I took Deniban 50mg per day). First line SSRIs, SNRI (venlafaxine) and NaSSA (mirtazapine) does not work at all for me. Mirtazapine was basically a sleeping pill while SSRI a chemical castration. Amisulpride gave me some motivation to do things and get out of the bed but does not improve my cognitive impairment and brain fog. I was switched to bupropion that at the start was a miracle drug! I was finally able to do things that had become a struggle for me before, i enjoyed hobbies again and was able to focus and multitask without feeling overwhelmed. I thought I was definitely out of that dark cloud that was above me for over 2 years and finally see the sunlight when unfortunately the effect started to fade out. Then doubled the dose and it seem to work but it's still not as effective as it was in the beginning. Now I'm on bupropion but sometimes when I felt anhedonic I take a 50mg amisulpride pill (it's an instant happiness pill) and it works in hours but i'm terrified that combo might suddenly stop working at all 😪.
@@OllertonMD Here all doctors seems to be programmed by factory to treat depression increasing only serotonin through SSRIs......I realized that there was some link with dopamine instead of serotonin when I tried for the first time Deniban 50mg (amisulpride) added as augmenting drug after the first line SSRIs, SNRI (venlafaxine) and NaSSA (mirtazapine) does not work at all for me. Mirtazapine was basically a sleeping pill while SSRIs a chemical castration. Amisulpride gave me some motivation to do things and get out of the bed but does not improve my cognitive impairment and brain fog. Furthermore the cronic use it's known to skyrocket prolactine that is not good for a young man...so I was switched to bupropion that at the start was a miracle drug! I was finally able to do things that had become a struggle for me before, i enjoyed hobbies again and was able to focus and multitask without feeling overwhelmed. I thought I was definitely out of that dark cloud that was above me for over 2 years and finally see the sunlight when unfortunately the effect started to fade out. Now doubled the dose and it seem to work but it's still not as effective as it was in the beginning. Now I'm on bupropion but when sometimes I feel anhedonic and letargic I take 50mg amisulpride which wipe out all that bad thoughts within hours....it works but i'm terrified that this combo might suddenly stop working at all 😪
@@OllertonMDHere all psychiatrists seems to be programmed by factory to treat depression increasing only serotonin through SSRIs....but I realized that there was some link on dopamine instead of serotonin when I tried for the first time Deniban (amisulpride 50mg) that was added as augmentation strategy because first line SSRIs, SNRI (venlafaxine) and NaSSA (mirtazapine) does not work at all for me. Mirtazapine was basically a sleeping pill while SSRIs a chemical castration drug. Amisulpride gave me some motivation to get out of the bed and do random things (like cleaning house) but does not improve my cognitive impairment and brain fog. Furthermore the cronic use is known to skyrocket prolactin that it's not good in a young man....so I was switched to bupropion that at the start was a miracle drug! I was finally able to do things that had become a struggle for me, enjoyed hobbies again and was able to focus and multitask without feeling overwhelmed when unfortunately the effect started to fade out. Now doubled the dose and it seems to work but it's still not effective as it was at the beginning and occasionaly I feel anhedonic and unmotivated. In that occasion I take my magic Deniban pill that wipes out within half an hour all that bad. It works but I'm terrified that this combo bupropion 300mg + amisulpride 50mg might suddenly stop working at all 😢
@@OllertonMD Here all psychiatrists seems to be programmed by factory to treat depression increasing serotonin through SSRIs....but I realized that there was some link on dopamine instead of serotonin when I tried for the first time Deniban (amisulpride 50mg) that was added as augmentation strategy because first line SSRIs, SNRI (venlafaxine) and NaSSA (mirtazapine) does not work at all for me. Mirtazapine was basically a sleeping pill while SSRIs a chemical castration drug. Amisulpride gave me some motivation to get out of the bed and do things but does not improve my cognitive impairment and brain fog. Furthermore the cronic use is known to skyrocket prolactin that it's not good in a young man....so I was switched to bupropion that at the start was a miracle drug! I was finally able to do things that had become a struggle for me, enjoyed hobbies again and was able to focus and multitask without feeling overwhelmed when unfortunately the effect faded out. Now doubled the dose and it seems to work but it's still not effective as it was at the beginning and occasionaly I feel anhedonic and letargic. In that occasion I take a 50mg amisulpride pill that wipes out within half an hour all that bad thoughts. It works but I'm terrified that this combo might suddenly stop working at all 😢
There are just a few tiny studies that ask this question but so far it looks promising. I would be very, very surprised if levodopa did not improve anhedonia. It has been shown to reverse anhedonia in primates so far. Since L-dopa straight up becomes dopamine in the brain (would be more effective if combined with carbidopa), and low dopamine is a key to anhedonia, it would be very puzzling if it didn't work. I've never tried levodopa or carbidopa/levodopa. in my patients with anhedonia, but its something I've considered. Most of my anhedonic patients respond to pramipexole so I haven't really had to go there yet.
I've tried Proza, Paxil, Lexapro, Zoloft, Abilify, Lamictal, as well as Wellbutrin and the XR form. Would I be able to possibly bring this up to my psych since the typical SSRIs just haven't been working for me? I usually just get ED and eat a lot on top of anhedonia.
When a doctor isn’t personally familiar with more obscure treatment options, it can help to show them that there is enough evidence from decent quality human trials for it to be a rational option to try even if it’s not the standard of care and even though it doesn’t have the same level of evidence of standard antidepressants. Here is a meta analysis you might want to print off and bring in to your appointments and it might increase the odds of them being willing to try it if you say something like “I understand this isn’t a common thing doctors to prescribe but my anhedonia hasn’t improved in any other meds and I am interested in trying something outside the box.” It might also increase your odds if you review the side effects and discuss them in the appointment them and explain that you understand the risks and side effects and are still willing to try. Ultimately there’s no way to know if any given doctor is going to be willing to try pramipexole for depression or anhedonia though, but I wish you the best of luck. Here is a good study to look over and maybe even bring to your next appointment with your doctor: onlinelibrary.wiley.com/doi/10.1111/acps.13055 If they seem hesitant you can also say “can you look into it and let me know later if it’s something you are willing to try for me?” Since most doctors (rightly so) will not feel great about prescribing a medication off label without being acquainted with the evidence, risks and benefits
Wow, I think most EVERYONE wishes YOU could be their Doctor! Ever think about internet subscriptions Doctor? Would be great. SOO many millions are suffering so bad with this. Very interesting and Thanks so much for discussing this extremely important subject.
thank you so much for the kind words. My dream has always been and continues to be to set up a virtual telepsych clinic and get a medical lisence in 30+ states so I can focus on helping people with anhedonia and treatment-resistant depression. I have a full-time job at a hospital right now but in the next 2-5 years that is the plan!
Hello, doc. I'm from Brazil, thanks for the awesome video and sorry for bad english. I was wondering if you could explain this phenomenon to me. I have had anhedonia for years and recently my psych tried pramipexole with me and we observed the following: Low doses (0.5-0.75mg) improve my sexual dysfunction, but when increasing the dose (2mg), the anhedonia worsens considerably. Why do you think this happens? Have you ever observed this reverse effect in any patient?
Fala Mauricio. Nao sou o medico do vídeo mas tenho estudado bastante a respeito para tentar superar a minha anedonia. O remedio que voce citou eh um agonista da dopamina. Ou seja, ele aumenta a dopamina circulante ali no cerebro. Acontece que quando voce aumenta a dopamina de forma exógena (que vem de fora) de forma relevante, o cerebro tenta ``equilbirar`` esse aumento subito aumentando a funcao das enzimas monoamina oxidase A e B, que vem e ``limpam o excesso`` de dopamina e outros neurotransmissores circulantes no cerebro. Agonistas de dopamina (remedios pra deficit de atencao, parkinson etc) funcionam apenas em doses baixas para aliviar a anhedonia, quando nao ativam as enzimas MAO e nao fazem downregulation de receptores. Como agonistas da dopamina fizeram isso contigo, tudo indica que algum remedio INIBIDOR das enzimas MAO possam resolver a sua anhedonia. Converse com seu medico a respeito de MAO-INHIBITORS
I had recently been on 4mg pramipexole and the side effects were too much for me. The doctor change me over to the 4.5mg Extended Release and all of my issues with the side effects went away almost immediately. The ER is much smoother it its release.
Very interesting! I've only done IR so far. Will consider ER more often. I tried once, but Medicaid refused it. I think I'll have better luck with trying to prescribe ER with patients that have commercial insurance. Medicaid will do anything to save a penny here or there.
@@OllertonMD I have commercial and they paid. The price difference is ridiculous. I think 30-days of IR is about $20 and the ER is $1,000. I tried breaking the IR into 4 doses, but I still ended up with 4 spikes. With ER, it is like "did I remember to take it? " because it is that smooth.
I have been on the drug about 8 months now. I am now on 4.5mg of Extended Release and that has made a big difference in lowering the side effects of pramipexole. I would say that I am about 25-33% better since starting prami. I haven't felt any real improvements in many weeks now, however, I also have not had any downturns or relapses. It seems that I have entered a maintenance phase and I am not sure that I will see any more positive surges. it was at the 3-4mg doses before I noticed any positive changes, smaller doses had little to no effect for me.
@@scottvk4129 I also experienced fewer side effects (mostly less sleepiness and less intense sleep attacks) after switching to extended release. Do you just take it once a day?
thats an interesting question. All of the studies I've seen has used instant release as far as I know. I've always used instant release with good effect with my patients. ER could be a possibility to mitigate side effects though, like if someone has nausea on it or something
Have you ever looked at what Chris Palmer a doctor in Boston is talking about a low carb or ketogenic diet to restore energy homeostasis in long covid. Bipolar and schizophrenia on occasion. Wonder if you have ever considered using taVNS in your patients with anhedonia or Avolition issues. Parnate as well, maybe in combination with a low carb lifestyle. There certainly are desperately needed drugs for anhedonia conditions which are rare but devastating, also looking at the work of Dr. Diego Pizzagalli at Mcclean studying it in relation to the CMS model
How tf did you know about the white noise music thing? That is, in fact, a Thing? I went all around my house trying to find the faint 'radio' that was always playing in the next room, playing fake yet familiar music until I turned off all the air purifiers. What in the sweet Psychosis is that?
its my job to know about weird and unusual side effects :) it is indeed a thing. when psychotic symptoms are very mild, it tends to be more about your brain misinterpreting real sounds than sounds entirely made up by your brain, which happens when psychosis becomes more severe
I have Schizoaffective disorder and I’m currently on 40mg of Latuda. I used to hear voices of neighbors or other people talking poorly about me. I also have compulsive behavior like drug abuse I’m 45 days clean from Nicotine, Kratom and Xanax (tapered with Valium). Everyday has been a struggled. My Prozac no longer works and my libido is ruined permanently I currently have severe anhedonia and nothing works. I have constant urges to drink and do drugs and I risk relapse everyday. Would Pramipexole work for me or should I try something else? I literally can’t enjoy anything in life and I feel dead inside Edit- I also was prescribed 5mg of Abilify and I got severe akathisia
did the anhedonia start after you started tapering off, or stopped, nicotine, benzos and kratom? all of these can and usually will have anhedonia as a post acute withdrawal symptom, which can last for months
@@OllertonMD My doctor told me it was likely protracted withdrawal from Kratom. I was taking heavy amounts of extracts and had to quit CT because of tremors and psychosis. The withdrawals were very severe and I didn’t sleep for a week. I still crave Kratom to this day After 30 days, my sleep went back to normal; but on day 42, I relapsed and had another Kratom extract. My sleep has been shit again for the last few nights; however, I didn’t feel other physical withdrawals unlike the first time I quit My doctor recommended that he rises the Latuda dose
What's your take on suggesting this medication for someone trying to recover from long-term stimulant use and facing immediate anhedonia post-cessation? Typically, SSRIs are recommended, but they've proven ineffective in the past.
I would personally never prescribe an SSRI to someone that is suffering from stimulant PAWS anhedonia, given boosting serotonin will reduce dopamine long-term. I would venture to guess pramipexole would be effective for anhedonia from chronic stimulant use.
I took thioxanthene last year due to a wrong treatment, and since then, I have been suffering from Anhedonia. In this situation, can I take Pramipexole to activate my dopamine receptors?
Tramadol worked miraculously for my anhedonia for about a year, but the late term side effects were too much to bear..Now I'm 4 months off and the anhedonia is worst then ever, like it just destroyed my dopamine receptors permanently..very discouraged.
@@michaelsteven1090 the only drug I know of that has been shown to permanently destroy dopamine centers in the brain is cocaine and meth. you might recover if you stay off of things that hammer dopamine receptors for long enough. Keep in mind that poor sleep, depression, and PTSD are main causes of anhedonia as well, and if someone hasn't addressed those, there is a good chance anhedonia will continue
@@OllertonMD Thanks doc..at 64, I've unfortunately learned that all the good, working receptors I had are gone..Maybe from "above avg" abuse and age..I think its the combo..Nothing prescribed or even recreational helps like it did, just for some relief..Am I right about aging receptors not working like they use to?
@@michaelsteven1090 i cant really comment on your specific situation since you aren't my patient, but in general, it can take months, maybe years of abstinence from hard drugs or cannabis, for dopamine receptors to get back to some sort of baseline. People's anhedonia usually improves substantially after *protracted* abstinence. The only drug I know of that appear to potentially permanently damage dopamine signaling is cocaine and methamphetamine.
thank you for your video, very informative is it possible to consult you in PM I am going through severe anhedonia, before going on a possible treatment
first off, pramipexole can cause sedation, which is why it is usually prescribed at night, but even then, some patients have next day sedation. for some people, it just wont be tolerable/won't be a good fit for their brain/body. Secondly, if I am trying to treat anhedonia, 0.375 is way too low. I start people at 0.5 mg and increase by 0.5 mg every 2-4 weeks until we get to 2-3 mg nightly. The studies that use pramipexole for treatment resistant depression use dosages of 2 mg, one study used all the way up to 5 mg! I've never ventured that high though. The highest I've needed to go is 3 mg.
@@OllertonMDthank you for your elaborate response. I once tried a double dose of 0.375 and I felt very out of place, agitated etc. maybe this drug is not suitable for me. Also caffeine, amphetamines, modafinil and other stimulants make me sleepy or tired. Pramipexol was my last resort to resolve anhedonia.
a patient that has compulsions on pramipexole can do common-sense things like change their environment and habits, but if the compulsions are serious or potentially will cause catastrophic outcomes (like a recovered gambling addict that starts getting urges to gamble again and could destroy his or her life savings) then it is usually discontinued
Hello Dr. Hope you're well. Do you have any recommendations I may speak to my own personal psych. about regarding anhedonia and cognitive dysfunction? I am literally learning disabled now as compared to my previous self. Not tooting my own horn believe me but I was an outstanding engineering student now my cognitive state is so terrible I simply cannot remember things that happened mere minutes ago. Do you have an recommendations regarding medications for anhedonia and severe cognitive dysfunction I may bring up with my psych? Thank you. Greetings from Canada.
from my experience of being prescribed pramipexole for restless legs syndrome, is after a couple years, you will likely develop a movement disorder. But in the meantime, you likely will feel "happy", for about a year. Then when you get off, you're worse than when you stated. That was my experience anyway. A hight animal fat diet, and weight training has helped a lot. I have anhedonia right now, and it's been 2 years since stopping the prami.
Can you please help me. I'm trying to figure out anhedonia on my own. I read on Wikipedia that pramipexole is, on the one hand, D3 receptor agonists, on the other hand, it increases dopamine in the prefrontal cortex. Which of the two things do you think helps anhedonia? I ask because I used to take latuda (lurazidone) and in low doses it relieved my depression and anhedonia. Lurazidone is an antagonist of D2 receptors, but it is an agonist of 5 ht1a receptors and therefore increases dopamine in the prefrontal cortex, as well as pramipexole.
broadly stimulating D2 or D3 receptors, or increasing dopamine in the prefrontal cortex, vital for depression and mood and positive emotion, will all have the potential to improve anhedonia. Another option i use antipsychotic-wise is low-dose abilify, which generally increases dopamine at low doses (ie 2.5-5 mg) and starts blocking it at higher dosages given its dopamine partial agonist properties.
Why not cabergoline? Compounding pharmacies can make low dose 50 to 125mcg capsules. (Or lower if needed) Cabergoline stimulates D2 receptors more as well.
honestly that would probably work, but has essentially no human trial evidence, thus pramipexole would be a more rational approach (from a doctors perspective since we try to stay within treatments that have at least a decent amount of evidence from RTCs). I just reviewed the literature on cabergoline and mood for humans in the past year, it might have been right around the time I made this video actually, and remembered being dissapointed that there hasn't been much research on it for mood in humans, if at all. In rodents it improved depressive-like symptoms and increased BDNF, so definitely lots of potential.
@@OllertonMD I have no libido despite TRT being optimized. I have autoimmune disease and immune system lower than it should be, so targeting dopamine receptors directly should work. I remember taking Cabergoline about 6 years ago and it did increase libido. However, it stopped working and I was getting side effects (I don't remember what though) I believe I tanked my prolactin level to zero. Prolactin has immune system benefits, so we want it at least in range. This time around I'm going to micro dose the Cabergoline to hopefully restore my libido and prevent side effects. I originally did 0.25mg twice per week, so that was way too much for someone without Hyperprolactinemia.
I have been experiencing this for years, like for a few months at a time. I see my doctor in 2 days and this is something I’m sure that she will be willing to try!
i hope you and your doctor are able to find something that works for you , whether that be pramipexole or something else. out of curiosity, do the months of anhedonia occur mostly during the fall/winter months, or does it seem random?
