04/03/23 Edit : In hindsight, with apologies to those have already responded - though I think the body of the post communicates the concern better - I wish I would have titled this post “Is the risk of developing DA augmentation overblown?”
Also, I’ve had some unexpected issues come up but will respond to everyone asap.
I intermittently check in here and find a lot of support and good information. I’m writing for a couple of reasons:
Lately, I have been concerned about information that is leading to what, in my opinion, appears to be an unsupported demonization of the historically, most studied and most effective RLS/PLMD medication class - Dopamine Agonists. The concerns are primarily due to the risk of and experience with augmentation. However, I thought it would be helpful to hear what the 2021 Mayo updated recommendations state with an excerpt (below). I’d rather have more ”tools” to deal with RLS/PLMD than less. At this rate, with public opinion and, the overzealous cautions of experts and websites, one day DA’s may not even be an option. That would be a limitation and a shame. We need all the options we can find. Promise, I’m not a big pharma rep..
Also, as I’ve never experienced augmentation or DA withdrawal but hear that it’s hellacious for many people and, that I may go through it one of these days, I’d like to hear people’s experiences with it and under what conditions they occurred. There’s also DA ”rebound” which is different but sometimes a part of DA discontinuation so it would be good to know which occurred.
A couple of things that stand out below:
- there an 8% chance in any year that you develop augmentation
- not all DAs carry the same risk
- developing impulse control disorders are as likely and up to 2X as likely
- there are ways to minimize your risk of developing augmentation
- there are ways to minimize it if and when it does occur
“Two major problems often limit the use of dopamine agonists, which is why they are not recommended as first-line agents unless there are contraindications to alpha2-delta ligands. The single and by far most common problem is disease augmentation (onset of RLS symptoms earlier in the day after an evening dose of medication, spread of symptoms to the arms, paradoxical worsening of symptoms with dose increase, and shorter effect of each dose of medication; For pramipexole and ropinirole, this occurs in about 40% to 70% of patients during a 10-year period or at an annual rate of 8% per year for at least the first 8 years of use. Augmentation frequency with the rotigotine patch may be slightly lower at 36% after 5 years. The risk of augmentation is dose dependent, thus the great importance of not exceeding recommended maximum doses.”
“A second common adverse effect of long-term dopamine agonist use is impulse control disorder, with rate of occurrence estimated to be between 6% and 17%. Before dopamine agonist therapy is commenced, patients should be questioned about a history of impulse control disorder, although the disorder may occur for the first time on starting the drugs. An impulse control disorder, which may be manifested as pathologic gambling, impulsive shopping, or hypersexuality, commences an average of 9 months after introduction of the drug {I can imagine situations when an Impulse Control Disorder could result in a rapid discontinuation of a DA and lead to horrendous rebound symptoms}. Both these serious adverse effects should be assessed at every follow-up visit. If augmentation is mild (predominantly manifested by symptoms starting less than 2 hours earlier in the day), consider initially splitting the dose with some of the drug administered at an earlier time. Use of extended-release pramipexole or ropinirole can be considered, generally without increasing the total daily dose, although limited data are available on their use in RLS. If an increase in total dose of dopamine agonist is deemed necessary, careful monitoring is essential to detect progressive augmentation. If augmentation progresses after the second increase in dose, another increase should not be made. Subsequent choices include maintaining the dose, replacing oral agents with the rotigotine patch, adding another agent from a different class, and discontinuing the drug. Discontinuation of dopamine agonists because of severe augmentation or other adverse effects and substitution of a drug of a different class (such as an alpha2-delta ligand) can be achieved in 2 ways. The initial drug can be reduced slowly after the new agent is introduced with an overlap period when the patient is taking both medications. Alternatively, the initial drug can be reduced and discontinued with a drug holiday before the new agent is introduced. Higher doses of dopamine agonists should never be discontinued abruptly as serious withdrawal effects can occur, characterized by severe RLS, sleep disturbance, and depression. Rates of reduction should not exceed 0.25 mg (pramipexole) or 0.5 mg (ropinirole) every 3 days. Whereas a drug holiday can allow a new symptom baseline to be established, many patients with augmentation from dopamine agonists find it difficult to tolerate a period free of any medication, with exacerbation of RLS and profound insomnia lasting sometimes a week or longer after complete discontinuation”.
So yes, an 8% and 7-17% chance major problems can occur. Importantly, the studies these percentages are derived from were determined well BEFORE there was wide-spread awareness of augmentation - it’s causes, precautions, mitigators and clinical responses to it. Therefore, it stands to reason that due to increased patient and physician awareness, the risk of developing augmentation and mismanaging it will be reduced in the coming years while the ability to manage it successfully when it does occur will improve.
