I'm currently fighting to withdraw from dopamine agonist (DA) after a severe augmentation. I was prescribed some other drugs to help me go through this process (tramadol, pregabaline, clonazepan, wellbrutin). My plan is to get back to my pre-DA RLS baseline level, and to treat them with pregabaline only.
Is this plan realistic? Or do DAs do permanent damages to the brain, leading to much more severe RLS that can only be treated with strong opioids like methadone?
Is there any study that has demonstrated permanent brain damages from DAs?
Thanks
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Mikatrap
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If you are on DAs for a long time, your dopamine receptors can be damaged and pregabalin won't work. Your RLS won't be more severe as a result though. But you won't know whether they have been damaged until you have been on pregabalin after you are off your DA for several weeks and then you begin to increase the pregabalin by 25 mg every couple of days until you reach an amount that controls your RLS or to the maximum which is usually 450 mg although you can take as much as 600 mg.
Thanks Sue. I've been on DAs since 2021, and on small doses of pramipexole most of the time (0.19 to 0.38mg). Well, we'll see when we get there.
What I don't get is how DAs could lead to permanent damages. If some receptors are damaged by DAs, they won't be effective, so the neuron will notice that it is not triggered enough by dopamine and it should just create more dopamine receptors. Furthermore, I thought that proteins on the surface of a cell are not there for ever, that they are constanly created and destroyed. Maybe not for neurons?
If you have a scientific reference on permanent brain damages by DAs, I'm interested!
Study: The study reviewed the pathophysiology and treatment of augmentation in RLS.
Findings: It suggested that chronic DA use might lead to downregulation and desensitization of dopamine receptors, particularly D2 receptors, which could exacerbate RLS symptoms over time.
Citation: Garcia-Borreguero, D., et al. (2016). Pathophysiology and Treatment of Augmentation in Restless Legs Syndrome. Sleep Medicine Reviews, 29, 104-114.
Trenkwalder et al. (2011)
Study: This study analyzed the long-term effects of DA therapy in RLS patients.
Findings: It highlighted the development of augmentation and suggested that chronic stimulation of dopamine receptors might lead to adaptive changes in the dopaminergic system, such as receptor downregulation.
Citation: Trenkwalder, C., et al. (2011). Augmentation in Restless Legs Syndrome is Associated with Low Ferritin. Sleep Medicine, 12(6), 524-529.
Allen et al. (2011)
Study: This study focused on augmentation and its implications in RLS patients.
Findings: The researchers discussed that chronic DA treatment could lead to receptor changes, including downregulation and alterations in dopamine transporter function, contributing to augmentation.
Citation: Allen, R. P., et al. (2011). Restless Legs Syndrome: Diagnostic Criteria, Special Considerations, and Epidemiology. Sleep Medicine, 12(8), 853-864.
Morgenthaler et al. (2006)
Study: The study reviewed augmentation in RLS and the effects of long-term DA use.
Findings: It indicated that persistent stimulation of dopamine receptors might lead to compensatory mechanisms, such as receptor downregulation, which could exacerbate RLS symptoms and complicate treatment.
Citation: Morgenthaler, T. I., et al. (2006). Practice Parameters for the Treatment of Restless Legs Syndrome and Periodic Limb Movement Disorder. Sleep, 29(8), 1088-1102.
Preclinical Studies on Dopamine Agonists
Study: Preclinical studies on animal models have provided insights into the long-term effects of DA therapy.
Findings: Chronic DA administration in these models has shown receptor downregulation and changes in dopamine transporter levels, suggesting potential long-term alterations in the dopaminergic system.
Citation: Qu, S., et al. (2007). Increased Locomotion and Dopaminergic Gene Expression in the A11 Diencephalospinal Dopamine System in Restless Legs Syndrome. Brain, 130(9), 2484-2493.
You have a long road ahead of you--- to get off all those drugs.
But you will do it.
By going very slowly and by small increments.
It will take a while for the Pregabalin to have any effect-- fighting through the haze of withdrawal RLS from all those powerful drugs.
You may well have to take some sort of opioid in the distant future for refractory RLS, and that's ok.
At that time ,you will have to experiment with different opioids, as people have varied experience from them.
Some can tolerate methadone or buprenorphine or hydrocodone / Oxycontin --- whichever suits you or you are able to get prescribed.
FWIW. I've been on Oxycontin for 8 years now and have had no side effects, except at the start with some insomnia and itching. But just for about 3 weeks.
Good questions, for which there are no real answers or studies. DAWS is very real, but there are no studies on how many patients have been affected or whether recovery is possible.The top US experts, who see thousands of RLS patients every year, report anecdotally that some of their patients never recover.