@@OllertonMD it is actually quite random. I have used a sun therapy light for years, maybe that's why it isn't more prominent in the winter. After looking into the medications, I know I'm not a candidate for them as I am currently experiencing kidney issues. I do appreciate you sharing this information
Love your channel, wish more Drs were interested in these topics. You mentioned you try Wellbutrin and low dose Abilify first. Do you ever combine the two? If so, are there any considerations for dose or side effects when combined? I'm taking 300mg Wellbutrin, 10mg Adderall, and low dose Testosterone HRT(born female, transitioning) atm and my Dr wants to add Abilify. I'm scared of taking too many meds together bc adding an SSRI and SNRI may have caused emotional blunting, which is persisting as anhedonia after stopping :( I'm also hesitant bc I found out a week ago I have very low vitamin D. I'm curious to give supplementing a couple months before more meds. but I'm not a Dr and Abilify may be safer than I'm assuming
thank you! I do combine wellbutrin and abilify frequently. I use smaller dosages of abilify when combining with wellbutrin though, as they both interact in the liver through a liver enzyme called CYP 2D6 and this can make abilify levels be higher than expected in the patient's blood, which will increase the risk of any potential side effect of abilify. So If I have 150 to 300 mg wellbutrin onboard, I make decide to use 2.5 mg abilify instead of 5 mg. Low vitamin D is very, very common if you live in a place/state in the US that is on the northern end of the country. Low vitamin D has historically contributed to my patient's apathy, fatigue, and anhedonia. I'm always a little surprised at how better patients feel when they get their vitamin D levels corrected. Personally, if I have a patient who's vitamin D is around 20 or lower, I'll prescribe them 50,000 units of vitamin D2 once or twice weekly for 4-8 weeks. This allows the vitamin D to corrected within weeks instead of the months and months it can take by taking 1-2k a day. Good luck my friend!
Regarding your low Vitamin D levels- I've been treated with a myriad of modalities for treatment resistant depression in Bipolar 2 for MANY years. I'm not a supplement/vitamin user at all, but did start D3 when I learned it was really low. Nothing has had a more positive effect for me than correcting this! Just wanted to pass this along as I thought it might be helpful. Best of luck to you!
@@wot4me2 Thats awesome!!!! I plan on making a video about vitamin D and depressive symptoms. I have had quite a few patients come in and I test their vitamin D and its low, often under 15, sometimes single digits, and I usually prescribe 50k units twice weekly for 2 months and some patients come back and say they have regained their energy and interest in doing things. Low vitamin D is super, duper common.
@@OllertonMD Thanks SO much for your comment, Dr. Ollerton! Low D is incredibly common; I wish everyone struggling with low mood would test it automatically- what can it hurt? : ) Looking forward to your video on the topic, and thanks again!!
@@OllertonMD thank you! that's helpful to know regarding the abilify and vit D dosing. I've started taking vit D and right away my sleeps a lot better. also noticed music is more enjoyable again. will keep up behavioral activation but I'm hopeful to see positive changes in a couple months
I suffer from "PSSD" after changing medication from Mirtazapin to Quetiapin, Agomelatin and Methylphenidat. Now after 3 month I take Mirtazapin again but it's not like before...i still suffer from erectile dysfunction but I'm not sure what's caused by the after effects of the change of medication and what's caused by anxiaty/depression (I think it's a combination). I'm afraid of trying other antidepressants, especially SSRI. I was thinking about to try maybe Ropinirol or Pramipexole cause they are discussed to may being a treatment of PSSD... Do you have any experience with the off-label use of Ropinirol/Pramipexole? My psychiatrist suggested Wellbutrin...I've tried it 3 times but I can not tolerate the side effects so this don't to seem an option... (Thanks and sorry for my bad english!)
I'm sorry you have suffered from this. I usually use wellbutrin for sexual dysfunction caused by SSRIs , but usually only when they are still currently on an SSRI. PSSD is rare enough that I haven't seen it yet in person. PSSD is a seriously under-researched problem so there are no evidence-based treatments for it. I have heard patients tell me that pramipexole does increase sexual drive and overall sexual health but haven't used it for sexual problems yet. I have seen or heard hypersexuality on pramipexole though, so sometimes the effects can be "over the top."
How does it compare to cabergoline? I tried cabergoline previously and I didn’t think it did anything much. Is there something particularly special about pramipexole for anhedonia, because, on paper, they look identical in how they work.
@@bobbypukes605 yeah they are both dopamine receptor agonists, I assume they would feel similar , but can’t say for sure since I’ve never prescribed cabergoline before since it is usually used for prolactinomas which I don’t treat as a psychiatrist.
I thought that the dopamine agonists aren’t used much in RLS due to the profound risk of augmentation of symptoms. Do you see anything akin to that with your anhedonic patients?
i have read some studies suggesting dopamine agonists can worsen RLS over years, probably due to repector tolerance. This hasn't happened with any of my anhedonic patients on it, but then again, I've only been prescribing it for a little under a year and a half. Its something I am always monitoring for though. thanks for the thoughtful comment. Tolerance is a significant risk of many psych meds. Especially SSRIs. I see those poop out on people fairly frequently.
The music at the beginning and end of this video gets stuck in my head, but it is a good stick because I find it calming. Can I find it somewhere? Thank you
haha thank you. that is high praise because I composed and recorded it myself in my studio :) I don't have it posted anywhere besides these videos on youtube
@@OllertonMD How cool is that? Guess I will keep watching and listening and then hum the melody the rest of the day. I do really like it. Thank you for creating the music and these videos
@@carojhig99 I was in a band in college called The May Reunion. If you want to check out my music, its on all the streaming platforms (last time I checked haha...we haven't been active in the band in a decade). The song "Blueberry" is one of the songs I'm most proud of. I am also proud of "Mountain." I was the singer, guitarist, and wrote all of the songs, usually with the help of my buddy and keyboardist Andy. edit: its still up! here is a link to spotify: open.spotify.com/album/6XkVc7c5Xkj8ZfltoYri7V?si=r5328DheTjmVdmCqLRm6Sg
Thank you so much for the link! Today was a perfect rainy day to listen to these songs. Blueberry and Mountain = beautiful. I have other favorites too. Music is so important and I love knowing of these songs.
I want to ask my doctor about this, but I’m nervous the answer will be no. I also am fairly certain I have restless leg syndrome (or is it just restlessness from depression/anxiety?) however, I do have adhd and she recommended taking Concerta for the Anhedonia. It helps me stay a little more focused, but I still don’t have enjoyment or pleasure. Do I even bother with trying Wellbutrin? Would I be good candidate for pramixepole?
I cant tell you which meds would be appropriate specifically for you, but I am always a fan of minimizing meds; I would personally tend to treat someone with anhedonia and RLS with pramipexole as it would help both. I have decent luck with wellbutrin for anhedonic depression, but not nearly as much success compared to pramipexole. I have yet to find a med for anhedonic depressive symptoms that works better than pramipexole.
How does this med relate to MAOIs, specifically Parnate? I was on a very high dose for 1.5 yrs and it helped a tad for a period of time & I got off because of side effects and no longer a benefit..
I’ve suffered from this all my life. It’s nice to know there may be a medical way out. I’ve had 3 ssri and they all made me feel numb to the point where I prefer my anxiety.
@@stefgreen5237 yeah tbh I’m not a huge fan of SSRI and rarely prescribe them for people that already feel flat emotionally as SSRIs appear to flatten moods, regardless of if the emotions are positive or negative
Hi I have something that I think you may find interesting or have some thoughts on.. so I’ve had anhedonia and broader emotional numbing for years now & something that reliably makes a big impact against it is clonazepam. It’s obviously not a great solution but I’m wondering if you could comment any thoughts as maybe to why it has such an effect? I can’t imagine its it’s anxiolytic property because when I’m not remotely anxious it still has the effect. Could this also be affecting the ventral tegmental pathway? Thanks in advance
That’s almost certainly from benzodiazepines ability to reliably increase dopamine signaling in the reward circuits like the VTA/ nucleus accumbens. Any drug that has reinforcing properties like benzodiazepines and opioids can boost dopamine. Benzodiazepines will cause rapid tolerance and a hellish withdrawal syndrome and can exacerbate anhedonia once tolerance or withdrawal sets in
Can the pramilexole promote healing of the dopamine system or does pramipexole need to be taken forever? I have tested this already and it does work but the next day I’m a zombie.
I wouldn't count on pramipexole doing anything positive for dopamine receptors long after you stop taking it. There is some interesting research showing pramipexole causing neurogenesis in a few small areas of the brain like the olfactory bulb (smell) and hippocampus but I don't think it will upregulate dopamine receptors long term. In fact, stimulating any monoamine receptor with a drug can downregulate them with long-term or excessive use. This is why its never a good idea to suddenly stop lots of psych meds-you need to give your brain time to upregulate any receptors that have downregulated during drug therapy
if anhedonia is caused by an antidepressant, it should generally disappear within a few weeks. For short or intermediate acting meds like paxil, effexor, zoloft, lexapro, celexa, I would venture to guess a week or so. If its from prozac, which is very long acting, it could be closer to a month since fluoxetine and metabolites like norfluoxetine are extensively metabolized by the liver and take about 30 days to be essentially our of your bloodstream. Some patients (none that I have had personally, but I've read plenty of stories online) believe they have long-lasting effects from antidepressants that cause numbness far after it is stopped, like PSSD. If this truly exists (I personally think it does, albeit very rarely), many people who believe they have PSSD not only suffer from longer lasting sexual numbness, but they often report emotional numbness as well, and important but neglected feature of PSSD.Out of the thousands of patients I've spoken to that have been exposed to antidepressants, none have reported long-lasting sexual or emotional numbness to me months or years after stopping the med, but that doesn't mean this rare phenomenon doesn't exist. One type of med that can definitely cause emotional numbness and anhedonia months after getting it are LAI antipsychotics (long acting injectibles) since these dissolve slowly under the skin into the bloodstream for 1 to 6 months after the injection. For this type of side effect from this class of meds, there isn't much that can be done unless a med is administered that binds to and aognizes dopamine receptors more intensly than the antipsychotic is able to bind and block them. This is one of the many good reasons to have a patient trial the oral formulation of the med for a few months before considering an LAI because once its in your body, thres no getting it out except by having it run its course.
Have you ever prescribed ropinirole (Requip) for anhedonia? I've tried it as it was more affordable and it worked faster for me (3 days) than pramipexole (5-7 days) but unfortunately it lowered my blood pressure too much even in low doses and when lying down. There was also a lot more drowsiness and sedation. I learned that it affects the sigma receptor in addition to the D2 and D3 receptors and drugs which affect the sigma receptor can cause more rapid relief of depressive symptoms.
I have yet to try Requip for patients, simply because pramipexole has better evidence for depressive symptoms. I appreciate you bringing up sigma receptors. This is a very neglected topic in psychiatry and plan on coming out with a video about it soon!
Can you please list some of the studies please? Thank you. My psychiatrist mentioned trying pramipexole but mentioned the possibility of compulsive behaviour.
heres a brand new meta analysis for unipolar and bipolar depression that I haven't had time to read in full yet, might be worth checking out: www.ncbi.nlm.nih.gov/pmc/articles/PMC10141126/ One notable thing I have read in this study glancing over it is that it appears compulsive behavior might be more of a risk for patients with Parkinson's disease than those with mood issues, which is good news! I've had a few patients that did have an uptick in desires to gamble and shop, but it hasn't gotten out of control for any of my patients on it yet. No idea why parkinson's patients would be more likely to experience compulsions than mood patients, but it might be that these PD patients might already be on other dopamine meds like sinemet or seleginine already The only pramipexole study I'm personally aware of that specifically addresses if it helped anhedonia was not published yet at the time. I straight up just emailed the guy in charge of the study and he said they did find it helped anhedonia.
I am not aware of natural dopamine *receptor agonists* (molecules that aren’t dopamine but nevertheless bind to and stimulate dopamine receptors) but there are various natural supplements that increase dopamine signaling in some way. The most straight forward of which would be straight up L-dopa, the direct precursor to dopamine , which is found in Macuna Pruriens. There is apparently enough L dopa in this supplement/food (it’s a type of bean) that a few studies show it might improve Parkinson’s disease.
Got prescribed this for RLS and got up to 1 mg. It made me have muscle weakness (I'm in my early 30s, man!), serious anhedonia, sleep attacks, insomnia, and other adverse symptoms. The augmentation was not fun. I even tapered down gradually to discontinue and got to less than .125 mg and still got dopamine agonist withdrawal syndrome. I was taking it with Parnate and was getting crying spells and brain zaps which I resolved with temporary dose reduction. Case in point, if you get an Rx, be aware of the risks, and keep your expectations realistic.
thank you for your comment. I agree, there are risks to every medication. Parnate + pramipexole sounds like a very powerful punch. I can see why this could be intolerable for some people.
is she a psychiatrist? if not, you might have better luck with a psychiatrist. If she is a psychiatrist, then that is just sad. Its sad to me how little even psychiatrists know or care about anhedonia, a pervasive, life-destroying symptom that often lingers even when other depressive symptoms go away with classic treatment options. You can also send her or print off this meta analysis to show her that it might be a reasonable option to try out. www.ncbi.nlm.nih.gov/pmc/articles/PMC10141126/
Hi doctor. Started pramipexole (augmenting with escitalopram) for treatment resistant depression or PSSD (not sure which exactly but I suffer from low libido and the cognitive symptoms i.e. emotional numbness, anhedonia, slow processing, etc). I started at a low dose 0.125mg and went up .25mg every 5 days, started experiencing more emotional numbness as I went 1.25mg onwards. Currently at 2.75mg, should I reach for the target dose 3mg or go low? And if u recommend going low, should the taper be at the same rate I went up or can it be lowered faster i.e. .5mg every 3 days or so?
Thank you for this information. Buproprion was the best anti depressant I was every prescribed all the way back in 2006-2008, but sadly after two years I took a grand mal seizure and had to stop taking this medication. Pramipexole has piqued my interest, I just don't want to risk another seizure - would this be an unlikely side effect?
I've looked into the risk of seizure from pramipexole and haven't found anything yet to make me believe seizure is a risk of pramipexole. I've successfully prescribed it to a patient that had severe, treatment-resistant epilespy and this patient never had a seizure on it
Impossible to say as I have only been prescribing it a year. I did have a patient or two that got up to 1.5 mg stop taking it without issue but they had only been on it for months. If you are on a high dose dopamine agonist for months or years and suddenly stop, I can almost guarantee most people will experience a withdrawal syndrome for at least 3-5 days. Fatigue, restlessness, sweats, probably anhedonia as well.
@@OllertonMD Oh okay, that makes sense. I have read some studies (admittedly I am not qualified to interpret them), where the patients experienced a protracted withdrawal (they may have been Parkinson's patients too). In some cases, it never went away until they went back on pramipexole. This concern is commonly expressed in various subreddits among people considering taking pramipexole for depression or anhedonia, so it could be worth addressing in another video at some point. It seems to me that many decide not to take it out of fear of "augmenting" their dopamine system in some negative and permanent way.
@@codeman55555 excellent points. I would love to make a video on DAWS. Do you by chance remember any articles you came across showing DAWS being protracted, or having PAWS-like qualities? I' havent come across any articles like that yet but would love to read them.
Hello, thank you so much for this video! I consulted with my psychiatrist, and he said that Parkinson's drugs are addictive. What is your opinion on this?
there is no known abuse or addiction potential to pramipexole that I am aware of. He might have been referring to the fact that dopamine agonists can make people compulsive with things like sex, spending money, gambling, etc.
the evidence is pretty scant on ropinorole compared to pramipexole. The most recent study I know of for ropinorole vs placebo for depression actually showed no difference between the two
Hey Doc, What do you know about the phenomenon linked with pramipexole known as augmentation (worsening of symptoms from baseline), specially in regards to restless leg syndrome I believe. A lot of people on RLS forums hate this medication and say it shouldn't be taken long term or at all. I sometimes get RLS if I take an antihistamine or some SSRI's so I'm just worried that if I start prami, somewhere down the line its gonna hit me with a worsening of RLS. Cheers
I’ve never heard the term “augmentation” used in that way. Augmentation in medicine means to add a new treatment to an existing one, ie like augmenting sertralinr with Wellbutrin. Maybe the forums are taking about how restless legs can worsen if you taper off of it too quickly after prolonged use? That is definitely a thing. This is true of most psych meds, ie having the risk of some sort of withdrawal syndrome if stopped too abruptly. I’ve never heard a patient tell me pramioexole itself worsened their RLS though. Antihistamines definitely worsen it for most people though, especially Benadryl which is an evil drug altogether haha
Augmentation is a common problem with all dopamine medications in restless legs. The same goes for pramipexol. Keep the dosage as low as possible and when it stops working, switch to rotigotin patch and if that fails too, switch to opioids....
If you’ve never heard of augmentation with Mirapex, I question your legitimacy and psychiatry. I’ve been on it for 20 years and I’m trying to tape back and it’s miserable. According to what I’ve read, it’s not the first line treatment for RLS any longer because of the severe side effects, the biggest being impulse control disorders. Anyone reading this, please do research beyond this video.
Ive tried pretty much every dopamine agonist and nothing has helped. Leads me to believe that there are more systems playing a role in anhedonia. Some research has stated the endocannabinoid and opioid systems may be involved
I feel quite confident opioid signaling is involved in hedonic tone; anyone that has been prescribed an opioid knows it boosts positive emotions. However, there are a litany of problems using mu opioid agonists for mood issues, such as tolerance, addiction potential, and the inevitable withdrawal syndrome that will occur trying to stop it. I personally believe kappa signaling is related to anhedonia and dysphoria. I am hoping there will be studies on kappa agonists for mood and anhedonia.
@@OllertonMD Thanks for the response. I really do hope some sort of fix is found In the future because it is an incredibly empty existence to not have emotions.
@@CheeseKransky12 hold in there friend. I have many patients who felt nothing for a long time and then and emotions started coming back. Its difficult because there are so many reasons someone can become anhedonic. Sleep disorders, brain inflammation, low vitamin D, poorly treated depression or PTSD...by far the most common cause I see is chronic anxiety. I think the brain shuts down the emotional processing regions of the brain to protect from the toxic effects of being fully exposed to anxiety or unresolved trauma. Just like dissociation is the brain's way of trying to disconnect one's consciousness from the full weight of severe anxiety or trauma, I think anhedonia is sort of a milder version of this protective mechanism.
@@CheeseKransky12 I'm sorry to hear about your anxiety and trauma. I don't know if you have PTSD or not, doesn't really matter, trauma is trauma and can manifest in different ways. Trauma very often requires a full course of some sort of exposure therapy, like EMDR or tf-CBT. Something to consider with your healthcare provider(s). I've seen my patient's lives absolutely transformed by trauma-focused therapy. Good luck my friend.