Let’s be cautious and aware, but let’s keep DA’s on the menu. We may need them one day.
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ircam2112
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This sounds like it was written by someone who has not gone through the hell that is augmentation. My business and my life was destroyed by this drug. There is a reason the citizens had to sue the FDA (and won) to put warning labels on DA drugs.
Google “Ropinirole Lawsuits”, since DA drugs are different try “pramipexole lawsuits” How many people have to have their lives ruined so the pharmaceutical companies can live?
I guess nobody speaks with the doctors about get a morning fasted full iron panel before prescribing DA drugs.
I’m really sorry to hear that. I do say above that I haven’t experienced augmentation but would like to hear more. When I tried both Ropinorole and Pramipexole back in 2003, it didn‘t do my any favors either. I first was discontinued from antidepressants way to quickly to create the RLS/PLMD and then when treated for that, not warned about impulse control issues, which significantly impacted my life. And, since GSK (Requip) appears to have known about the impulse control issue problems as early as the late 1990’s, through the experiences of treating PD patients, it is criminal that it took the FDA until 2014 to force/require them to add the warning to the prescribing information for Requip. I’ll do some research on Mirapex lawsuits.
I was on ropinirole for six years and recently tapered off, which was Really difficult. It’s essentially a month process (2 weeks to taper, two weeks no drugs) to do it right and I had to work through most of that on very little sleep. There is nothing like personal experience and reading about many many other peoples similar experience for me to understand that DA’s are not a great treatment.
Regarding augmentation, I can tell you, now two months off the drug with a two week period after tapering off and being on no drugs, that the augmentation was way way worse than I realized while I was on ropinirol. One cannot know this until you’re actually off the drug and not on anything for a couple weeks.
Augmentation can take many forms in for me it included spreading to other parts of my body, and a significant increase in bladder activity. quality of sleep that was getting progressively worse is also now much clearer. None of this was obvious while I was on the drug.
And the impulse control was there also mostly around rash decision making especially when it came to buying shit I really didn’t need.
After that two week, period and the DA was completely out of my system, my symptoms were approximately 70% less than when I was on ropinirole. It’s amazing how much less severe my RLS is compared to being on ropinirol.
I can go on and on here With more detail, but suffice to say all of the other posts here that are similar to this experience I had are not overblown in my opinion.
After weeks of working on the titration, I’m now on low-dose opioids of 10 mg with two doses in the evening and before bed.
For me, the reward of going through that taper and two week period of no drug was well worth it. My quality of life has increased considerably.
Thanks for your response. Sounds pretty rough. So, correct me if I’m misinterpreting, but it sounds like you were experiencing augmentation while on the Ropinirol but that it was such a gradual process of worsening that you didn’t recognize the full impact it was having until you stopped it.
Are you able to look back and determine when the drug started to be more harmful than helpful? Sounds like you maybe had a few years when it was definitely an improvement?
Hindsight is 20/20 and different doctors have different ideas, but after 6 years it sounds like two weeks is a pretty short window to taper off, especially if you were taking a higher dose. I’m beginning to reduce from 3mg Neupro - it just doesn’t seem to be helping as much as it was when I began it 4 months ago, though still improved (it sounds like having a firm memory of how symptoms were when you started the DA is an important guide to when augmentation may be beginning). My doctor wants me to take 1 month to taper off completely - 2 weeks at 2mg and 2 weeks at 1mg. If things worsen, I may go back to the 3mg dosage and am thinking about asking doctor to add Pregabalin or Gabapentin during the process.
I knew it was getting worse. I just had no idea until I went off and just how bad and how much more widespread it was. I was aware that it was in my arms and particularly in my hands, but really didn’t understand the other symptoms it was created. Particularly the over active bladder, the change I attributed to just getting older lol.
I’ve been working with Johns Hopkins, who am I to argue with their taper protocol, they have an enormous library of treatment and research from their research team. When I asked about drawing out the time longer, they said all of their experience has been that all that does is prolong the unpleasant withdrawal symptoms.
The first two years ropinirol was a great treatment, but my general doctor who prescribed it had no idea about the long-term implications or alternatives.