I was successful in withdrawal from pramipexole (15 years on DA). It took a year or so with occasional use of hydrocodeine, acupuncture to treat my very sensitive nervous system (aching leg muscles and poor sleep) and regular exercise that included stretching of my leg muscles and walking 1-2 miles per day. Now, 8 years later I am mostly free of RLS with bedtime dose of 100 mg Gabapentin and the use of red light/ infrared light treatment . If on occasion I have a breakthrough of RLS, I use a massage gun on my leg muscles which usually resolves the issue pretty quickly. It was a long process to figure out what worked. After I had completed withdrawal I had good results with Gabapentin at 100 or occasional 200 mg at bedtime. After 3-4 years I felt the Gabapentin was less effective.
After I fractured some bones in my foot and could not exercise, RLS became an issue again. I took iron tablets which helped. My daughter wanted me to try the red light therapy to help with bone and tendon healing and I noticed after 2 weeks or so of nightly red/infrared light on my feet and legs that my RLS was gone and my sleep was much improved. I stopped the iron but have continued to take Gabapentin.
I don't know of any research into the damage to the dopamine receptors in the brain. I think that is just a hypothesis that is yet to be tested.
I use the Redjuvenator biophotonic light #3 formula which has red light (visible) + NEAR IR (invisible) . I purchased it online from Leanne Venier leannevenier. com. I checked out others but because I had such great results with this light (that I was borrowing from my daughter) I bought the same one. I put the light on my legs (my ankles and calf muscles) every night for about 30 minutes before bed. Leanne has very specific protocols for muscles and tendon issues and more but I don’t use them regularly. She includes more information with purchase. Using the light has also improved the quality of my sleep and my ability to fall asleep more quickly.
I think most, if not all, of your problems stem from withdrawal from Effexor. But so what? It is what it is, right?
Here you are talking to us in real time. Real time!!!
“From Feb to Aug 2023, I tapered off Venlafaxine gradually... and it was awfull. In fact, quitting Venlafaxine has been the worst experience of my life. A few weeks ago, I had a complete 'crash' of my nervous system, with as symptoms nausea, extreme anxiety, asthenia, chills, tremors, etc. I'm still in the midst of this crash. I know that it will get better with time, but it's really super-hard.
Anyway, I want to stick to my plan and I started to taper off Mirapexin a few days ago. I replaced my Mirapexin 0.26mg evening dose with a Pramipexol 0.18mg dose. Directly, RLS symptoms worsened. To be able to sleep, I now have to take Tradonal 0.5mg every night, else I could walk all night. My neurologist recommends me an aggressive tapering off: a few days on 0.09mg, and then nothing. But I'm afraid that my withdrawal symptoms would become so severe that my nervous system, which is already in pretty bad shape with the Venlafaxine withdrawal, would totally collapse.”
Mika, you had a complete nervous system crash BEFORE reducing the DA. As you reduced the DA a small amount of Tradonal enabled you to sleep. I believe the DA was the only thing keeping you from feeling the full-on aftermath of withdrawal from Effexor and that in reality your RLS is mild. A DA would help even a non-RLS person with withdrawal from a 28 year use of an SSRI/SNRI.
Once completely off the DA you were hospitalized and told us the following, in real time:
“Each evening, I take a ritrovil and a Tradonol, and I sleep well the whole night. But each morning, I wake up with an anxiety attack. I have my 'good' windows in the afternoon generally. The rest of the day, I'm depressed and anxious, and my RLS can make my legs shiver like crazy.”
We on here hope, pray and hold our breath that once off the DAs members will be able to sleep “well the whole night” with a small amount of Tramadol and Klonopin, as you are. You didn’t even awaken with RLS, you awoke with anxiety and panic that persisted most of the day that also left your “legs shivering like crazy.” I believe it’s the anxiety and panic from Effexor withdrawal that makes you shiver and tremble, not RLS or DAWS.
You were on low dose DA for around three years because the Effexor made your legs go crazy. We’ve had people on high dose DAs for 25 years with none of the symptoms you describe. Not only didn’t they have your symptoms, they weren’t able to sleep like a baby each and every night once off the DA, as you did, with only a small amount of a weak opiate.
Is it possible that DAWs is what is causing your daily nervous breakdown? I guess? Is it likely? No. When you go back on the DA you feel somewhat better NOT because you have severe RLS or DAWS, it’s because the DA is helping with the symptoms of Effexor withdrawal. When you reduce the DA, those Effexor withdrawal symptoms rear their ugly head.