Hello sir. What are your thoughts on combining this drug with venlafaxine for long term treatment resistant depression, anxiety, anhedonia and suicidality? I was interested in trying an MAOI after trying ~8 SSRI or SNRI meds but MAOI are not available in my country. Right now my plan is to experiment with higher doses of Venlafaxine and potentially try Lithium augmentation. Any hypothetical thoughts on augmenting Venlafaxine with Lithium or Pramipexole? Thanks
combining venflafaxine with pramipexole is something I would certainly consider in some of my patients. When you bump venlafaxine high enough, ie 250-30 mg, it actually becomes a SNDRI, ie it starts also effecting dopamine at higher dosages. Adding pramipexole would then increase dopamine, which often relieves anhedonia, from two separate angles: the high dose venlafaxine would block the reuptake of dopamine at the synaptic cleft, and pramipexole would directly stimulate dopamine receptors. Another somewhat popular combo with venlafaxine is adding mirtazapine. Venlafaxine + mirtazapine is referred to as "California Rocket Fuel" by some psychiatrist. There are a few small studies showing its a good option for treatment resistant depression- assuming the person can tolerate mirtazapine's sedating effects that is good luck my friend.
I have abilify and it's 2mgs my Dr prescribed to me for add on to Prozac for OCD and I've been scared to ever take it , been saving the scripts for 6 months and just don't want to be on an antipsychotic medication but seeing that it can help dopamine makes me curious to try it
be warned that LOW DOSE abilify can INCREASE dopamine signaling, which for many people with OCD, will worsen their symptoms. It is generally thought that BLOCKING dopamine signaling is the key to antipsychotics efficacy in OCD. Abilify for most people probably won't start blocking dopamine receptors until they get past the 5 to 10 mg range. Risperidone and seroquel have better evidence in OCD than abilify. you should always feel free talk to your doctor about your concerns and I hope you and your doctor can get your symptoms to a more comfortable place. OCD can be the worst!
@@user-sf3qr6jt9j I have OCD and the pramipexole made me more impulsive because it increases dopamine in a different way. Definitely not something to take for OCD. Hope your OCD gets better for you
@@user-sf3qr6jt9j doctors will usually treat both with high-dose SSRI. Unusually high dosages of SSRIs don't usually improve response rates for depression, but high to very high dosages (ie 100+ mg fluoxetine, 300+ mg sertraline) are often vital to get a handle on OCD. Meds like pramipexole will potentially worsen OCD for a significant percentage people, although this is theoretical and hasn't been actually tested. Great question btw! PS/random thought: for those that don't tolerate high dose SSRI, I often consider NAC, a supplement that appears to improve OCD in various studies. NAC is nice because besides smelling/tasting nasty, tends to have little to no side effects for many patients
I don't think I would say that as a blanket statement as it depends on the situation, but I would say its probably true for many patients. One one hand, MAOIs have much better evidence of efficacy since they are FDA approved specifically for depression. The benefits of trying pramipexole first though are numerous: 1. On pramipexole, eating certain cheeses, fermented foods and alcohol doesn't make the patient risk death, stroke, etc. There are very strict dietary restrictions on MAOIs given tyramine "cheese effect" 2. For most people, pramipexole will be more tolerable AND will be much less dangerous mixing with other psych meds. 3. A psychiatrist will generally be much more likely to prescribe pramipexole than MAOIs given the above and that it takes very little MAOI in overdose to kill someone
Hi doctor. I would like to know if sertraline (50mg) or paroxetin 75mg, can help to over come this. What other things do you recommend to do to overcome this naturally, easier and quicker? Thanks a lot
just like any med, it totally depends on many factors. it certainly won't have any effect on anhedonia after you stop taking it though, unless the pramipexole lead to one starting a bunch of goals and hobbies that they then continued after cessation (since Behavioral Activation itself can be a treatment for anhedonia)
I’m hopeing this drug is not like a Modafinil type semi stimulant drug. Do you feel this drug, maybe with a low carb ketogenic diet would improve anticipatory anhedonia, severe slowing and sluggishness, alogia and other negative symptoms increase episodic memories? Do you see any use in “self-disorders/ipseity issues” Wellbutrin or aeuviliy really doesn’t work for anhedonia, wondering exactly how Pramiprexole works for mood as well in schizoaffective related issues with mainly severe negative symptoms, mood symtoms, disorganized symptoms
unfortunately, pramipexole can worsen psychotic symptoms, but not always. Pramipexole is not a stimulant and doesn't cause a "jittery buzz" like classical stimulants or modafanil and does not keep people awake. I've had remarkable success for treating anhedonia with it though. The three main meds I use for anhedonia is wellbutrin, low dose abilify and pramipexole. Good luck my friend.
@@OllertonMDmy issues are really the residual issues of anhedonia and negative symptoms after a first episode psychosis many years ago. Aerobic exercise has consistently always helped my type of anhedonia….but at some point I would like to move on and not have to rely on it and yes…have always been looking for that equivalent excersise in a pill type drug. Is this anything like that by chance or similar in terms of BDNF and its effects on mood? Thanks Doc, glad you are having success with this med
@@Lipolimtown I've seen 2 rodent studies saying pramipexole increased BDNF, and 1 study that claimd the oppostive, so I'm not sure if it increases BDNF. The best evidence for increasing BDNF is SSRIs/SNRIs (which can worsen anhedonia sometimes), exercise, and antioxidant foods like berries. I'm msorry to hear about your episode of psychosis btw :( Exrcise appears to not only increase tonic dopamine levels, but also upregulates dopamine receptors, which I think is more important. I'm glad exercise has helped anhedonia!
Sir, i suffered with major depressive disorder, i used desvenlafaxine, now my symptoms decreased as much as 70percent, but i am still unable to feel pleasure in many activities, my doubt is i used desvenlafaxine, it can increase serotinin and norepinephrine, but it didn't increase dopamine that's why i am unable to feel pleasure. Sir can you tell me how many months should i take pramipexole and stop it
if you had anhedonia before starting desvenlafaxine, then it probably isn't the cause. if the anhedonia worsened on the med, then it is probably contributing. you are correct that this med wont substantially increase dopamine, and actually boosting serotonin with antidepressants can blunt dopamine signaling in the brain and can indeed make anhedonia or a loss of positive emotions worse. You are not my patient so I can't make any recommendations about medications or any treatment. What I can say is that any medication for anhedonia will only work for as long as you take it. So some people might have to take pramipexole for 3-6 months, some might take it for years, it just depends on the patient
I have been suffering from severe depression for 8 years, anhedonia and total sexual dysfunction for about 1.5 years. Bupropion was always the only one that helped me, but it stopped working after a few months. Now I'm trying pramipexole, I'm on a dose of 0.5mg for 1 week and still disappointing. I feel sick, , mild nausea, but it has a completely different effect than buropion. My sexual dysfunctions even got worse. But I will try to persevere and increase the dose again. Apparently this drug is my last hope.
nausea is somewhat common when starting pramipexole and dopamine gonists in general. There are many millions of dopamine receptors lining your gut lumen that can increase the movement of the gut and cause GI upset. This is why some ant-nausea meds do the opposite of pramipexole and block dopamine receptors (like metoclopramide). Sometimes the nausea gets better once your gut lining gets used to the extra dopamine signaling. 0.5 mg is not usually a dose I see help anhedonia in my practice. Usually 2-3 mg, if the patient can tolerate it. I'd talk to your provider about your anhedonia some more if pramipexole doesn't work out for you. There is ALWAYS hope. even if you have tried spravato, there are other options. Anhedonia can likely be caused by unresolved trauma/PTSD, sleep apnea, medications (like SSRIs, antipsychotics, mood stabilizers, lithium,), chronic inflammation (which can be explored by getting a CRP lab, which is easy and cheap to get, and in most states, a person can order it themselves online), high generalized anxiety, etc etc. I've seen anhedonia get better with ketamine infusions, (which of course hits differently than spravato), TMS, ECT, CBT, getting CPAP for previously undiagnosed OSA, etc. There is always hope my friend. And please always make medical decisions under the care of a licensed medical provider. Stay strong my friend, and thank you for your comment. Dr O
@@OllertonMD To be honest, I'm a little disappointed with this medicine, I really don't have any nausea at all. I have similar symptoms like flu, fever, sweating, strange smell of sweat. I would accept all of this, but I am most disappointed with how it affects my sex life. I've been suffering from serious sexual dysfunction for a year and a half and I expected this medicine to help me with it, but it made it even worse, I don't even have nighttime erections anymore... At the same time, dopamine agonists are supposed to cause hypersexuality, so why do I have to suffer again? Bupropion was much better in this regard, after a few days I could feel my sexual functions returning, but here it is the exact opposite. I'm currently on 1mg... Dr. Thank you for your answer, at least I see that you care about patients and suffering people.
How long does it last if someone doesn’t take medication I don’t want to take any medication. I got it from substance abuse for over a year and when I stopped, I don’t feel any pleasure at all. Craving crack again
IIRC one study actually did brain scans of cocaine users and found their dopamine/reward circuitry didn't get close to normal until potentially about 12 months. Depends on how much cocaine was used and for how long of course. Sorry you are feeling bad my friend, hang in there
Beautiful oh god dude if this works. My Anhedonia is so bad and is because of weed trauma depersonalization derealization dissociation. Please keep up with your work we need you so much 😔. Question is it possible for the development of such a drug that gives permanent fix?would prefer detailed answer thank you
thank you for the comment. Please note that continued cannabis use or having unresolved trauma (trauma that hasn't been processed in trauma focused therapy like a full 3-4 month course of EMDR or tf-CBT) will probably dramatically decrease the odds of any medicine, including pramipexole, to work for anhedonia. unfortuntaly I don't know of any drug that can perminently fix anhedonia. If such a drug were to be designed, it would have to increase neurogenesis in the reward system or somehow increase dopamine D2 and D3 receptor density. The closest thing I can think of that can or likely can do both of these is daily, chronic exercise and avoiding things that can downregulate dopamine receptors, like cannabis and other substances that hammer dopamine receptors. Good luck my friend
Same bro had dip dr for 30yrs straight and the 1st time and only I felt like I had a normal brain was adderall but only lasted for a half hour, then back to the mind in hell. But what I felt was when I was like 14 when I remembered how normal felt now in my 40s and been trying to figure that way back out again…it just game me hope to start looking for new meds so if I can get my doc to get me this mirapex it’s worth a shot…I’m with ya
@@Bran317 good luck my friend. On average, dopamine meds probably offer the best odds of improving anhedonia in most people, along with anti-inflammatory medicines if brain inflammation is the cause
MAOIs are essentially never used anymore. I have yet to prescribe one and never had a supervising physician in training that was willing to try one on.a patient of mine, so I don't really know. There is essentially no real-life training on MOAIs in a psychiatrists training. I do know that seleginine and pramipexole are used in Parkinsons disease together sometimes. Theoretically, I don't see why it would be dangerous. Combining MOAIs with serotinergic medications is very dangerous, but pramipexole is a dopamine receptor agonist, so it is probably safe but have no real-life experience doing that. Definitely talk to your prescriber about this before trying something like that. In terms of monotherapy, I use pramipexole alone frequently, and works great most of the time
I think my longest run on a patient with pramipexole has been somewhere between 9 and 12 months. I started prescribing it last year while I was still a resident. Haven't had it poop out on me yet, unlike antidepressants, where that happens pretty frequently
even with genetic testind done that shows i have 8 times less dopamine, it has been almost impossible to get doctors to prescribe anything like Abilify or Mirapex until i mentioned i do have restless leg issues. so now i know after years of telling doctors what i needed that i was right and they were wrong. story of my life. its insulting that doctors think people who live in Mexico or thailand are smarter than us living in the USA and yet those people can walk into a pharmacy and get whatever they want in most cases but here in the usa we have to beg doctors. spend the most in the world on medical care and have horrible horrible health in general. big pharma owns us. F that
I’m currently taking adderall as it has been the only thing to do anything. However I’m still bed ridden. Is trying prami along with the adderall I’m already on a bad idea? Thank you so much for any insigh I think my dr is willing to give it a try just didn’t think I should come off my stimulant as I would be comatose without it.
can't give you medical advice, but can tell you I've added pramipexole to adderall without issue in the past. One increasing actual dopamine levels, and one increases signaling at D2/D3 receptors without actually increasing dopamine. So there isn't an absolute contraindication to combine them in general.
@@OllertonMD of course tysm for the reply, i understand to speak with my dr. I just wanted another opinion he said the same thing. Wanted to ask one more question. Have you ever considered l dopa as a treatment? I know it is another treatment for Parkinson's like prami. Wouldn't this have less side effects and a similar effect
@@Timayy I actually have considered it, but haven't tried it yet due to a lack of clinical evidence/human trials. I assume it would work though. Anything that increases dopamine or dopamine signaling in the CNS should improve anhedonia. I don't think l dopa would have less side effects than pramipexole though, as l dopa will cause side effects "below the head" (Ie cause side effects in the body before it reaches the brain). It would probably work better and potentially have less side effects by combining it with carbidopa so it doesn't metabolize and interact as much with the body before reaching the brain. Ie, Sinemet would probably be a better option, similar to how sinemet aka carbidopa/levodopa is usually used together in Parkinsons. Luckily, sinemet is widely available and is a very old drug and thus very cheap. I'll consider using it if pramipexole doesn't work for a patient. Other experimental options I've considered is cabergoline or bromocriptine.
@@OllertonMDmy dr is recommending the sinemet 25/100 mg once daily as he believes it’s due to an inborn error of metabólica with bh4 deficiency. My csf hvaa bh4 and forgot the same of the third was low. Wanted a 2nd opinion if u think the adderall is safe with the sinemet. He seems to think it is of no concern. I could let you know how it goes
@@Timayy I've never prescribed simemet so I have no personal clinical experience with combining the two. I would guess that the two together could be quite stimulating. Both stimulants and sinemet can increase blood pressure so if the two are combined, blood pressure would need to be monitored carefully. If your doctor thinks you have a BH4 deficiency, you should ask your doctor about methylfolate supplementation though. Its going to be hard, if not impossible, to have normal methylfolate levels without adequate BH4. Luckily, OTC methylfolate has become quite cheap compared to 10 yrs ago. Methylfolate is essential to normal production of serotonin, norepinephrine AND dopamine. I used methylfolate for treatment resistant depressive symptoms sometimes.
I’m not familiar with any literature showing untreated psychosis causes dementia specifically, but is has been associated with worse cognition generally, and there is also concern it can also worsen the course of the illness, make psychotic episodes more likely in the future, and might also worsen the more depressive or “negative symptoms” of schizophrenia long term which is a big deal since negative symptoms predict decreased quality of life and increased disability more so than “positive symptoms” like hearing voices and being paranoid or delusional. Psychosis, like mania, is thought to be neurotoxic if it continues untreated. This is because Positive symptoms are much easier to treat than negative symptoms and cognitive problems in psychotic disorders. Antipsychotics are quite effective for many people to suppress things like hallucinations and paranoia but not so great with treating cognitive problems and negative symptoms like avolition and anhedonia
yes. occasionally. Hasn't happened to any of my patients though. its actually often used to prevent wear-off dyskinesias in those with Parkinsons disease that are taking levadopa
Sir can this drug be titrated in 0.5 mg every say 4 days with a target of 3 mg? Im currently on 1.5 mg with a .25 mg increase every 4 days and very desperate. No improvement as of yet unfortunately 😔
it all depends on the patient's tolerability and what the prescriber is comfortable doing. I usually increase by 0.5 mg every 14 days, and most patients tolerate this schedule and dosing regimen without issue. This is probably in part due to the fact that my patients that don't tolerate pramipexole know they don't tolerate it right when they start it. AKA if my patients have little to no side effects at 0.5 mg - 1 mg, they usually tolerate higher dosages. The 3 side effects I see that make patients stop it is GI distress, dizziness, or sedation. Besides one patient that had modestly increased urges to gamble, I actually haven't come across any of the more "unique" side effects of pramipexole like psychosis or compulsive behavior. Good luck my friend, I hope you and your doctor find a treatment plan for you that brings the color back into life.
yeah unless one of my patients have a psychotic disorder, I keep abilify to 5 mg or under. At this dose it can boost dopamine and improve mood and motivation. But once you get to dosages of 10-30 mg, it runs a much higher risk of classic antipsychotic side effects like EPS, sedation, etc. The most common reason my patients decide to taper off abilify is either restlessness or sedation. Occasionally I've seen it increase weight 5-15 lbs too, but that's usually for patients that are on antipsychotic dosages. Thank you for your thoughts, Dr O
yes it does. ECT improves pretty much everything about depressive symptoms and is the most effective treatment for depression that has ever been found. pubmed.ncbi.nlm.nih.gov/35764228/
Hello sir, I have porn induced anhedonia. I was compulsively watching pornography for many years and I believe my dopamine/reward system is very worn out as a result of extensive porn usage. I have experienced anhedonia and depression as a result of this. Do you think pramipexole would help alleviate those symptoms? Thanks in advance, I am looking for answers as this condition is drastically effecting my life.
assuming you anhedonia truly is from compulsive pornography use, have you tried sustained abstinence from porn? This is purely anecdotal as far as I am aware but lots of people on reddit and other forums claim sustained abstinence resolved the emotional and sexual numbness they attributed to pornography. Theoretically pramipexole should help with any condition where dopamine 2 and 3 receptors are not being stimulated enough
@@OllertonMD Hi, thanks for your response! I feel very confident that my anhedonia is resulting from compulsive pornography use. I am normally a very upbeat person who has not had many mental health issues throughout my life. I have only had depressive episodes once I started compulsively viewing pornography. I have tried sustained abstinence and I would say after one month of abstaining symptoms subside dramatically. Managing stress is difficult for me and life events make me prone to relapse. Abstinence is difficult to achieve when dealing with depressive symptoms.
@@Venomenon1000 hold in there man. if you feel like porn use has had a detrimental effect on your life you might want to speak with your primary care doctor about seeing a therapist that specializes in compulsive behaviors. There is little evidence empirically to support this last time i checked years ago, but theoretically, anything that hammers dopamine receptors excessively can probably cause emotional blunting, and removing that stimuli long-term might allow the dopamine receptors to upregulate to normal again. Chronic stress is a widely accepted contributor to anhedonia as well, and many rodent studies show this (ie stressing out rats over and over, like shocking them unpredictably and repeatedly, or putting them in a cage with an aggressive, unfriendly rat, causes depressive symptoms and reduced sugar water consumption, which is used as a surrogate for anhedonia). Managing stress and seeing a therapist for porn use that is disrupting one's life might help, but ultimately, I cant give medical advice to people that are not my patients (I've got to include this disclaimer). I wish you the best of luck and hope you are able to live the life you want to live and I hope you start feeling better soon!