You may find that too fast, although you may not since you have only been on it for 4 months. The usual recommendation is .25 mg every 2 weeks and letting it settle before going on to the next reduction. On gabapentin/pregabalin the beginning dose is usually 300 mg gabapentin (75 mg pregabalin). Start it 3 weeks before you are off Neupro although it won't be fully effective until you are off it for several weeks. After that increase it by 100 mg (25 mg pregabalin) every couple of days until you find the dose that works for you. Take it 1-2 hours before bedtime. If you need more than 600 mg take the extra 4 hours before bedtime as it is not as well absorbed above 600 mg. If you need more than 1200 mg, take the extra 6 hours before bedtime. (You don't need to split the doses with pregabalin) Most of the side effects of gabapentin or pregabalin will disappear after a few weeks and the few that don't will usually lessen. Those that remain are usually worth it for the elimination of the RLS symptoms. If you take magnesium take it at least 3 hours before or after taking gabapentin or pregabalin as it will interfere with the absorption of them and if you take calcium don't take it within 2 hours. According to the Mayo Clinic Updated Algorithm on RLS: "Most RLS patients require 1200 to 1800 mg of gabapentin (200 to 300 mg pregabalin) daily." Check out the Mayo Clinic Updated Algorithm on RLS which will tell you everything you want to know including about its treatment and refer your doctor to it if needed as many doctors do not know much about RLS or are not uptodate on it as yours obviously isn't or s/he would never have prescribed a dopamine agonist at Https://mayoclinicproceedings.org/a...
I was on Pramipexole for 20 years. Early on I experienced augmentation and by pure chance I discovered Codeine helped - so with my Docs permission I had to stop the pramipexole every 2 months and go on to Codeine for a week, then with the 'clock reset', back on the pramipexole. It was never ideal - but I stuck at this for 20 years. Eventually I ended up in a guddle where nothing was working well so my Doc decided to try something else. I stopped the Pramipexole.... and what hell ensued. I plunged into the most hideous depression, anxiety and insomnia. This was 2 years ago. I had no idea why I was feeling the way I was which made the anxiety even worse. Google became my friend and I stumbled upon DAWS and this forum. DAWS explained exactly what I was going through. Well, 2 years on and I am still struggling. It has been terrible. Thats my story - hope it helps.
So sorry, Gary! I wonder why things are still be so bad 2 years later? Do you have a top doctor who can explain/help? I know DAWS is intense but I did think it had solutions. Hang in there-I know-it all sucks.
Its hard to know what is causing what at the moment. All meds have side effects and I have just not found a workable solution yet. As you say - it sucks!
That’s an awful way to end what sounds like a pretty successful period of management. I’m actually thinking of the a similar treatment approach - one in which I’m on DAs for 4-6 months, then slowly transitioning to a different DA or Pregabalin or Gabapentin, then back to a DA after a period of clearance - maybe DA 4-6 months, A2 ligand for 1-2 months, repeat.
May I ask how long you took to taper off the Pramipexole? I’ve actually been through something similar/related. When my doctor ordered a rapid discontinuation of Sertraline (Zoloft) back in 2004, my RLS/PLMD began 2 days after the last dose. Besides that and all new, I began to have daily depression, diarrhea, “floaters” in my vision, dizziness, anxiety (which I now realize is more like akathisia or inner restlessness), bruxism and other symptoms. The depression, akathisia, bruxism and PLMD continue. Sertraline has a relatively strong affinity for the dopamine system. Antidepressant Discontinuation Disorder (ADDD) or Antidepressant Withdrawal Syndrome (AWS) has similarities to DAWS, including new or worsening anxiety, bruxism, depression, parathesias, like RLS, PLMD and Myoclonus, etc.. The only recommended treatment I’ve read about (Wikipedia search ADDD) is to go back on the same medication, same dosage and then taper off very, very slowly. It might be something to consider.
I did it last year after years of fear about taking Sertraline again. I was going through other medication reductions at the same time and it did seem to help with those changes and also seems to have “mellowed” my PLMD a little i.e. moved them more consistently to the upper body and less violent, now more like 80% twitching with big movements the other 20%. The movements are still causing sleep disruption/arousals, but all-in-all, the process doesn’t appear to have made anything worse and probably a slight improvement in depression and akathisia. A good enough improvement that I’m considering doing another trial and slow taper. Maybe a series of them will help calm some of these long-term symptoms.
You might consider starting berberine-salem lake has a theory that it could help repair our damaged receptors. Just an fyi. She and I have had many exchanges about it on this forum.
It sounds like you have a good understanding of all the issues involved and similar experiences. My Doc had not heard of DAWS so he just said stop the Pramipexole. That was the problem.
Even though i was on it for 20 years, looking back I can see Pramipexole definitely gave me impulse control issues. I am so glad I am off it. It never worked 100% and was always problematic. TeddiJ from this forum suggested I try Kratom so I bought some. It works perfectly for me - I have no rls at all. It does cause insomnia though. But I am so glad I am off Prami despite the ongoing issues.