Time is your friend. You might as well stop worrying that the DA or Effexor did permanent damage and instead “over treat” the symptoms. Take anti-nausea meds and peppermint oil and papaya enzyme for nausea. Alternate Tramadol and Ibuprofen or Naproxen for body aches, along with heating pads everywhere. Take the benzodiazepine when you can no longer iron butt your way through the anxiety and panic.
Treat the physical symptoms and stop worrying that you fried your brain. You didn’t, but you will make yourself crazy if you convince yourself of this. Though I believe Trazodone has the tendency to slightly worsen the symptoms of RLS, your RLS is so mild that I believe the additional serotonin the Trazodone provides (which Wellbutrin doesn’t) is worth it. Any additional RLS symptoms (if there even are any) should be readily covered by the Tramadol.
There was a part missing in this first post. I stopped Venlafaxine on July 31, 2023. On Aug 15, I cut my Mirapexin 0.26mg in half. On Sep 2, I had a CNS crash. The tremors that I mentioned were only in my legs, and I’m pretty sure it was RLS. I got back to my full dose of Mirapexin and most of my symptoms vanished, anxiety included. Two weeks later, I had another CNS crash. Then my neurologist told me to go from Mirapexin 0.26mg to 0.19mg, my condition got worst, with a crazy RLS day and night, shiver, anxiety, etc
Anyway, now I’ve been back on an antidepressant, Wellbutrin, for 2 weeks. Since then, my RLS worsened terribly. I have it day and night, and it is extremely painful.
My guess is that the cause of my misery is my double withdrawal from DA and Effexor. My CNS can’t find a balance, and I suffer like crazy from a constant and very painful RLS.
No, I’m not anymore. I have to take 150 to 200 mg of tramadol and 1.5 mg of clonazepan to get knock out and sleep a few hours. I’m waken up around 3 in the morning by my painful RLS, and I can’t sleep anymore even if I take more Tramadol and clonazepam. And this damn painful RLS lasts all day long
I don’t think it’s RLS. Your post from two months ago describe symptoms that match SSRI/SNRI withdrawal exactly. 99.9% of time RLS is relieved by standing and walking. The problem isn’t so much horrendous pain, seizures and shaking (your described symptoms) as it is lack of sleep. And if anything, most symptoms of pain, depression and anxiety during DAWS are from that lack of sleep. You slept well in the hospital (8 hours), with a low dose weak opiate, but still had strange non-RLS like symptoms all day long???
When you describe a level 8 or 9 PAIN, that envelopes your body and sends electric currents through-out and waves of nausea and epilepsy like seizures, regardless of position, you are not describing typical or even atypical RLS. Two months ago you also describe sleeping like a baby for 5 to 6 hours a night. A person with true DAWS would kill for that and then be ok having to keep busy standing and walking during the day to keep the RLS at bay. Does walking relieve your symptoms Mika?
You are doing yourself a disservice by calling your seizures, electrical currents, and killer pain RLS. I don’t believe any one on here is qualified to advise. There are very specific drugs that can help with SNRI withdrawal including substances like Benedryl, Tylenol, Ibuprofen and possibly Trazodone, rather than Wellbutrin. Less focus on dopamine and more on serotonin, possibly?
You’re very good at research, find all of these somewhat innocuous substances, use them judiciously and keep beating back the physical symptoms, day in day out.
My pain originates from my lower back. At first, it is an unpleasant feeling that extends to my legs. I have to move them to get relief. The feeling can then become very painful, like a periodic electrical shock in the lower back extending to the legs, and sometimes to the upper body. When it happens, I can’t resist moving my legs. Yes, walking gives me some relief, but sometimes the shocks in the lower back persist. Three neurologists have witnessed one of my crises and called it a very severe RLS. The more I progress in my DA withdrawal, the worst it gets. It can last all day and night. These last three weeks, I have slept only a couple of hours per night, and I need now 150 mg of tramadol and 1.5 mg of clonazepan to get this sleep.
My neurologist thinks that my condition is due to my withdrawal from Venlafaxine and pramipexole, and that my serotonin, noradrenaline and dopamine systems are all three out of balance. I had a clear RLS augmentation before this double withdrawal. I had RLS during the day, and I couldn’t stay quiet at cinema or in a plane. This is why I decided to do this double withdrawal.
The reason why I was sleeping well a few moths ago is simple. Until October, I was on 0.26mg pramipexole = 260 mg levodopa equivalent. Last November, after my DA cold-turkey withdrawal and my complete nervous system crash, they put me on 2mg rotigotine = 600 mg levodopa equivalent. In other words, they drastically increased my DA dose well above the initial one. It calmed down my RLS, but not my SNRI withdrawal symptoms. Now my rotigorine dose is 1mg, low enough for my RLS to come back in full force.