It also down regulates dopamine receptors, what goes up must come down especially with this medication. Medication I've tried it. It did help me come out of a slump
i agree tolerance is a concern for most psychiatrist meds. that's why I am always trying to walk the thin line of the Minimally Effective Dose. If someone has low dopamine signaling (which is practically impossible to ascertain in humans besides those that get a DAT scan, which insurance will usually only cover for those undergoing a Parkinson's Disease evaluation with a neurologist because of cost), theoretically, a minimally effective dose might be able to return someone to normal dopaminergic functioning without running the risk of tolerance.
usually within 2-4 weeks, and fully kicks in by ~2 months. If you are on low-dose abilify for something like depression or anhedonia, I often see people start feeling better after 5-7 days. It takes about 5 days for psych meds to reach "steady state" in the blood, but the full effects take taime. Good luck my friend.
ideally no one would have to take any drug for any reason, but that's just not the reality for most of my patients, even when I recommend lifestyle change before considering a med. Most of my patients are unwilling to do much in terms of life or behavior change and just want a medication to help them feel better. trust me, I try.
the problem with this drug is that you need to reach atleast 1-1.5mg for it to work and it may never even work and you may need combinational therapy such as Nortryptiline 25mg addon or bupropion or even both
yes most people will need at least 1.5 mg in my experience for it to be noticably anti-anhedonic. The sweet spot I have found for most of my patients is 2-3 mg. Some studies have gone up to 5mg but I've never had to go over 3 mg. Combining with wellbutrin would probably be an awesome combo. I've started pramipexole in those who had already been on wellbutrin for years, but have never started both near the same time, but maybe I should. Wellbutrin happens to be my favorite antidepressant actually. Thanks for the comment!
it can *potentially* make both worse. Boosting dopamine signaling in general, but especially dopamine receptor agonists, can increase compulsive urges/ behaviors to do pleasure-seeking behaviors. But everyone responds differently. Compulsive sexual behavior is a known risk of pramipexole though.
Modafinil doesn't just boost dopamine but serotonin as well, so YMMV. I got similar bad reactions from it as from SSRIs, i.e. stomach upset and migraines.
the mechanism of modafanil is actually mostly unknown, so hard to say. Its usually just used for excessive daytime sleepiness. I've never prescribed it for anything other than that. Maybe someone that has been on modafanil can chime in.
Any reason why you don’t touch on some of the other benefits(particularly sexual benefits), like lowering the refractory period in men, potentially boosting libido and sexual quality as a whole
this video was meant to focus strictly on emotional anhedonia, but ejaculatory anhedonia and overall sexual dysfunction is definitely a widespread problem. I've never used pramipexole for sexual problems in my patients but I have had a friend or two tell me it reversed their sexual dysfunction from depression or SSRI treatment. will start asking more patients about if pramipexole has improved their sexual health or reduced the refractory period, as this is an interesting area
@@OllertonMD it’s an extremely interesting component of this medication. I myself do not suffer from depression or anhedonia. But I personally use a low dose of pramipexole to lower my refractory period in bed. It’s been great in doing so. I highly recommend gathering more intel on this use case as well. It’s something that people commonly struggle with, especially as they grow older but would still like to continue having sex as if they were 21 again
Hopefully I can convince my doctor that I need a prescription for this. anhedonia/apathy/depression + (all stimulators are banned in my country even Bupropion) = living in hell
@@minepolz320 Tell me my friend, how did you become anhedonic, did you use antipsychotics or benzos before? because the cause of anhedonia and the remedies you can research you will find many cases of people like this, don't take buprione it will only make it worse
@@OllertonMDI started taking pramipexole, but unfortunately it just makes me very sleepy, so much so that I can't even stand on my feet. is it worth continuing? in any case, it didn’t make my anhedonia worse, but on the other hand, I don’t quite see any positive effect, now I’m 1 week on a dose of 1mg, just if I’m not mistaken, then agonism to D2 dopamine receptors reduces the release of dopamine causing this side effect
this has only been done in research studies. there is no routine brain scan used to detect anhedonia. I doubt it will ever become commonplace since anhedonia is simply uncovered by the endorsement or denial of a medical symptom by the patient- if someone has a decreased or absent ability to experience pleasure from activities they used to enjoy, that is anhedonia. Some studies have used fMRI studies to show how strongly the reward circuitry lights up during rewarding events, or checking the functional connectivity between the reward circuitry and other regions of the brain.
theres been little study on this topic but so far the evidence has been mixed. One negative study on levadopa in anhedonia was in cocaine addicts though, so take that with a grain of salt, as cocain addict's dopamine receptors are profoundly donwregulated. I would supposed levadopa would help people's anhedonia if their anhedonia is caused by low tonic dopamine levels
ive got 20 anhedonia video ideas i am working on. just recently moved my office space into a new room so hope to be up and running in the next 2 weeks!
@@OllertonMD Thank you so much. I've tried just about everything. Selegiline, rasagaline, pernate, wellbutrin. Nothing works, or causes really bad side effects.. Prami worked somewhat and restored my libido but was side effecty for me. Looking forward to more content, almost nobody talks about this stuff.
just in montana for now. I am starting an insomnia telemedicine service with a few friends and we hope to give access to as many patients in different states as possible and once that is up and running, if our system of providing online insomnia treatment works, I I hope to then start an anhedonia clinic online in as many states as possible. AFAIK, this would be the first anhedonia clinic in the world. I'm guessing this is a few years out though.
@@nicolavowles2930 unfortunately I wont be able to see patients outside of the united states due to licensing laws in the United States, but I hope to come out with an ebook and udemy course people can take for those that are unable or cannot afford to see me. I plan on also posting a free pdf soon of promising medications and labs anyone in any country can bring to their doctor that might help them heal from anhedonia
or maybe in the future if the clinic is viable, I can hire practitioners in other countries that I train that can be the providers for patients outside of the US. Come to think of it I really like this idea. We will see how things pan out! Currently have another 1.5 yrs of my current contract I need to fulfill at my normal 50 hrs a week job so will probably be in a few years, but I hope to come out with other material people can read and watch in the meantime. I'm currently converting a room in my house to a video studio/workspace so I can get to work on this stuff soon!
This is the most in depth video on Prami that I’ve seen.
thank you! yeah i started this channel some years ago because i realized there was a dire need for a doctor to explain meds to people in a way that is evidence-based but also in plain english. your comment is music to my ears. Going to start cranking out a video every week starting next month! please let me know if you have any meds you want me to talk about in future videos.
First off, THANK YOU for your desire and effort to serve this underserved community. Our son has severe, treatment-resistant depression and anhedonia. He recently went off his Prozak because he was sick of feeling 'nothing', but now needs a new approach. He hasn't had a psychiatrist in many years, after his last one's MO was a 3 minute interview followed by throwing drugs at him based on drug company kickbacks (I'm not being facetious, he was actually convicted of that). Finding a psychiatrist who is taking patients is hard enough. HOW do we find one who has a specialty or desire to work on anhedonia cases instead of just the 'run of the mill' practitioner? The psychiatrist search engines do not include a place for specialties or keywords.
im so sorry to hear about your son. I can only speak from my own lived experience, but I haven't met any psychiatrists that specifically try to treat anhedonia. They all just assume It will get better if you treat it like just one more clinical depression symptom. Sad truth is that commonly prescribed antidepressants often worsen anhedonia. Prozac, as a potent SSRI, will very often flatten mood and cause the "nothingness" you are describing.
I have found adding pramipexole to an SSRI, or just prescribing it as monotherapy, can alleviate anhedonia. It can be hard to find any doctor, PCP or psychiatrist even, that will do this though.
For severe, treatment-resistant depression, I'll often refer them for ketamine, esketamine, or TMS. I've seen miracles with all three of those, and they work QUICKLY when they do work.
I hope to come out with an ebook that includes all potential options for anhedonia; things people can try and also medications and treatments they can talk to their doctor about.
@@OllertonMD Thank you for your reply Doctor. We appreciate your thorough response. Our son has tried Ketamine (injected) and is currently doing esketamine. The injections had a more profound positive effect than the esketamine is having, but it didn't last and was too expensive to continue since insurance won't cover it. He will likely try TMS next, though we are again having trouble finding doctors to support him in our area. Thank you.
You need a neuroscientist/pharmacologuist to help you. Fluvoxamine is like Prozac but less emotion blunting. Wellbutrin also does the same thing but also increases adrenaline more.
I have anhedonia after a bad reaction to fluoxetine. I had akathisia and was awake for 10 days straight because of the restlessness, terror and pacing. I also had jerking limbs, non stop diarrhea and other symptoms. Ever since this reaction I am left with severe anhedonia and sexual dysfunction. I can’t feel music, and all my hobbies and things like socializing, movies, video games, reading, sports, sex, eating etc are all completely flat. I also lost all motivation since nothing feels good or rewarding anymore
I feel hopeless and don’t know what to do or what to try. I just want to be able to feel pleasure again and have motivation to live a happy life again.
I’m not sure why I had this reaction since I was on high dose fluoxetine in the past for OCD and it was helpful with minimal side effects.
It’s been 2 years since then but I’m not any better. Part of me is terrified of trying medication again but I feel like things won’t get better on their own at this point either. I’ve looked into things like Wellbutrin, MAOI’s, pramipexole, low dose Abilify, lyrica etc but haven’t tried any out of fear and low motivation.
I am so sorry man that sounds absolutely horrifying. I hope you have or can find a good psychiatrist who can guide you through different options. Hold in there my friend. There is always hope.
I'm in the same boat 🙏
@@OptimizingSpiritYou had a bad reaction too?
@@user-sf3qr6jt9j yes I did but mine was from finasteride propecia and have had anhedonia for 24 years and still ongoing. Have tried pramipexole and it didn't cure me, it helped a bit with motivation but it also has a down side it down regulates your dopamine receptors so once you stop using it it's even more difficult to feel pleasure
@@OptimizingSpirit Hello, I have severe anhedonia after taking benzos I stopped them all and take vitamin and omega 3 can you help me with some food or supplement that helps me improve please help me 🙏
thank you a lot doctor, i'm from iraq, I suffered from anhedonia 6 years ago, when I started taking fluvoxamine for OCD. After ten days of taking it, the OCD went away, but also all my personal feelings and pleasure went with it, and I immediately developed peripheral neuropathy, and it was confirmed by a neurologist and an EMG. I'd rather have OCD than this hell. Anhedonia varies in severity depending on behavioral activation, but it remains a bad thing. You have given me great hope that there are medications that can help. Thank you again.
I have a question, doctor. It has been shown that I have a significant deficiency in vitamin D3 and folate, as well as a significant deficiency in testosterone. “I am male.” Can these things cause anhedonia? Also, can nerve inflammation lead to anhedonia? What do you recommend to treat inflammation?
@@artspace1435 I'm not a doctor, but low testosterone levels can definitely cause anhedonia
in my experience vitamin D can cause anhedonia (patients describe it as lethargy, no motivation) and low testosterone can definitely cause a loss of positive emotions. Not sure on the folate one, folate deficiency is pretty rare in my country given it is added to flour. Theoretically it might though; folate is essential to create methylfolate which is needed for adequate neurotransmitter production, including dopamine.
Sounds like pssd. I have it and so do countless other people. Do you still have issues? Have you healed? Not a doctor
thanks so much for the specific, concise information. Ive suffered from BP II for decades.
I have prescribed pramipexole to patients with BP 2 repeatedly, usually with good effect. good luck my friend! the risk of switching to hypomania on pramipexole appears fairly low
Those Compulsive behaviours are the exact same as bipolar mania !!!!.. which is great, till you get to the uncontrollable rage stage and become violent
luckily, pramipexole has successfully treated bipolar depression in many instances with a low rate of switching to mania. But if someone is bipolar and on pramipexole they should be on "oppositional therapy" to prevent mania anyways, ie lithium, an anticonvulsant or a 2nd gen antipsychotic. thanks for the comment!
After 6 years of chronic depression and Venlafaxine, I developed severe anhedonia which progressed into a negative/cognitive schizophrenia-like state. I suspect the venlafaxine nuked my dopamine but I cannot drop it because of depression. Would taking Pramipexole and slightly lowering Venlafaxine make sense? I don't have any history of psychosis or OCD.
Great video as usual.
As someone who is suffering from this since years I have a few questions:
1. Do you (generally speaking) recommend trying MAOis before Pramipexole?
2. Do you think a similar effect can be reached by long-term practice of mindfulness exercises?
3. The only short term relief I get is from caffeine, especially after I've withdrawn from it for a few days and then start drinking coffee again. Thoughts on that?
4. Some people recommend ketogenic diet, would you recommend it?
1. I would usually not try an MAOI before pramipexole in any of my patients
2. Mindfulness reduces anxiety and might increase tonic dopamine, so this is a reasonable option for many people to try, especially since chronic unpredictable stress is a major cause of anhedonia
3. Probably due to dopamine increase, and it helping after a break is likely from dopamine receptors upregulating during cessation
4. at this time I don't recommend keto diet to my patients given the lack of evidence it improves mood, and VLC diets have been shown to worsen mood and anxiety in many people, although most of these studies weren't specifically about being in ketosis as far as I understand. A plant-focused or mediterranean diet has much better evidence of being able to improve mood, such as with the SMILES tiral
hope this answers your questions!
Go for the MAOI.
@@OllertonMD "1. I would usually not try an MAOI before pramipexole in any of my patients"
Good day, sir. Could you elaborate why, please?
@@Zigoliokas MAOIs are very rarely used anymore given its extremely narrow therapeutic index (ie the dose needed to help is uncomfortably close to the dose needed to harm, or kill). A 2 week supply taken all at one, if someone were suicidal for example, is enough to kill someone sometimes.
Also, unless you are going with low dose Ensam, MAOIs require a very strict diet to avoid the "tyramine cheese effect" or hypertensive crisis. MAOIs also often cause pretty significant dizziness and low blood pressure. Also, you can absolutely not be on any meds or supplements that increase serotonin syndrome, so a patient would have to be completely off antidepressants for 2 weeks before an MAOI is considered.
So overall, MAOIs are much more difficult to prescribe and take compared to pramipexole.
I am not against MAOIs at all though btw. I am very open to prescribing them in the right patient. It would have to be a patient that has not had SI in years and has never had a suicide attempt, esp via overdose attempt. And the patient would have to be high-functioning and motivated enough to follow a very strict low-tyramine diet, and not be on any other serotonergic med. So I just don't have many patients that would qualify. But if I find the right patient, I Would be excited to consider one. I am really the only psychiatrist I know in real life that ever even really considers them an option. Most psychiatrists would refer to ECT before trying an MAOI, which seems over the top to me in many cases.
Last question. Extended release or immediate, which one is better for anhedonia? THANK YOU! ❤
This is awesome information! And from a very credible source! I trust Dr. Ollerton with my life! he is wise beyond his years and exceedingly smart!
Agomelatine or Pramipexole which would be better in treating anhedonia induced due to SSRI Escitalopram in term of long term side effects .
DR, reading around I was struck by a few results that showed diminishing returns from pramipexole for another atypical (but likewise arguably very reasonable in theory) use, as adjunct to methylphenidate for ADHD. The papers in question showed significant improvement relative to standard methylphenidate treatment on all scales -- until six weeks of the study. At the 8, 10, and 12 week marks these results curved back down to insignificance and eventually began to throw up some insignificant, but potentially suspicion-raising results of impairment relative to methylphenidate alone. Central dopamine homeostasis seems to be a fickle beast!
This is all to say -- can I ask if you have encountered, in your anhedonia patients, an insensitivity to the therapeutic effects against anhedonia that develops after a time? If so, was there a strategy in response? Or have you on the contrary not seen any problems of insensitivity developing to these antidepressant effects in your pramipexole patients over time?
Thanks so much for your informative video!!
very interesting question. The longest one of my patients has been on pramipexole that I prescribed specifically for anhedonia has been a little under a year, so keep that in mind- but none of them have built a tolerance to its anti-anhedonic effects yet. it could be that any focus-enhacing effects from dopamine agonists wear off over months though, like the studies you cite suggest. Although I think risk of tolerance is going to be dramatically higher mixing a stimulant with a dopamine agonist than either one alone- mixing an amphetamine or methylphenidate drug with a dopamine agonist is a very intense combo
Hey I was looking for a answer to my DP DR disorder with many more to and but anyways my doc started me on adderall and the first time I took it my brain went to feeling like I did 30 years ago when I felt real and haven’t felt normal and n hell every day since,but was just probably about 30 minutes my mind was clear remembering everything and was in tears because it’s been so long sine I was a real person…I know you probably don’t understand my writing but I wish there was a way to contact you or do some trial’s on my crazy mind and views…idk idk just saying there might be a link to that medication and the ones I’m on
I've had anhedonia for 15 years or so. It doesn't let up, I enjoy nothing except sleep. Ive tried many many depression meds several times over. They don't work. Are you able to write a script for someone on the internet, or can you give me a referral for it? Please, this has taken a majority of my life away from me, and the thought of living another 30 or 40 years with this is terrifying!
Hi, I live in Germany and all the doctors that work on(get paid from) public health insurance don’t prescribe pramipexol to depressive patients. But I went to a "private" neulologist(he is even a professor) where I paid 180 euro for an appointment. The doctor listend to me and was reviewing /googling “ pramipexol & anhedonic depression” in the web. He gave me a privat prescription , with that I could buy it in the pharmacy.
Normal doctors stick to national guidelines because of security issues, they can be somehow sued when a patient get worse or whatever, and lost their right to get paid from public health insurance. This is what I found out for Germany.
In another youtube viedeo someone sad that you can by pramipexol in mexico without prescription. I don’t think that its good to take medication without a doc. But maybe you find a doc who accompanies you.
Where are you from?
Good luck for you!
Maybe try ect if youve got money
Hello, very interesting video, especially on how the role of dopamine is neglected in large parts of psychiatry even though many symptoms of severe/melancholic depression stems from dopamine dysfunction (eg. anhedonia, cognitive impairment, psychomotor retardation etc). It's also interesting to note how medicines for Parkinsons (not just Pramipexole but also selegeline etc) also have utility in treating depression. Vice versa with the antidepressant tranylcypromine having good effects for Parkinsons (both selegeline and tranylcypromine are in a similar class of medications). Talking about tranylcypromine and selegeline, I wonder what you think of Monoamine oxidase inhibitors (MAOIs). They are (I think) one of the few antidepressants that as an entire class robustly boosts dopamine due to their mechanism of action (inhibiting monoamine oxidase which in turn boosts dopamine, serotonin, norepinephrine etc). I have heard a lot of anecdotal evidence on those using tranylcypromine saying that it has helped enormously with their anhedonia, which makes sense due to its robust dopamine boosting effects. There is a lot of reluctance out there regarding its use (eg. tyramine pressor effects, drug/drug interactions etc), but I also sense a kind of renaissance in interest of these drugs, largely spearheaded by Dr Ken Gillman and his website/publications on them. Probably that renaissance in interest also comes from people trying all the "newer" antidepressants that are largely serotonergic (eg. SSRI/SNRI) but still not getting adequate relief from their illness, and so they turn to MAOIs for remission. Anyway I am interested if you have any thoughts/ideas etc on MAOIs, thanks a bunch again for a very interesting video.
wow that was such an awesome, thorough and thoughtful comment about dopamine and MAOIs. I pretty much agree with everything you have said. I a actually emailed Dr Gillman in late 2019 or early 2020, and we were going to have a skype call to discuss MAOIs (I was early in residency training and didn't have any luck finding an attending/supervising psychiatrist that was interested in prescribing them), but then COVID happened and I was at "gound zero" (was training in Seattle) and it never happened. I would really love to have him on the channel to discuss MAOIS, I love his quirky but awesome, thorough website.
Your comment has inspired me to think about contacting him again to see if he would be willing to accept an interview on my channel. He is such a rare gem, one of the only doctors that I know of that promote and educate the masses about MAOIs that I am aware of.
I have always been interested in MAOIs, I think they often work when nothing else has (according the studies I've seen on treatment-resistant and melancholic depression). And agree that meds that are more heavy on MAOI-B inhibition might be an very good option for some people's anhedonic depression symptoms.
I've seriously considered trying an MAOI now that I am out of training (since last summer) but its hard to find a patient that it is appropriate for, at least for the patient demographic I serve in a rural area. Finding a patient that is willing to follow the strict diet, and finding a patient that is also willing to get off their SSRI/SNRI completely before starting it, AND finding a patient that is at low risk of an overdose attempt has been hard so far.
Thanks again for the great comment. I do want to come out with a slew of videos exploring MAOIs.
Hello, I also agree that in my personal experience dopamine is highly neclected in psychatry. Most of the doctors or therapists I ´ve seen didnt seem to understand or know the symptom anhedonia. I´ve been given Tranylcypromin in hospital last year. I also listend to the videos of Dr Gillman and apreciated them a lot. Unfortunately I couldnt get to the therapeutic dose of 20mg, because from 15 mg onwards I became very sleepy and weak. But i know people who did good on tranylcipromin. I might try Nardil later. Now I´m giving Pramipexol a chance to work.
thanks for your informative comment!
@@OllertonMD
After years of trying various antidepressants, it was finally methylphenidate that helped practically straight away.
It was clear to me 20 years ago that dopamine plays a huge role but is simply ignored.
@@paradoxeintervention5390 its crazy to me. Psychiatry has known for 70+ years that dopamine is vital to mental health, and yet doctors put patients on an endless merry-go-round of serotinergic antidepressants for patients that clearly have a dopamine signalling deficiency (low dopamine causes more melancholic/neurovegetative symptoms like fatigue, apathy, anhedonia, dread with daily activities, emotional numbness). The problem is, is that if dopamine is an issue for a patient, boosting serotonin will WORSEN low dopamine signaling. It also bothers me that a majority of antidepressants don't substantially increase dopamine. Wellbutrin is the only commonly prescribed antidepressant that boost dopamine, but even that is questionable (rodent studies show it boost dopamine; in human trials, its dopamine effect seems not as substantial or clear). There is Emsam and nardil, but those can rarely be prescribed for various reasons. Thats why I am so happy to have stumbled upon pramipexole. Its not a controlled substance and potently increases dopamine signaling (doesn't actually increase dopamine, but sidesteps low dopamine by directly agonizing its receptors).
Hoping new antidepressants that target dopamine get released, but I'm not holding my breath.
@@OllertonMD what I also don't understand is how some psychiatrists prescribe antipsychotics (outside out of low dose aripiprazole and other smal exceptions etc) to treat depression, as their raison d'être is to decrease dopamine!
Thank you for giving so much attention to this topic and providing such interesting info. Where are you licensed to provide services/medication management? You seem genuinely interested in your profession.
thank you my friend! I am only currently licensed in the state of Montana, but I hope to add Wyoming soon too. And yes I genuinely love psychiatry because I love seeing people start loving their lives again when their mental health improves through meds, therapy and lifestlye change. Its the best feeling ever.
Hi Doctor, thanks for all the great info, this info gives hope to many who thought that they have exhausted all of their options. What are your thoughts on adding pramipexole to bupropion? Would this allow you to take lower doses of each due to synergy, or contraindicated? Thanks for your time!
ive mixed both of those multiple times with good success, although once patients are on pramipexole they usually dont even need to be on bupropion at all anymore
Well THAT'S good news! Thank you.
@@OllertonMD
I have a question that is bugging me. I do have anhedonia, also CPTSD, I've had anhedonia for 15 years, nothing tackles it. But I honestly feel, I have no idea if it's possible that my anhedonia has to do with serotonin. Is that even a thing? I have a strong drive to do stuff, I'm very active and motivated even though I'm mostly in a freeze state, it will not stop me from cleaning which I used to love. But now I still do it and I expect to be happy but then comes disappointment. No pleasure, just a chore... I'm doing EMDR and my therapist says I need more time but cmon, I seriously cannot live like that. It's horrid. I did go through about 50 meds, they did nothing except I felt like I did meth after most of them but my mood didn't improve. So I'm off meds for almost 2 years now, I feel much better off them than on them, I'm learning to regulate my emotions but I feel like feeling positive emotions after doing things I like (I do more: yoga, dance, walks in nature, caring for animals, spending time with my long time partner) would really help me get it all together. I have it all, besides a job and a degree but I will do that when I'm able. I think if I felt pleasure my life would be great... I don't remember how it is to feel nice, it's been so long and I was a child, all a blur honest... So... can it be a serotonin issue?
I'm sorry you struggle with trauma :(. Anhedonia isn't thought to be from a lack or serotonin, and increasing serotonin has the potential in many patients to worsen emotional numbness. Dopamine is thought to be a big player in anhedonia. Trauma and chronic stress/fight or flight is an extremely common cause of anhedonia, and for many traumatized patients, anhedonia will 1. not improve until their trauma and PTSD is thoroughly processed in therapy and 2. is often the very last symptom to go away. IE it can take months after PTSD is substantially healed for anhedonia to go away. Good luck my friend.
@@OllertonMD thank you for your response. So that it gonna take a while cause I've been doing EMDR for over a year and we're not even halfway there :-(
@@OllertonMD it really makes me feel better to know it will come though. Thank you.
@@leniwiec2401 keep in mind I of course can't guarantee anything and I am not your doctor. If someone's anhedonia is caused by trauma, and trauma is resolved, there is a very good chance the anhedonia will improve substantially over months. Someone with trauma could also have other causes of anhedonia that are unrelated though, like sleep apnea, brain inflammation, low vitamin D, fried D2 receptors from chronic drug or cannabis use, etc. I do hope your emotions spring back to life after your trauma journey ends though.
Also combo bupropion + low dose amisulpride give also instant relief. Amisulpride is an antipsychotic at normal dose (200-800mg/day) but conversely is dopaminergic at low dose (25-50mg) and the effect is immediate 😊
YES! Thank you for bringing awareness to amisulpride. I never was taught about it in my 8 years of medical training, but ive read the research on it and am considering prescribing it to some of my patients.
@@OllertonMD Unfortunately doctors seems to be programmed by factory to treat depression increasing only serotonin through SSRIs......I realized that there was some link with dopamine instead of serotonin when I tried for the first time amisulpride(I took Deniban 50mg per day). First line SSRIs, SNRI (venlafaxine) and NaSSA (mirtazapine) does not work at all for me. Mirtazapine was basically a sleeping pill while SSRI a chemical castration. Amisulpride gave me some motivation to do things and get out of the bed but does not improve my cognitive impairment and brain fog. I was switched to bupropion that at the start was a miracle drug! I was finally able to do things that had become a struggle for me before, i enjoyed hobbies again and was able to focus and multitask without feeling overwhelmed. I thought I was definitely out of that dark cloud that was above me for over 2 years and finally see the sunlight when unfortunately the effect started to fade out. Then doubled the dose and it seem to work but it's still not as effective as it was in the beginning. Now I'm on bupropion but sometimes when I felt anhedonic I take a 50mg amisulpride pill (it's an instant happiness pill) and it works in hours but i'm terrified that combo might suddenly stop working at all 😪.
@@OllertonMD Here all doctors seems to be programmed by factory to treat depression increasing only serotonin through SSRIs......I realized that there was some link with dopamine instead of serotonin when I tried for the first time Deniban 50mg (amisulpride) added as augmenting drug after the first line SSRIs, SNRI (venlafaxine) and NaSSA (mirtazapine) does not work at all for me. Mirtazapine was basically a sleeping pill while SSRIs a chemical castration. Amisulpride gave me some motivation to do things and get out of the bed but does not improve my cognitive impairment and brain fog. Furthermore the cronic use it's known to skyrocket prolactine that is not good for a young man...so I was switched to bupropion that at the start was a miracle drug! I was finally able to do things that had become a struggle for me before, i enjoyed hobbies again and was able to focus and multitask without feeling overwhelmed. I thought I was definitely out of that dark cloud that was above me for over 2 years and finally see the sunlight when unfortunately the effect started to fade out. Now doubled the dose and it seem to work but it's still not as effective as it was in the beginning. Now I'm on bupropion but when sometimes I feel anhedonic and letargic I take 50mg amisulpride which wipe out all that bad thoughts within hours....it works but i'm terrified that this combo might suddenly stop working at all 😪
@@OllertonMDHere all psychiatrists seems to be programmed by factory to treat depression increasing only serotonin through SSRIs....but I realized that there was some link on dopamine instead of serotonin when I tried for the first time Deniban (amisulpride 50mg) that was added as augmentation strategy because first line SSRIs, SNRI (venlafaxine) and NaSSA (mirtazapine) does not work at all for me. Mirtazapine was basically a sleeping pill while SSRIs a chemical castration drug. Amisulpride gave me some motivation to get out of the bed and do random things (like cleaning house) but does not improve my cognitive impairment and brain fog. Furthermore the cronic use is known to skyrocket prolactin that it's not good in a young man....so I was switched to bupropion that at the start was a miracle drug! I was finally able to do things that had become a struggle for me, enjoyed hobbies again and was able to focus and multitask without feeling overwhelmed when unfortunately the effect started to fade out. Now doubled the dose and it seems to work but it's still not effective as it was at the beginning and occasionaly I feel anhedonic and unmotivated. In that occasion I take my magic Deniban pill that wipes out within half an hour all that bad. It works but I'm terrified that this combo bupropion 300mg + amisulpride 50mg might suddenly stop working at all 😢
@@OllertonMD Here all psychiatrists seems to be programmed by factory to treat depression increasing serotonin through SSRIs....but I realized that there was some link on dopamine instead of serotonin when I tried for the first time Deniban (amisulpride 50mg) that was added as augmentation strategy because first line SSRIs, SNRI (venlafaxine) and NaSSA (mirtazapine) does not work at all for me. Mirtazapine was basically a sleeping pill while SSRIs a chemical castration drug. Amisulpride gave me some motivation to get out of the bed and do things but does not improve my cognitive impairment and brain fog. Furthermore the cronic use is known to skyrocket prolactin that it's not good in a young man....so I was switched to bupropion that at the start was a miracle drug! I was finally able to do things that had become a struggle for me, enjoyed hobbies again and was able to focus and multitask without feeling overwhelmed when unfortunately the effect faded out. Now doubled the dose and it seems to work but it's still not effective as it was at the beginning and occasionaly I feel anhedonic and letargic. In that occasion I take a 50mg amisulpride pill that wipes out within half an hour all that bad thoughts. It works but I'm terrified that this combo might suddenly stop working at all 😢
What do you think about levodopa it’s also working on Anhedonia?
There are just a few tiny studies that ask this question but so far it looks promising. I would be very, very surprised if levodopa did not improve anhedonia. It has been shown to reverse anhedonia in primates so far. Since L-dopa straight up becomes dopamine in the brain (would be more effective if combined with carbidopa), and low dopamine is a key to anhedonia, it would be very puzzling if it didn't work.
I've never tried levodopa or carbidopa/levodopa. in my patients with anhedonia, but its something I've considered. Most of my anhedonic patients respond to pramipexole so I haven't really had to go there yet.
I've tried Proza, Paxil, Lexapro, Zoloft, Abilify, Lamictal, as well as Wellbutrin and the XR form. Would I be able to possibly bring this up to my psych since the typical SSRIs just haven't been working for me? I usually just get ED and eat a lot on top of anhedonia.
When a doctor isn’t personally familiar with more obscure treatment options, it can help to show them that there is enough evidence from decent quality human trials for it to be a rational option to try even if it’s not the standard of care and even though it doesn’t have the same level of evidence of standard antidepressants. Here is a meta analysis you might want to print off and bring in to your appointments and it might increase the odds of them being willing to try it if you say something like “I understand this isn’t a common thing doctors to prescribe but my anhedonia hasn’t improved in any other meds and I am interested in trying something outside the box.” It might also increase your odds if you review the side effects and discuss them in the appointment them and explain that you understand the risks and side effects and are still willing to try. Ultimately there’s no way to know if any given doctor is going to be willing to try pramipexole for depression or anhedonia though, but I wish you the best of luck.
Here is a good study to look over and maybe even bring to your next appointment with your doctor:
onlinelibrary.wiley.com/doi/10.1111/acps.13055
If they seem hesitant you can also say “can you look into it and let me know later if it’s something you are willing to try for me?” Since most doctors (rightly so) will not feel great about prescribing a medication off label without being acquainted with the evidence, risks and benefits
@@OllertonMD Thanks a million for this, Dr. Ollerton!
Hey man what about levodopa? Isn’t that just artificial dopamine? Would this work?
Wow, I think most EVERYONE wishes YOU could be their Doctor! Ever think about internet subscriptions Doctor? Would be great. SOO many millions are suffering so bad with this. Very interesting and Thanks so much for discussing this extremely important subject.
thank you so much for the kind words. My dream has always been and continues to be to set up a virtual telepsych clinic and get a medical lisence in 30+ states so I can focus on helping people with anhedonia and treatment-resistant depression. I have a full-time job at a hospital right now but in the next 2-5 years that is the plan!
Hello, doc. I'm from Brazil, thanks for the awesome video and sorry for bad english. I was wondering if you could explain this phenomenon to me. I have had anhedonia for years and recently my psych tried pramipexole with me and we observed the following: Low doses (0.5-0.75mg) improve my sexual dysfunction, but when increasing the dose (2mg), the anhedonia worsens considerably. Why do you think this happens? Have you ever observed this reverse effect in any patient?
Fala Mauricio. Nao sou o medico do vídeo mas tenho estudado bastante a respeito para tentar superar a minha anedonia. O remedio que voce citou eh um agonista da dopamina. Ou seja, ele aumenta a dopamina circulante ali no cerebro. Acontece que quando voce aumenta a dopamina de forma exógena (que vem de fora) de forma relevante, o cerebro tenta ``equilbirar`` esse aumento subito aumentando a funcao das enzimas monoamina oxidase A e B, que vem e ``limpam o excesso`` de dopamina e outros neurotransmissores circulantes no cerebro. Agonistas de dopamina (remedios pra deficit de atencao, parkinson etc) funcionam apenas em doses baixas para aliviar a anhedonia, quando nao ativam as enzimas MAO e nao fazem downregulation de receptores. Como agonistas da dopamina fizeram isso contigo, tudo indica que algum remedio INIBIDOR das enzimas MAO possam resolver a sua anhedonia. Converse com seu medico a respeito de MAO-INHIBITORS
@@moacirbarbosacastro8923Boa noite, meu querido, obrigado por responder! O Parnate não funcionou contigo?
I had recently been on 4mg pramipexole and the side effects were too much for me. The doctor change me over to the 4.5mg Extended Release and all of my issues with the side effects went away almost immediately. The ER is much smoother it its release.
Very interesting! I've only done IR so far. Will consider ER more often. I tried once, but Medicaid refused it. I think I'll have better luck with trying to prescribe ER with patients that have commercial insurance. Medicaid will do anything to save a penny here or there.
@@OllertonMD I have commercial and they paid. The price difference is ridiculous. I think 30-days of IR is about $20 and the ER is $1,000. I tried breaking the IR into 4 doses, but I still ended up with 4 spikes.
With ER, it is like "did I remember to take it? " because it is that smooth.
@@scottvk4129 my goodness a thousand dollars?? the pharmaceutical industry is so messed up
I have been on the drug about 8 months now. I am now on 4.5mg of Extended Release and that has made a big difference in lowering the side effects of pramipexole. I would say that I am about 25-33% better since starting prami. I haven't felt any real improvements in many weeks now, however, I also have not had any downturns or relapses. It seems that I have entered a maintenance phase and I am not sure that I will see any more positive surges. it was at the 3-4mg doses before I noticed any positive changes, smaller doses had little to no effect for me.
@@scottvk4129 I also experienced fewer side effects (mostly less sleepiness and less intense sleep attacks) after switching to extended release. Do you just take it once a day?
Dr. Ollerton: does it matter whether we use the immediate release or ER for depression?
thats an interesting question. All of the studies I've seen has used instant release as far as I know. I've always used instant release with good effect with my patients. ER could be a possibility to mitigate side effects though, like if someone has nausea on it or something
Have you ever looked at what Chris Palmer a doctor in Boston is talking about a low carb or ketogenic diet to restore energy homeostasis in long covid. Bipolar and schizophrenia on occasion. Wonder if you have ever considered using taVNS in your patients with anhedonia or Avolition issues. Parnate as well, maybe in combination with a low carb lifestyle. There certainly are desperately needed drugs for anhedonia conditions which are rare but devastating, also looking at the work of Dr. Diego Pizzagalli at Mcclean studying it in relation to the CMS model
How tf did you know about the white noise music thing? That is, in fact, a Thing? I went all around my house trying to find the faint 'radio' that was always playing in the next room, playing fake yet familiar music until I turned off all the air purifiers. What in the sweet Psychosis is that?
its my job to know about weird and unusual side effects :) it is indeed a thing. when psychotic symptoms are very mild, it tends to be more about your brain misinterpreting real sounds than sounds entirely made up by your brain, which happens when psychosis becomes more severe
I really like this channel.
thank you my man!