So I think that you’re partially right. I probably don’t have a real DAWS. I have a combination of withdrawal symptoms from an SNRI that I took for 28 years, and from a DA. As my augmented RLS is more and more severe as I progress in my DA tapering, my neurologist decided to fight my anxiety and depression crises with a the only AD that does not increase RLS, Wellbutrin. It doesn’t help on the serotonin side, but it should still ease my psychological symptoms and help me complete my DA withdrawal.
I have an appointment with a first-grade Spanish RLS expert. We’ll see if he can help me.
Thanks for the tips on the drugs able to ease SNRI withdrawal symptoms. I’ll dig into them.
The first-grade Spanish expert suggests me to INCREASE my Neupro from 1mg to 3mg, and to increase it more when augmentation will come back. This is definitely not the road I want to take.
OK, I'm so fed up with my DA withdrawal and its huge impact on my life that I decided to do something radical (and stupid): to accelerate my tapering off. I slowly went down from 2mg to 1mg Neupro from Dec to June, and it has been hellish. So within the last two weeks, I went down from 1mg to 0.5mg, and today I stop Neupro completely. I'm now bracing for impact. I have had a lot of pain and of psychological effects these last two weeks, but I already had a lot before, so it doesn't change much. I'm stuck at home, I can't go back to work, my partner is gone, I don't see my kid anymore, so what do I have more to lose? I'm gonna stop the other meds too (pregabaline, tramadol, clonazepan) to take a real "drug holiday", take another infusion of iron to keep RLS at bay, and then I will adapt my medication to fight any remaining symptoms. My brain is supposed to be fine, without any permanent damage, so it should heal at the end. We'll see.
Hope it goes well. I had Daws a few years ago after being on low dose of Pramipexole. 0.375 for only about 18 months. I noticed early when taking it my rls was way worse and my anxiety started creeping in. The more I researched (including finding healthunlocked) the more I realised my downfall was likely DA initiated.
I began withdrawing and was very determined to get off it. After about 3 weeks I had completely stopped 2 days later I crashed. I was unable to get out of bed, I felt so tired, anxiety was through the roof. It was absolute hell. After 3 days in bed I realised I'd come off too quick and took half my original dose. After a few hours I started feeling better, far from perfect, but I was able to get out of bed.
I end up tapering off super slow over 8 months or so. It was hell, I felt terrible every waking hour. However the healing didn't really start until I was completely off it. It took another 6 months or so to start to feel better. 12 months and I was confident I'm likely as healed as I will ever be.
I wouldn't wish this upon anyone and hence why I follow up and read comments around the topic. All the best, it does get better
How are you doing? Just read through your posts. Sorry you’re having such a terrible time. I particularly noted your experience of back and leg pain mixed in with RLS. I have lifelong RLS and I am a chiropractor. Always suspected there’s a link with my own low back mechanics and my RLS symptoms.
Thanks for asking. I'm not so well, see my post below.
Yes, I also suspect that there is a link between my low back nerve anatomy and my RLS. MNR showed that I have a small herniated disc at L4-L5. They treated it with infiltration. It did not improve my symptoms.
Stopping abruptly my Neupro was far from a good idea. My 24/7 RLS became more and more painful, so much that I spent most of my days crying and screaming with pain. My only relief option was to go to bed and knock me out for a few hours with 1mg of Clonazepan. Anxiety and depression went through the roof too, to the point that I considered suffering from dementia. I had a lot of suicidal thoughts, and swallowing 100mg of clonazepan to gently stop breathing seemed more appealing every day.
I thought that the worst part of the withdrawal would last 2-3 weeks or so. After a month, I was not yet at the peak, my pain and psychological symptoms were still increasing. 3 days ago, my parents found me in a pathetic condition in my house and brought me to the ER. I was directly hospitalized in the neurology department ... for the 7th time in 10 months.
They gave me back 1mg of Neupro. My current medication includes also 3x100mg of pregabaline, 2x100mg of tramadol, 0.5mg of clonazepan. They also tried to give me some amitryptiline to decrease my pain, but it is a RLS-unfriendly antidepressant, so I prefer to do not take it. The first day, my pain was so severe that they had to give me oxycodone too. Yesterday, I started to feel better, probably thanks to the re-introduction of Neupro. Today, I had a lot of pain and a strong depression crisis, but I still feel better than a few days ago.
My neurologist is on holiday, and the other neurologists here do not have a lof of experience with DAWS. He told them by phone that if my condition does not improve within a week, they should increase my Neupro to 2 mg, which would destroy 7 months of painful tapering off.
Honestly, I don't see any light at the end of this long tunnel...
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