I have Schizoaffective disorder and I’m currently on 40mg of Latuda. I used to hear voices of neighbors or other people talking poorly about me. I also have compulsive behavior like drug abuse
I’m 45 days clean from Nicotine, Kratom and Xanax (tapered with Valium). Everyday has been a struggled. My Prozac no longer works and my libido is ruined permanently
I currently have severe anhedonia and nothing works. I have constant urges to drink and do drugs and I risk relapse everyday.
Would Pramipexole work for me or should I try something else? I literally can’t enjoy anything in life and I feel dead inside
Edit- I also was prescribed 5mg of Abilify and I got severe akathisia
did the anhedonia start after you started tapering off, or stopped, nicotine, benzos and kratom? all of these can and usually will have anhedonia as a post acute withdrawal symptom, which can last for months
@@OllertonMD My doctor told me it was likely protracted withdrawal from Kratom. I was taking heavy amounts of extracts and had to quit CT because of tremors and psychosis. The withdrawals were very severe and I didn’t sleep for a week. I still crave Kratom to this day
After 30 days, my sleep went back to normal; but on day 42, I relapsed and had another Kratom extract. My sleep has been shit again for the last few nights; however, I didn’t feel other physical withdrawals unlike the first time I quit
My doctor recommended that he rises the Latuda dose
What's your take on suggesting this medication for someone trying to recover from long-term stimulant use and facing immediate anhedonia post-cessation? Typically, SSRIs are recommended, but they've proven ineffective in the past.
I would personally never prescribe an SSRI to someone that is suffering from stimulant PAWS anhedonia, given boosting serotonin will reduce dopamine long-term. I would venture to guess pramipexole would be effective for anhedonia from chronic stimulant use.
I took thioxanthene last year due to a wrong treatment, and since then, I have been suffering from Anhedonia. In this situation, can I take Pramipexole to activate my dopamine receptors?
another great video!!
Sprawdzić status paczki?
Hello Andy, thank you for your comment
So, basically any type of pain meds that elevate dopamin should help? Codeine, vicodine, tramadol etc?
probably but treating anhedonia with opioids is a dreadfully dangerous idea on multiple levels and do not recommend it
Tramadol worked miraculously for my anhedonia for about a year, but the late term side effects were too much to bear..Now I'm 4 months off and the anhedonia is worst then ever, like it just destroyed my dopamine receptors permanently..very discouraged.
@@michaelsteven1090 the only drug I know of that has been shown to permanently destroy dopamine centers in the brain is cocaine and meth. you might recover if you stay off of things that hammer dopamine receptors for long enough. Keep in mind that poor sleep, depression, and PTSD are main causes of anhedonia as well, and if someone hasn't addressed those, there is a good chance anhedonia will continue
@@OllertonMD Thanks doc..at 64, I've unfortunately learned that all the good, working receptors I had are gone..Maybe from "above avg" abuse and age..I think its the combo..Nothing prescribed or even recreational helps like it did, just for some relief..Am I right about aging receptors not working like they use to?
@@michaelsteven1090 i cant really comment on your specific situation since you aren't my patient, but in general, it can take months, maybe years of abstinence from hard drugs or cannabis, for dopamine receptors to get back to some sort of baseline. People's anhedonia usually improves substantially after *protracted* abstinence. The only drug I know of that appear to potentially permanently damage dopamine signaling is cocaine and methamphetamine.
thank you for your video, very informative is it possible to consult you in PM I am going through severe anhedonia, before going on a possible treatment
currently taking Mirapex 0.375mg ED, "feel" nothing besides tiredness, undless boredom and slight apathy / maybe increase in anhedonia.
any insights?
maybe this dose is too high and is decreasing dopamine?
first off, pramipexole can cause sedation, which is why it is usually prescribed at night, but even then, some patients have next day sedation. for some people, it just wont be tolerable/won't be a good fit for their brain/body.
Secondly, if I am trying to treat anhedonia, 0.375 is way too low. I start people at 0.5 mg and increase by 0.5 mg every 2-4 weeks until we get to 2-3 mg nightly. The studies that use pramipexole for treatment resistant depression use dosages of 2 mg, one study used all the way up to 5 mg! I've never ventured that high though. The highest I've needed to go is 3 mg.
@@OllertonMDthank you for your elaborate response. I once tried a double dose of 0.375 and I felt very out of place, agitated etc.
maybe this drug is not suitable for me.
Also caffeine, amphetamines, modafinil and other stimulants make me sleepy or tired.
Pramipexol was my last resort to resolve anhedonia.
Hello doctor, can you counteract the compulsive behaviour of pramipexole?
a patient that has compulsions on pramipexole can do common-sense things like change their environment and habits, but if the compulsions are serious or potentially will cause catastrophic outcomes (like a recovered gambling addict that starts getting urges to gamble again and could destroy his or her life savings) then it is usually discontinued
Hello Dr. Hope you're well. Do you have any recommendations I may speak to my own personal psych. about regarding anhedonia and cognitive dysfunction? I am literally learning disabled now as compared to my previous self. Not tooting my own horn believe me but I was an outstanding engineering student now my cognitive state is so terrible I simply cannot remember things that happened mere minutes ago. Do you have an recommendations regarding medications for anhedonia and severe cognitive dysfunction I may bring up with my psych? Thank you. Greetings from Canada.
from my experience of being prescribed pramipexole for restless legs syndrome, is after a couple years, you will likely develop a movement disorder. But in the meantime, you likely will feel "happy", for about a year. Then when you get off, you're worse than when you stated. That was my experience anyway. A hight animal fat diet, and weight training has helped a lot. I have anhedonia right now, and it's been 2 years since stopping the prami.
Can you please help me. I'm trying to figure out anhedonia on my own. I read on Wikipedia that pramipexole is, on the one hand, D3 receptor agonists, on the other hand, it increases dopamine in the prefrontal cortex. Which of the two things do you think helps anhedonia?
I ask because I used to take latuda (lurazidone) and in low doses it relieved my depression and anhedonia. Lurazidone is an antagonist of D2 receptors, but it is an agonist of 5 ht1a receptors and therefore increases dopamine in the prefrontal cortex, as well as pramipexole.
broadly stimulating D2 or D3 receptors, or increasing dopamine in the prefrontal cortex, vital for depression and mood and positive emotion, will all have the potential to improve anhedonia. Another option i use antipsychotic-wise is low-dose abilify, which generally increases dopamine at low doses (ie 2.5-5 mg) and starts blocking it at higher dosages given its dopamine partial agonist properties.
Why not cabergoline? Compounding pharmacies can make low dose 50 to 125mcg capsules. (Or lower if needed)
Cabergoline stimulates D2 receptors more as well.
honestly that would probably work, but has essentially no human trial evidence, thus pramipexole would be a more rational approach (from a doctors perspective since we try to stay within treatments that have at least a decent amount of evidence from RTCs). I just reviewed the literature on cabergoline and mood for humans in the past year, it might have been right around the time I made this video actually, and remembered being dissapointed that there hasn't been much research on it for mood in humans, if at all. In rodents it improved depressive-like symptoms and increased BDNF, so definitely lots of potential.
@@OllertonMD I have no libido despite TRT being optimized. I have autoimmune disease and immune system lower than it should be, so targeting dopamine receptors directly should work. I remember taking Cabergoline about 6 years ago and it did increase libido. However, it stopped working and I was getting side effects (I don't remember what though) I believe I tanked my prolactin level to zero. Prolactin has immune system benefits, so we want it at least in range. This time around I'm going to micro dose the Cabergoline to hopefully restore my libido and prevent side effects. I originally did 0.25mg twice per week, so that was way too much for someone without Hyperprolactinemia.
I have been experiencing this for years, like for a few months at a time. I see my doctor in 2 days and this is something I’m sure that she will be willing to try!
i hope you and your doctor are able to find something that works for you , whether that be pramipexole or something else. out of curiosity, do the months of anhedonia occur mostly during the fall/winter months, or does it seem random?
@@OllertonMD it is actually quite random. I have used a sun therapy light for years, maybe that's why it isn't more prominent in the winter. After looking into the medications, I know I'm not a candidate for them as I am currently experiencing kidney issues. I do appreciate you sharing this information
Love your channel, wish more Drs were interested in these topics.
You mentioned you try Wellbutrin and low dose Abilify first. Do you ever combine the two? If so, are there any considerations for dose or side effects when combined?
I'm taking 300mg Wellbutrin, 10mg Adderall, and low dose Testosterone HRT(born female, transitioning) atm and my Dr wants to add Abilify. I'm scared of taking too many meds together bc adding an SSRI and SNRI may have caused emotional blunting, which is persisting as anhedonia after stopping :(
I'm also hesitant bc I found out a week ago I have very low vitamin D. I'm curious to give supplementing a couple months before more meds. but I'm not a Dr and Abilify may be safer than I'm assuming
thank you!
I do combine wellbutrin and abilify frequently. I use smaller dosages of abilify when combining with wellbutrin though, as they both interact in the liver through a liver enzyme called CYP 2D6 and this can make abilify levels be higher than expected in the patient's blood, which will increase the risk of any potential side effect of abilify. So If I have 150 to 300 mg wellbutrin onboard, I make decide to use 2.5 mg abilify instead of 5 mg.
Low vitamin D is very, very common if you live in a place/state in the US that is on the northern end of the country. Low vitamin D has historically contributed to my patient's apathy, fatigue, and anhedonia. I'm always a little surprised at how better patients feel when they get their vitamin D levels corrected.
Personally, if I have a patient who's vitamin D is around 20 or lower, I'll prescribe them 50,000 units of vitamin D2 once or twice weekly for 4-8 weeks. This allows the vitamin D to corrected within weeks instead of the months and months it can take by taking 1-2k a day.
Good luck my friend!
Regarding your low Vitamin D levels- I've been treated with a myriad of modalities for treatment resistant depression in Bipolar 2 for MANY years. I'm not a supplement/vitamin user at all, but did start D3 when I learned it was really low. Nothing has had a more positive effect for me than correcting this! Just wanted to pass this along as I thought it might be helpful. Best of luck to you!
@@wot4me2 Thats awesome!!!! I plan on making a video about vitamin D and depressive symptoms. I have had quite a few patients come in and I test their vitamin D and its low, often under 15, sometimes single digits, and I usually prescribe 50k units twice weekly for 2 months and some patients come back and say they have regained their energy and interest in doing things. Low vitamin D is super, duper common.
@@OllertonMD Thanks SO much for your comment, Dr. Ollerton! Low D is incredibly common; I wish everyone struggling with low mood would test it automatically- what can it hurt? : ) Looking forward to your video on the topic, and thanks again!!
@@OllertonMD thank you! that's helpful to know regarding the abilify and vit D dosing.
I've started taking vit D and right away my sleeps a lot better. also noticed music is more enjoyable again. will keep up behavioral activation but I'm hopeful to see positive changes in a couple months
I suffer from "PSSD" after changing medication from Mirtazapin to Quetiapin, Agomelatin and Methylphenidat. Now after 3 month I take Mirtazapin again but it's not like before...i still suffer from erectile dysfunction but I'm not sure what's caused by the after effects of the change of medication and what's caused by anxiaty/depression (I think it's a combination). I'm afraid of trying other antidepressants, especially SSRI. I was thinking about to try maybe Ropinirol or Pramipexole cause they are discussed to may being a treatment of PSSD...
Do you have any experience with the off-label use of Ropinirol/Pramipexole? My psychiatrist suggested Wellbutrin...I've tried it 3 times but I can not tolerate the side effects so this don't to seem an option...
(Thanks and sorry for my bad english!)
I'm sorry you have suffered from this. I usually use wellbutrin for sexual dysfunction caused by SSRIs , but usually only when they are still currently on an SSRI. PSSD is rare enough that I haven't seen it yet in person. PSSD is a seriously under-researched problem so there are no evidence-based treatments for it. I have heard patients tell me that pramipexole does increase sexual drive and overall sexual health but haven't used it for sexual problems yet. I have seen or heard hypersexuality on pramipexole though, so sometimes the effects can be "over the top."
How does it compare to cabergoline? I tried cabergoline previously and I didn’t think it did anything much. Is there something particularly special about pramipexole for anhedonia, because, on paper, they look identical in how they work.
@@bobbypukes605 yeah they are both dopamine receptor agonists, I assume they would feel similar , but can’t say for sure since I’ve never prescribed cabergoline before since it is usually used for prolactinomas which I don’t treat as a psychiatrist.
I thought that the dopamine agonists aren’t used much in RLS due to the profound risk of augmentation of symptoms.
Do you see anything akin to that with your anhedonic patients?
i have read some studies suggesting dopamine agonists can worsen RLS over years, probably due to repector tolerance. This hasn't happened with any of my anhedonic patients on it, but then again, I've only been prescribing it for a little under a year and a half. Its something I am always monitoring for though. thanks for the thoughtful comment. Tolerance is a significant risk of many psych meds. Especially SSRIs. I see those poop out on people fairly frequently.
The music at the beginning and end of this video gets stuck in my head, but it is a good stick because I find it calming. Can I find it somewhere? Thank you
haha thank you. that is high praise because I composed and recorded it myself in my studio :) I don't have it posted anywhere besides these videos on youtube
@@OllertonMD How cool is that? Guess I will keep watching and listening and then hum the melody the rest of the day. I do really like it. Thank you for creating the music and these videos
@@carojhig99 I was in a band in college called The May Reunion. If you want to check out my music, its on all the streaming platforms (last time I checked haha...we haven't been active in the band in a decade). The song "Blueberry" is one of the songs I'm most proud of. I am also proud of "Mountain." I was the singer, guitarist, and wrote all of the songs, usually with the help of my buddy and keyboardist Andy.
edit: its still up! here is a link to spotify:
open.spotify.com/album/6XkVc7c5Xkj8ZfltoYri7V?si=r5328DheTjmVdmCqLRm6Sg
@@OllertonMD Thank you, that is awesome! I'll check it out.
Thank you so much for the link! Today was a perfect rainy day to listen to these songs. Blueberry and Mountain = beautiful. I have other favorites too. Music is so important and I love knowing of these songs.
I want to ask my doctor about this, but I’m nervous the answer will be no. I also am fairly certain I have restless leg syndrome (or is it just restlessness from depression/anxiety?) however, I do have adhd and she recommended taking Concerta for the Anhedonia. It helps me stay a little more focused, but I still don’t have enjoyment or pleasure. Do I even bother with trying Wellbutrin? Would I be good candidate for pramixepole?
I cant tell you which meds would be appropriate specifically for you, but I am always a fan of minimizing meds; I would personally tend to treat someone with anhedonia and RLS with pramipexole as it would help both.
I have decent luck with wellbutrin for anhedonic depression, but not nearly as much success compared to pramipexole. I have yet to find a med for anhedonic depressive symptoms that works better than pramipexole.
Thank you for your response!
How does this med relate to MAOIs, specifically Parnate? I was on a very high dose for 1.5 yrs and it helped a tad for a period of time & I got off because of side effects and no longer a benefit..
I’ve suffered from this all my life. It’s nice to know there may be a medical way out. I’ve had 3 ssri and they all made me feel numb to the point where I prefer my anxiety.
@@stefgreen5237 yeah tbh I’m not a huge fan of SSRI and rarely prescribe them for people that already feel flat emotionally as SSRIs appear to flatten moods, regardless of if the emotions are positive or negative
Hi I have something that I think you may find interesting or have some thoughts on.. so I’ve had anhedonia and broader emotional numbing for years now & something that reliably makes a big impact against it is clonazepam. It’s obviously not a great solution but I’m wondering if you could comment any thoughts as maybe to why it has such an effect? I can’t imagine its it’s anxiolytic property because when I’m not remotely anxious it still has the effect. Could this also be affecting the ventral tegmental pathway? Thanks in advance
That’s almost certainly from benzodiazepines ability to reliably increase dopamine signaling in the reward circuits like the VTA/ nucleus accumbens. Any drug that has reinforcing properties like benzodiazepines and opioids can boost dopamine. Benzodiazepines will cause rapid tolerance and a hellish withdrawal syndrome and can exacerbate anhedonia once tolerance or withdrawal sets in
Can the pramilexole promote healing of the dopamine system or does pramipexole need to be taken forever? I have tested this already and it does work but the next day I’m a zombie.
I wouldn't count on pramipexole doing anything positive for dopamine receptors long after you stop taking it. There is some interesting research showing pramipexole causing neurogenesis in a few small areas of the brain like the olfactory bulb (smell) and hippocampus but I don't think it will upregulate dopamine receptors long term. In fact, stimulating any monoamine receptor with a drug can downregulate them with long-term or excessive use. This is why its never a good idea to suddenly stop lots of psych meds-you need to give your brain time to upregulate any receptors that have downregulated during drug therapy
Cozy music. Informative. Needed. Reminds me of visiting dr.maruki in persona 5 royal
After coming off of antidepressants how long does it take for anhedonic to go away
if anhedonia is caused by an antidepressant, it should generally disappear within a few weeks. For short or intermediate acting meds like paxil, effexor, zoloft, lexapro, celexa, I would venture to guess a week or so. If its from prozac, which is very long acting, it could be closer to a month since fluoxetine and metabolites like norfluoxetine are extensively metabolized by the liver and take about 30 days to be essentially our of your bloodstream.
Some patients (none that I have had personally, but I've read plenty of stories online) believe they have long-lasting effects from antidepressants that cause numbness far after it is stopped, like PSSD. If this truly exists (I personally think it does, albeit very rarely), many people who believe they have PSSD not only suffer from longer lasting sexual numbness, but they often report emotional numbness as well, and important but neglected feature of PSSD.Out of the thousands of patients I've spoken to that have been exposed to antidepressants, none have reported long-lasting sexual or emotional numbness to me months or years after stopping the med, but that doesn't mean this rare phenomenon doesn't exist.
One type of med that can definitely cause emotional numbness and anhedonia months after getting it are LAI antipsychotics (long acting injectibles) since these dissolve slowly under the skin into the bloodstream for 1 to 6 months after the injection. For this type of side effect from this class of meds, there isn't much that can be done unless a med is administered that binds to and aognizes dopamine receptors more intensly than the antipsychotic is able to bind and block them. This is one of the many good reasons to have a patient trial the oral formulation of the med for a few months before considering an LAI because once its in your body, thres no getting it out except by having it run its course.
Have you ever prescribed ropinirole (Requip) for anhedonia?
I've tried it as it was more affordable and it worked faster for me (3 days) than pramipexole (5-7 days) but unfortunately it lowered my blood pressure too much even in low doses and when lying down. There was also a lot more drowsiness and sedation.
I learned that it affects the sigma receptor in addition to the D2 and D3 receptors and drugs which affect the sigma receptor can cause more rapid relief of depressive symptoms.
I have yet to try Requip for patients, simply because pramipexole has better evidence for depressive symptoms. I appreciate you bringing up sigma receptors. This is a very neglected topic in psychiatry and plan on coming out with a video about it soon!
Can you please list some of the studies please? Thank you. My psychiatrist mentioned trying pramipexole but mentioned the possibility of compulsive behaviour.
heres a brand new meta analysis for unipolar and bipolar depression that I haven't had time to read in full yet, might be worth checking out:
www.ncbi.nlm.nih.gov/pmc/articles/PMC10141126/
One notable thing I have read in this study glancing over it is that it appears compulsive behavior might be more of a risk for patients with Parkinson's disease than those with mood issues, which is good news! I've had a few patients that did have an uptick in desires to gamble and shop, but it hasn't gotten out of control for any of my patients on it yet. No idea why parkinson's patients would be more likely to experience compulsions than mood patients, but it might be that these PD patients might already be on other dopamine meds like sinemet or seleginine already
The only pramipexole study I'm personally aware of that specifically addresses if it helped anhedonia was not published yet at the time. I straight up just emailed the guy in charge of the study and he said they did find it helped anhedonia.
Do you know of any natural ways to boost dopamine receptor activity?
I am not aware of natural dopamine *receptor agonists* (molecules that aren’t dopamine but nevertheless bind to and stimulate dopamine receptors) but there are various natural supplements that increase dopamine signaling in some way. The most straight forward of which would be straight up L-dopa, the direct precursor to dopamine , which is found in Macuna Pruriens. There is apparently enough L dopa in this supplement/food (it’s a type of bean) that a few studies show it might improve Parkinson’s disease.
Cold plunges
Got prescribed this for RLS and got up to 1 mg. It made me have muscle weakness (I'm in my early 30s, man!), serious anhedonia, sleep attacks, insomnia, and other adverse symptoms. The augmentation was not fun. I even tapered down gradually to discontinue and got to less than .125 mg and still got dopamine agonist withdrawal syndrome. I was taking it with Parnate and was getting crying spells and brain zaps which I resolved with temporary dose reduction. Case in point, if you get an Rx, be aware of the risks, and keep your expectations realistic.
thank you for your comment. I agree, there are risks to every medication. Parnate + pramipexole sounds like a very powerful punch. I can see why this could be intolerable for some people.
The problem is, how am I supposed to get my doctor to prescribe me that high dosage on pramipexole if I she dont even know anything about anhedonia?
is she a psychiatrist? if not, you might have better luck with a psychiatrist. If she is a psychiatrist, then that is just sad. Its sad to me how little even psychiatrists know or care about anhedonia, a pervasive, life-destroying symptom that often lingers even when other depressive symptoms go away with classic treatment options.
You can also send her or print off this meta analysis to show her that it might be a reasonable option to try out.
www.ncbi.nlm.nih.gov/pmc/articles/PMC10141126/
Hi doctor. Started pramipexole (augmenting with escitalopram) for treatment resistant depression or PSSD (not sure which exactly but I suffer from low libido and the cognitive symptoms i.e. emotional numbness, anhedonia, slow processing, etc). I started at a low dose 0.125mg and went up .25mg every 5 days, started experiencing more emotional numbness as I went 1.25mg onwards. Currently at 2.75mg, should I reach for the target dose 3mg or go low? And if u recommend going low, should the taper be at the same rate I went up or can it be lowered faster i.e. .5mg every 3 days or so?
Update?
update?
Thank you for this information. Buproprion was the best anti depressant I was every prescribed all the way back in 2006-2008, but sadly after two years I took a grand mal seizure and had to stop taking this medication. Pramipexole has piqued my interest, I just don't want to risk another seizure - would this be an unlikely side effect?
I've looked into the risk of seizure from pramipexole and haven't found anything yet to make me believe seizure is a risk of pramipexole. I've successfully prescribed it to a patient that had severe, treatment-resistant epilespy and this patient never had a seizure on it
@@OllertonMD thank you so much for this information, I am ready to give it a try. :)
Have you had any patients experience dopamine agonist withdrawal syndrome (DAWS) upon discontinuation of the medication? How big of a risk is this?
Impossible to say as I have only been prescribing it a year. I did have a patient or two that got up to 1.5 mg stop taking it without issue but they had only been on it for months.
If you are on a high dose dopamine agonist for months or years and suddenly stop, I can almost guarantee most people will experience a withdrawal syndrome for at least 3-5 days. Fatigue, restlessness, sweats, probably anhedonia as well.
@@OllertonMD Oh okay, that makes sense.
I have read some studies (admittedly I am not qualified to interpret them), where the patients experienced a protracted withdrawal (they may have been Parkinson's patients too). In some cases, it never went away until they went back on pramipexole.
This concern is commonly expressed in various subreddits among people considering taking pramipexole for depression or anhedonia, so it could be worth addressing in another video at some point. It seems to me that many decide not to take it out of fear of "augmenting" their dopamine system in some negative and permanent way.
@@codeman55555 excellent points. I would love to make a video on DAWS.
Do you by chance remember any articles you came across showing DAWS being protracted, or having PAWS-like qualities? I' havent come across any articles like that yet but would love to read them.
Hello, thank you so much for this video! I consulted with my psychiatrist, and he said that Parkinson's drugs are addictive. What is your opinion on this?
seems like the psychiatrist one of those guys who is like all drugs are bad just take the ssri goddammit
there is no known abuse or addiction potential to pramipexole that I am aware of. He might have been referring to the fact that dopamine agonists can make people compulsive with things like sex, spending money, gambling, etc.
They are physically addictive in the sense that they cause withdrawal symptoms if abruptly stopped.
Can I take Ropinirole instead of Pramipexole for Anhedonia??
the evidence is pretty scant on ropinorole compared to pramipexole. The most recent study I know of for ropinorole vs placebo for depression actually showed no difference between the two
@@OllertonMD Well that's surprising! Are they both not dopamine agonists?
Hey Doc,
What do you know about the phenomenon linked with pramipexole known as augmentation (worsening of symptoms from baseline), specially in regards to restless leg syndrome I believe. A lot of people on RLS forums hate this medication and say it shouldn't be taken long term or at all. I sometimes get RLS if I take an antihistamine or some SSRI's so I'm just worried that if I start prami, somewhere down the line its gonna hit me with a worsening of RLS.
Cheers
I’ve never heard the term “augmentation” used in that way. Augmentation in medicine means to add a new treatment to an existing one, ie like augmenting sertralinr with Wellbutrin.
Maybe the forums are taking about how restless legs can worsen if you taper off of it too quickly after prolonged use? That is definitely a thing. This is true of most psych meds, ie having the risk of some sort of withdrawal syndrome if stopped too abruptly. I’ve never heard a patient tell me pramioexole itself worsened their RLS though. Antihistamines definitely worsen it for most people though, especially Benadryl which is an evil drug altogether haha
Augmentation is a common problem with all dopamine medications in restless legs. The same goes for pramipexol. Keep the dosage as low as possible and when it stops working, switch to rotigotin patch and if that fails too, switch to opioids....
If you’ve never heard of augmentation with Mirapex, I question your legitimacy and psychiatry.
I’ve been on it for 20 years and I’m trying to tape back and it’s miserable. According to what I’ve read, it’s not the first line treatment for RLS any longer because of the severe side effects, the biggest being impulse control disorders.
Anyone reading this, please do research beyond this video.
Ive tried pretty much every dopamine agonist and nothing has helped. Leads me to believe that there are more systems playing a role in anhedonia. Some research has stated the endocannabinoid and opioid systems may be involved
I feel quite confident opioid signaling is involved in hedonic tone; anyone that has been prescribed an opioid knows it boosts positive emotions. However, there are a litany of problems using mu opioid agonists for mood issues, such as tolerance, addiction potential, and the inevitable withdrawal syndrome that will occur trying to stop it.
I personally believe kappa signaling is related to anhedonia and dysphoria. I am hoping there will be studies on kappa agonists for mood and anhedonia.
@@OllertonMD Thanks for the response. I really do hope some sort of fix is found In the future because it is an incredibly empty existence to not have emotions.
@@CheeseKransky12 hold in there friend. I have many patients who felt nothing for a long time and then and emotions started coming back. Its difficult because there are so many reasons someone can become anhedonic. Sleep disorders, brain inflammation, low vitamin D, poorly treated depression or PTSD...by far the most common cause I see is chronic anxiety. I think the brain shuts down the emotional processing regions of the brain to protect from the toxic effects of being fully exposed to anxiety or unresolved trauma. Just like dissociation is the brain's way of trying to disconnect one's consciousness from the full weight of severe anxiety or trauma, I think anhedonia is sort of a milder version of this protective mechanism.
@@OllertonMDI imagine its chronic anxiety and unresolved trauma in my case. Maybe something will shift in the future
@@CheeseKransky12 I'm sorry to hear about your anxiety and trauma. I don't know if you have PTSD or not, doesn't really matter, trauma is trauma and can manifest in different ways. Trauma very often requires a full course of some sort of exposure therapy, like EMDR or tf-CBT. Something to consider with your healthcare provider(s). I've seen my patient's lives absolutely transformed by trauma-focused therapy. Good luck my friend.
Hello sir. What are your thoughts on combining this drug with venlafaxine for long term treatment resistant depression, anxiety, anhedonia and suicidality?
I was interested in trying an MAOI after trying ~8 SSRI or SNRI meds but MAOI are not available in my country.
Right now my plan is to experiment with higher doses of Venlafaxine and potentially try Lithium augmentation.
Any hypothetical thoughts on augmenting Venlafaxine with Lithium or Pramipexole?
Thanks
combining venflafaxine with pramipexole is something I would certainly consider in some of my patients. When you bump venlafaxine high enough, ie 250-30 mg, it actually becomes a SNDRI, ie it starts also effecting dopamine at higher dosages. Adding pramipexole would then increase dopamine, which often relieves anhedonia, from two separate angles: the high dose venlafaxine would block the reuptake of dopamine at the synaptic cleft, and pramipexole would directly stimulate dopamine receptors.
Another somewhat popular combo with venlafaxine is adding mirtazapine. Venlafaxine + mirtazapine is referred to as "California Rocket Fuel" by some psychiatrist. There are a few small studies showing its a good option for treatment resistant depression- assuming the person can tolerate mirtazapine's sedating effects that is
good luck my friend.
@@OllertonMD ah yes, I used to take mirtazapine as well for years. Thanks for the information ! Much appreciated 🙌
Thanks Doctor Ollerton. Generally speaking, can Pramipexole be added to MAOIs?
as far as I know there is no absolute contraindication, and in Parkinson's disease, pramipexole and seleginine are sometimes combined
Thank you doctor!!! @@OllertonMD
@@joekeen117 my pleasure. if you are looking to start an MAOI, I wish you luck finding a psychiatrist willing to prescribe one. It is very hard.
I have abilify and it's 2mgs my Dr prescribed to me for add on to Prozac for OCD and I've been scared to ever take it , been saving the scripts for 6 months and just don't want to be on an antipsychotic medication but seeing that it can help dopamine makes me curious to try it
be warned that LOW DOSE abilify can INCREASE dopamine signaling, which for many people with OCD, will worsen their symptoms. It is generally thought that BLOCKING dopamine signaling is the key to antipsychotics efficacy in OCD. Abilify for most people probably won't start blocking dopamine receptors until they get past the 5 to 10 mg range. Risperidone and seroquel have better evidence in OCD than abilify. you should always feel free talk to your doctor about your concerns and I hope you and your doctor can get your symptoms to a more comfortable place. OCD can be the worst!
What if you have Major Deression and OCD?
@@user-sf3qr6jt9j I have OCD and the pramipexole made me more impulsive because it increases dopamine in a different way. Definitely not something to take for OCD. Hope your OCD gets better for you
@@user-sf3qr6jt9j doctors will usually treat both with high-dose SSRI. Unusually high dosages of SSRIs don't usually improve response rates for depression, but high to very high dosages (ie 100+ mg fluoxetine, 300+ mg sertraline) are often vital to get a handle on OCD. Meds like pramipexole will potentially worsen OCD for a significant percentage people, although this is theoretical and hasn't been actually tested.
Great question btw!
PS/random thought: for those that don't tolerate high dose SSRI, I often consider NAC, a supplement that appears to improve OCD in various studies. NAC is nice because besides smelling/tasting nasty, tends to have little to no side effects for many patients
You seem like a nice guy.
Hello. Thank you so much for the video. Can you explain why it's worth trying pramipexole first, and not MAOI.
I don't think I would say that as a blanket statement as it depends on the situation, but I would say its probably true for many patients. One one hand, MAOIs have much better evidence of efficacy since they are FDA approved specifically for depression. The benefits of trying pramipexole first though are numerous:
1. On pramipexole, eating certain cheeses, fermented foods and alcohol doesn't make the patient risk death, stroke, etc. There are very strict dietary restrictions on MAOIs given tyramine "cheese effect"
2. For most people, pramipexole will be more tolerable AND will be much less dangerous mixing with other psych meds.
3. A psychiatrist will generally be much more likely to prescribe pramipexole than MAOIs given the above and that it takes very little MAOI in overdose to kill someone
Hi doctor. I would like to know if sertraline (50mg) or paroxetin 75mg, can help to over come this. What other things do you recommend to do to overcome this naturally, easier and quicker? Thanks a lot
I'm curious what's the duration do you have to be The rest of your life could it help someone after 3 to 6 months?
just like any med, it totally depends on many factors. it certainly won't have any effect on anhedonia after you stop taking it though, unless the pramipexole lead to one starting a bunch of goals and hobbies that they then continued after cessation (since Behavioral Activation itself can be a treatment for anhedonia)
I’m hopeing this drug is not like a Modafinil type semi stimulant drug. Do you feel this drug, maybe with a low carb ketogenic diet would improve anticipatory anhedonia, severe slowing and sluggishness, alogia and other negative symptoms increase episodic memories? Do you see any use in “self-disorders/ipseity issues” Wellbutrin or aeuviliy really doesn’t work for anhedonia, wondering exactly how Pramiprexole works for mood as well in schizoaffective related issues with mainly severe negative symptoms, mood symtoms, disorganized symptoms
unfortunately, pramipexole can worsen psychotic symptoms, but not always. Pramipexole is not a stimulant and doesn't cause a "jittery buzz" like classical stimulants or modafanil and does not keep people awake. I've had remarkable success for treating anhedonia with it though. The three main meds I use for anhedonia is wellbutrin, low dose abilify and pramipexole. Good luck my friend.
@@OllertonMDmy issues are really the residual issues of anhedonia and negative symptoms after a first episode psychosis many years ago. Aerobic exercise has consistently always helped my type of anhedonia….but at some point I would like to move on and not have to rely on it and yes…have always been looking for that equivalent excersise in a pill type drug. Is this anything like that by chance or similar in terms of BDNF and its effects on mood? Thanks Doc, glad you are having success with this med
@@Lipolimtown I've seen 2 rodent studies saying pramipexole increased BDNF, and 1 study that claimd the oppostive, so I'm not sure if it increases BDNF. The best evidence for increasing BDNF is SSRIs/SNRIs (which can worsen anhedonia sometimes), exercise, and antioxidant foods like berries. I'm msorry to hear about your episode of psychosis btw :(
Exrcise appears to not only increase tonic dopamine levels, but also upregulates dopamine receptors, which I think is more important. I'm glad exercise has helped anhedonia!
Sir, i suffered with major depressive disorder, i used desvenlafaxine, now my symptoms decreased as much as 70percent, but i am still unable to feel pleasure in many activities, my doubt is i used desvenlafaxine, it can increase serotinin and norepinephrine, but it didn't increase dopamine that's why i am unable to feel pleasure. Sir can you tell me how many months should i take pramipexole and stop it
if you had anhedonia before starting desvenlafaxine, then it probably isn't the cause. if the anhedonia worsened on the med, then it is probably contributing. you are correct that this med wont substantially increase dopamine, and actually boosting serotonin with antidepressants can blunt dopamine signaling in the brain and can indeed make anhedonia or a loss of positive emotions worse.
You are not my patient so I can't make any recommendations about medications or any treatment. What I can say is that any medication for anhedonia will only work for as long as you take it. So some people might have to take pramipexole for 3-6 months, some might take it for years, it just depends on the patient
I have been suffering from severe depression for 8 years, anhedonia and total sexual dysfunction for about 1.5 years. Bupropion was always the only one that helped me, but it stopped working after a few months. Now I'm trying pramipexole, I'm on a dose of 0.5mg for 1 week and still disappointing. I feel sick, , mild nausea, but it has a completely different effect than buropion. My sexual dysfunctions even got worse. But I will try to persevere and increase the dose again. Apparently this drug is my last hope.
nausea is somewhat common when starting pramipexole and dopamine gonists in general. There are many millions of dopamine receptors lining your gut lumen that can increase the movement of the gut and cause GI upset. This is why some ant-nausea meds do the opposite of pramipexole and block dopamine receptors (like metoclopramide). Sometimes the nausea gets better once your gut lining gets used to the extra dopamine signaling.
0.5 mg is not usually a dose I see help anhedonia in my practice. Usually 2-3 mg, if the patient can tolerate it.
I'd talk to your provider about your anhedonia some more if pramipexole doesn't work out for you. There is ALWAYS hope. even if you have tried spravato, there are other options. Anhedonia can likely be caused by unresolved trauma/PTSD, sleep apnea, medications (like SSRIs, antipsychotics, mood stabilizers, lithium,), chronic inflammation (which can be explored by getting a CRP lab, which is easy and cheap to get, and in most states, a person can order it themselves online), high generalized anxiety, etc etc. I've seen anhedonia get better with ketamine infusions, (which of course hits differently than spravato), TMS, ECT, CBT, getting CPAP for previously undiagnosed OSA, etc. There is always hope my friend. And please always make medical decisions under the care of a licensed medical provider.
Stay strong my friend, and thank you for your comment.
Dr O
@@OllertonMD To be honest, I'm a little disappointed with this medicine, I really don't have any nausea at all. I have similar symptoms like flu, fever, sweating, strange smell of sweat. I would accept all of this, but I am most disappointed with how it affects my sex life. I've been suffering from serious sexual dysfunction for a year and a half and I expected this medicine to help me with it, but it made it even worse, I don't even have nighttime erections anymore... At the same time, dopamine agonists are supposed to cause hypersexuality, so why do I have to suffer again? Bupropion was much better in this regard, after a few days I could feel my sexual functions returning, but here it is the exact opposite. I'm currently on 1mg...
Dr. Thank you for your answer, at least I see that you care about patients and suffering people.
How long does it last if someone doesn’t take medication I don’t want to take any medication. I got it from substance abuse for over a year and when I stopped, I don’t feel any pleasure at all. Craving crack again
IIRC one study actually did brain scans of cocaine users and found their dopamine/reward circuitry didn't get close to normal until potentially about 12 months. Depends on how much cocaine was used and for how long of course. Sorry you are feeling bad my friend, hang in there
Beautiful oh god dude if this works. My Anhedonia is so bad and is because of weed trauma depersonalization derealization dissociation. Please keep up with your work we need you so much 😔. Question is it possible for the development of such a drug that gives permanent fix?would prefer detailed answer thank you
thank you for the comment. Please note that continued cannabis use or having unresolved trauma (trauma that hasn't been processed in trauma focused therapy like a full 3-4 month course of EMDR or tf-CBT) will probably dramatically decrease the odds of any medicine, including pramipexole, to work for anhedonia.
unfortuntaly I don't know of any drug that can perminently fix anhedonia. If such a drug were to be designed, it would have to increase neurogenesis in the reward system or somehow increase dopamine D2 and D3 receptor density. The closest thing I can think of that can or likely can do both of these is daily, chronic exercise and avoiding things that can downregulate dopamine receptors, like cannabis and other substances that hammer dopamine receptors.
Good luck my friend
Same bro had dip dr for 30yrs straight and the 1st time and only I felt like I had a normal brain was adderall but only lasted for a half hour, then back to the mind in hell. But what I felt was when I was like 14 when I remembered how normal felt now in my 40s and been trying to figure that way back out again…it just game me hope to start looking for new meds so if I can get my doc to get me this mirapex it’s worth a shot…I’m with ya
@@Bran317 good luck my friend. On average, dopamine meds probably offer the best odds of improving anhedonia in most people, along with anti-inflammatory medicines if brain inflammation is the cause
Can this be used used as monotherapy? Can this be safely used with MAOIs?
MAOIs are essentially never used anymore. I have yet to prescribe one and never had a supervising physician in training that was willing to try one on.a patient of mine, so I don't really know. There is essentially no real-life training on MOAIs in a psychiatrists training. I do know that seleginine and pramipexole are used in Parkinsons disease together sometimes.
Theoretically, I don't see why it would be dangerous. Combining MOAIs with serotinergic medications is very dangerous, but pramipexole is a dopamine receptor agonist, so it is probably safe but have no real-life experience doing that. Definitely talk to your prescriber about this before trying something like that.
In terms of monotherapy, I use pramipexole alone frequently, and works great most of the time
Up to how low have your patients been on this regimen and shown to be effective.
I think my longest run on a patient with pramipexole has been somewhere between 9 and 12 months. I started prescribing it last year while I was still a resident. Haven't had it poop out on me yet, unlike antidepressants, where that happens pretty frequently
even with genetic testind done that shows i have 8 times less dopamine, it has been almost impossible to get doctors to prescribe anything like Abilify or Mirapex until i mentioned i do have restless leg issues. so now i know after years of telling doctors what i needed that i was right and they were wrong. story of my life. its insulting that doctors think people who live in Mexico or thailand are smarter than us living in the USA and yet those people can walk into a pharmacy and get whatever they want in most cases but here in the usa we have to beg doctors. spend the most in the world on medical care and have horrible horrible health in general. big pharma owns us. F that
I’m currently taking adderall as it has been the only thing to do anything. However I’m still bed ridden. Is trying prami along with the adderall I’m already on a bad idea? Thank you so much for any insigh I think my dr is willing to give it a try just didn’t think I should come off my stimulant as I would be comatose without it.
can't give you medical advice, but can tell you I've added pramipexole to adderall without issue in the past. One increasing actual dopamine levels, and one increases signaling at D2/D3 receptors without actually increasing dopamine. So there isn't an absolute contraindication to combine them in general.
@@OllertonMD of course tysm for the reply, i understand to speak with my dr. I just wanted another opinion he said the same thing. Wanted to ask one more question. Have you ever considered l dopa as a treatment? I know it is another treatment for Parkinson's like prami. Wouldn't this have less side effects and a similar effect
@@Timayy I actually have considered it, but haven't tried it yet due to a lack of clinical evidence/human trials. I assume it would work though. Anything that increases dopamine or dopamine signaling in the CNS should improve anhedonia. I don't think l dopa would have less side effects than pramipexole though, as l dopa will cause side effects "below the head" (Ie cause side effects in the body before it reaches the brain). It would probably work better and potentially have less side effects by combining it with carbidopa so it doesn't metabolize and interact as much with the body before reaching the brain. Ie, Sinemet would probably be a better option, similar to how sinemet aka carbidopa/levodopa is usually used together in Parkinsons. Luckily, sinemet is widely available and is a very old drug and thus very cheap. I'll consider using it if pramipexole doesn't work for a patient. Other experimental options I've considered is cabergoline or bromocriptine.
@@OllertonMDmy dr is recommending the sinemet 25/100 mg once daily as he believes it’s due to an inborn error of metabólica with bh4 deficiency. My csf hvaa bh4 and forgot the same of the third was low. Wanted a 2nd opinion if u think the adderall is safe with the sinemet. He seems to think it is of no concern. I could let you know how it goes
@@Timayy I've never prescribed simemet so I have no personal clinical experience with combining the two. I would guess that the two together could be quite stimulating. Both stimulants and sinemet can increase blood pressure so if the two are combined, blood pressure would need to be monitored carefully.
If your doctor thinks you have a BH4 deficiency, you should ask your doctor about methylfolate supplementation though. Its going to be hard, if not impossible, to have normal methylfolate levels without adequate BH4. Luckily, OTC methylfolate has become quite cheap compared to 10 yrs ago. Methylfolate is essential to normal production of serotonin, norepinephrine AND dopamine. I used methylfolate for treatment resistant depressive symptoms sometimes.
Dr. Ollerton, is it true that untreated psychosis can lead to dementia? That’s what my psychiatrist told me.
I’m not familiar with any literature showing untreated psychosis causes dementia specifically, but is has been associated with worse cognition generally, and there is also concern it can also worsen the course of the illness, make psychotic episodes more likely in the future, and might also worsen the more depressive or “negative symptoms” of schizophrenia long term which is a big deal since negative symptoms predict decreased quality of life and increased disability more so than “positive symptoms” like hearing voices and being paranoid or delusional. Psychosis, like mania, is thought to be neurotoxic if it continues untreated.
This is because Positive symptoms are much easier to treat than negative symptoms and cognitive problems in psychotic disorders. Antipsychotics are quite effective for many people to suppress things like hallucinations and paranoia but not so great with treating cognitive problems and negative symptoms like avolition and anhedonia
@@OllertonMD Thank you. That’s very helpful!
Sir, does using pramipexole cause dyskinesia
yes. occasionally. Hasn't happened to any of my patients though. its actually often used to prevent wear-off dyskinesias in those with Parkinsons disease that are taking levadopa
Does Pramipexol cause significant weight gain?
nope!
Every single one of your videos have exactly 267 likes. How do you do that?
If the patient is getting side effects like insomnia, do you ever switch them to Ropinirole?
Ropinrole is effective in depression as well as bipolar depression
Sir can this drug be titrated in 0.5 mg every say 4 days with a target of 3 mg?
Im currently on 1.5 mg with a .25 mg increase every 4 days and very desperate.
No improvement as of yet unfortunately 😔
it all depends on the patient's tolerability and what the prescriber is comfortable doing. I usually increase by 0.5 mg every 14 days, and most patients tolerate this schedule and dosing regimen without issue. This is probably in part due to the fact that my patients that don't tolerate pramipexole know they don't tolerate it right when they start it. AKA if my patients have little to no side effects at 0.5 mg - 1 mg, they usually tolerate higher dosages. The 3 side effects I see that make patients stop it is GI distress, dizziness, or sedation. Besides one patient that had modestly increased urges to gamble, I actually haven't come across any of the more "unique" side effects of pramipexole like psychosis or compulsive behavior.
Good luck my friend, I hope you and your doctor find a treatment plan for you that brings the color back into life.
@@OllertonMD many thanks for the reply Doctor
@@OllertonMD What is the optimal dose or average dose your patients take for anhedonia?
@@paulh3976 my patients usually find relief around 2-3 mg daily
and there is plenty of youtuber reports saying that abilify is frikken nightmare directly from hell
yeah unless one of my patients have a psychotic disorder, I keep abilify to 5 mg or under. At this dose it can boost dopamine and improve mood and motivation. But once you get to dosages of 10-30 mg, it runs a much higher risk of classic antipsychotic side effects like EPS, sedation, etc.
The most common reason my patients decide to taper off abilify is either restlessness or sedation. Occasionally I've seen it increase weight 5-15 lbs too, but that's usually for patients that are on antipsychotic dosages.
Thank you for your thoughts,
Dr O
Does ECT help aith anhedonia? And emotional numbness
yes it does. ECT improves pretty much everything about depressive symptoms and is the most effective treatment for depression that has ever been found.
pubmed.ncbi.nlm.nih.gov/35764228/
Hello sir, I have porn induced anhedonia. I was compulsively watching pornography for many years and I believe my dopamine/reward system is very worn out as a result of extensive porn usage. I have experienced anhedonia and depression as a result of this. Do you think pramipexole would help alleviate those symptoms? Thanks in advance, I am looking for answers as this condition is drastically effecting my life.
assuming you anhedonia truly is from compulsive pornography use, have you tried sustained abstinence from porn? This is purely anecdotal as far as I am aware but lots of people on reddit and other forums claim sustained abstinence resolved the emotional and sexual numbness they attributed to pornography.
Theoretically pramipexole should help with any condition where dopamine 2 and 3 receptors are not being stimulated enough
@@OllertonMD Hi, thanks for your response! I feel very confident that my anhedonia is resulting from compulsive pornography use. I am normally a very upbeat person who has not had many mental health issues throughout my life. I have only had depressive episodes once I started compulsively viewing pornography.
I have tried sustained abstinence and I would say after one month of abstaining symptoms subside dramatically. Managing stress is difficult for me and life events make me prone to relapse. Abstinence is difficult to achieve when dealing with depressive symptoms.
@@Venomenon1000 hold in there man. if you feel like porn use has had a detrimental effect on your life you might want to speak with your primary care doctor about seeing a therapist that specializes in compulsive behaviors. There is little evidence empirically to support this last time i checked years ago, but theoretically, anything that hammers dopamine receptors excessively can probably cause emotional blunting, and removing that stimuli long-term might allow the dopamine receptors to upregulate to normal again. Chronic stress is a widely accepted contributor to anhedonia as well, and many rodent studies show this (ie stressing out rats over and over, like shocking them unpredictably and repeatedly, or putting them in a cage with an aggressive, unfriendly rat, causes depressive symptoms and reduced sugar water consumption, which is used as a surrogate for anhedonia). Managing stress and seeing a therapist for porn use that is disrupting one's life might help, but ultimately, I cant give medical advice to people that are not my patients (I've got to include this disclaimer). I wish you the best of luck and hope you are able to live the life you want to live and I hope you start feeling better soon!
It also down regulates dopamine receptors, what goes up must come down especially with this medication. Medication I've tried it. It did help me come out of a slump
i agree tolerance is a concern for most psychiatrist meds. that's why I am always trying to walk the thin line of the Minimally Effective Dose. If someone has low dopamine signaling (which is practically impossible to ascertain in humans besides those that get a DAT scan, which insurance will usually only cover for those undergoing a Parkinson's Disease evaluation with a neurologist because of cost), theoretically, a minimally effective dose might be able to return someone to normal dopaminergic functioning without running the risk of tolerance.
How long til abilify shows effects?
usually within 2-4 weeks, and fully kicks in by ~2 months. If you are on low-dose abilify for something like depression or anhedonia, I often see people start feeling better after 5-7 days. It takes about 5 days for psych meds to reach "steady state" in the blood, but the full effects take taime. Good luck my friend.
@@OllertonMD thank you so much, all the best to you!
People don't want to be tied to yet another drug.
ideally no one would have to take any drug for any reason, but that's just not the reality for most of my patients, even when I recommend lifestyle change before considering a med. Most of my patients are unwilling to do much in terms of life or behavior change and just want a medication to help them feel better. trust me, I try.
the problem with this drug is that you need to reach atleast 1-1.5mg for it to work and it may never even work and you may need combinational therapy such as Nortryptiline 25mg addon or bupropion or even both
yes most people will need at least 1.5 mg in my experience for it to be noticably anti-anhedonic. The sweet spot I have found for most of my patients is 2-3 mg. Some studies have gone up to 5mg but I've never had to go over 3 mg. Combining with wellbutrin would probably be an awesome combo. I've started pramipexole in those who had already been on wellbutrin for years, but have never started both near the same time, but maybe I should. Wellbutrin happens to be my favorite antidepressant actually.
Thanks for the comment!
How does pramiprexole interact with sex/porn addiction?
it can *potentially* make both worse. Boosting dopamine signaling in general, but especially dopamine receptor agonists, can increase compulsive urges/ behaviors to do pleasure-seeking behaviors. But everyone responds differently. Compulsive sexual behavior is a known risk of pramipexole though.
Can modafinil cures SSRI caused emotional blunting as a dopamine booster ?
Modafinil doesn't just boost dopamine but serotonin as well, so YMMV. I got similar bad reactions from it as from SSRIs, i.e. stomach upset and migraines.
@@p_serdiuk Did modafinil help you after ssri bad reactions ?
the mechanism of modafanil is actually mostly unknown, so hard to say. Its usually just used for excessive daytime sleepiness. I've never prescribed it for anything other than that. Maybe someone that has been on modafanil can chime in.
Any reason why you don’t touch on some of the other benefits(particularly sexual benefits), like lowering the refractory period in men, potentially boosting libido and sexual quality as a whole
this video was meant to focus strictly on emotional anhedonia, but ejaculatory anhedonia and overall sexual dysfunction is definitely a widespread problem. I've never used pramipexole for sexual problems in my patients but I have had a friend or two tell me it reversed their sexual dysfunction from depression or SSRI treatment. will start asking more patients about if pramipexole has improved their sexual health or reduced the refractory period, as this is an interesting area
@@OllertonMD it’s an extremely interesting component of this medication. I myself do not suffer from depression or anhedonia. But I personally use a low dose of pramipexole to lower my refractory period in bed. It’s been great in doing so. I highly recommend gathering more intel on this use case as well. It’s something that people commonly struggle with, especially as they grow older but would still like to continue having sex as if they were 21 again
Hopefully I can convince my doctor that I need a prescription for this.
anhedonia/apathy/depression + (all stimulators are banned in my country even Bupropion) = living in hell
Wow really?? May I ask what country you live in? That’s insane. Are stimulants for ADHD not allowed as well? Good luck my friend
@@OllertonMD any stimulants are banned
(russia) I don't know what to do with this
@@minepolz320 Tell me my friend, how did you become anhedonic, did you use antipsychotics or benzos before? because the cause of anhedonia and the remedies you can research you will find many cases of people like this, don't take buprione it will only make it worse
@@OllertonMDI started taking pramipexole, but unfortunately it just makes me very sleepy, so much so that I can't even stand on my feet. is it worth continuing? in any case, it didn’t make my anhedonia worse, but on the other hand, I don’t quite see any positive effect, now I’m 1 week on a dose of 1mg, just if I’m not mistaken, then agonism to D2 dopamine receptors reduces the release of dopamine causing this side effect
@@minepolz320 yeah they think bupropion is a narcotic, if you abuse it to get a high it literaly sends you in to an epileptic seizure xD
Can I get a MRI scan to detect anhedonia ????
this has only been done in research studies. there is no routine brain scan used to detect anhedonia. I doubt it will ever become commonplace since anhedonia is simply uncovered by the endorsement or denial of a medical symptom by the patient- if someone has a decreased or absent ability to experience pleasure from activities they used to enjoy, that is anhedonia. Some studies have used fMRI studies to show how strongly the reward circuitry lights up during rewarding events, or checking the functional connectivity between the reward circuitry and other regions of the brain.
What about carbidopa/levodopa for anhedonia?
theres been little study on this topic but so far the evidence has been mixed. One negative study on levadopa in anhedonia was in cocaine addicts though, so take that with a grain of salt, as cocain addict's dopamine receptors are profoundly donwregulated. I would supposed levadopa would help people's anhedonia if their anhedonia is caused by low tonic dopamine levels
Please make more videos on anhedonia
ive got 20 anhedonia video ideas i am working on. just recently moved my office space into a new room so hope to be up and running in the next 2 weeks!
@@OllertonMD Thank you so much. I've tried just about everything. Selegiline, rasagaline, pernate, wellbutrin. Nothing works, or causes really bad side effects.. Prami worked somewhat and restored my libido but was side effecty for me. Looking forward to more content, almost nobody talks about this stuff.
Which state are you in please
just in montana for now. I am starting an insomnia telemedicine service with a few friends and we hope to give access to as many patients in different states as possible and once that is up and running, if our system of providing online insomnia treatment works, I I hope to then start an anhedonia clinic online in as many states as possible. AFAIK, this would be the first anhedonia clinic in the world. I'm guessing this is a few years out though.
That sounds good! It also sounds as if it is truly needed. I'm in the UK
@@nicolavowles2930 unfortunately I wont be able to see patients outside of the united states due to licensing laws in the United States, but I hope to come out with an ebook and udemy course people can take for those that are unable or cannot afford to see me. I plan on also posting a free pdf soon of promising medications and labs anyone in any country can bring to their doctor that might help them heal from anhedonia
or maybe in the future if the clinic is viable, I can hire practitioners in other countries that I train that can be the providers for patients outside of the US. Come to think of it I really like this idea. We will see how things pan out! Currently have another 1.5 yrs of my current contract I need to fulfill at my normal 50 hrs a week job so will probably be in a few years, but I hope to come out with other material people can read and watch in the meantime. I'm currently converting a room in my house to a video studio/workspace so I can get to work on this stuff soon!