The only problem with your switching back and forth idea is if you are on a high enough dose of pregabalin or gabapentin to be effective is that you have to very very slowly slowly come it to avoid withdrawal effects. If you do so slowly enough you shouldn't have any.
From posts on this formum it’s clear that DA’s can work for some people for long periods without augmentation. On the other hand many people report serious issues with pregabalin and even opioids so there’s no single medication which works for everybody and comes without side-effects. With DAs, however, there does seem to be a relatively high chance of serious side-effects, which may leave irreversible changes to your dopamine receptors and withdrawal is often a difficult and very unpleasant experience. so while I believe DAs should remain as an option, they should be very much a last option when other routes have failed, and if there is no alternative other than severe RLS. In all of these cases Doctors should be giving a full and clear explanation of the benefits and risks so patients fully understand what they are taking on. I personally hate taking medication and came off pregabalin because I didn’t like the experience and preferred to manage my symptoms in other ways. However, if I was older and my RLS was very severe than I would certainly consider a dopamine agonist after all other avenues have been exhausted.
Hi, I was taking 300mg a day for neuropathic pain, in two 150mg doses 12 hours apart, 8am and 8pm. I got my tablets changed to 75mg so I was taking 4 a day and then I reduced by one tablet at a time, waiting a few weeks to see what changed, whether I was feeling more sensations and whether my anxiety levels had increased. That gave me some confidence that I wasn't going to experience a big change that would worry me and make me want to go back up to the previous level. I reached 150mg a day (2 x 75mg) over a month or so and then left it like that for a several of months as I was doing more travelling and exercise which I thought might aggravate my symptoms and that worked OK. I was quite comfortable with the increase in activity and also the reduced dose. I then dropped another tablet for a couple of weeks and then finally being very cautious I tried taking a tablet every other day although I don't really think that was necessary at that point because one tablet isn't really doing very much. I told myself I could go back up a level at any point if I was worried so there was no need to get stressed and I found that quite calming. Once I was completely off the pregabalin my head was definitely clearer and I could see the effect the pregabalin had been having although it wasn't massive e.g. I wasn't walking around in a fog, or unable to function. The pregabalin was useful to allow me to get used to the new sensations with the nerve pain and to worry less about it so overall I think was a valid thing to do but I'm happier without and am lucky enough not to need it for the RLS.. yet.
Thanks. Yes, I was very surprised to see that in one of the referenced studies in the Mayo paper re: Pregabalin, that Pregabalin caused augmentation at about 1/3 the rate of Pramipexole. It make me wonder if part of the worsening when discontinuing DAs is the natural worsening of RLS over time that gets “hidden” by the drugs but then is revealed when the DA is stopped.
But overall, it seems like early identification of augmentation is most important and then when discontinuing, to do it very slowly. Probably more slowly than we’re doing it now even. In my opinion, doctors are about 15-20 years behind on research in this area.
There’s one study that has always stuck with me (and its results have been repeated), is that approx. 50% of people undergoing opioid detox develop RLS and/or other movement disorders, some for extended periods. The dopamine system is, I believe, the most ancient neurotransmitter so any dealings with that system (hunger, sex, food, etc) are fraught with dangers. No bulls in the China shop.
Oh ircam2112! Don't ever tempt augmentation. My husband was taking Mirapex (Canada) for a couple of years, starting in 2019, to combat refractory RLS. At first, it seemed like a miracle drug. We even sent a card to the pharmacist who had recommended it, thanking her. Then, gradually his symptoms started worsening. I started keeping a food/medication journal and at times he was down to 12 hrs/sleep/WEEK. The scariest symptom of augmentation was that he would INSTANTANEOUSLY fall asleep. When driving on a 6 lane highway, pulling an RV, Any random time. He withdrew from Mirapex and at the same time gradually started to take Gabapentin. Our doctor was unaware of augmentation at the time and prescribed a one week changeover. Ircam2112, in my husband's 68 years of life, he has never been as close to feeling like he was in hell as that week. If he had a gun, he would have ended his life.
We also are wondering if his dopamine receptors have been permanently damaged because he does not get the positive response that others do from Gabapentin.
Yes, Gabapentin and Horizant did not seem to work for me after getting off the DA's. I feel that mine were damaged and the research says they can be. SalemLake has a theory that taking berberine every morning could help repair those receptors-you may want to look for our exchanges on the subject. I have tried it for a few months and plan to re-start it. Just an FYI for you. What is he taking now?
Glad that combo is working-perhaps his receptors are not damaged after all? Most of us only find relief with opioids, if truly damaged by DA's-or so it seems on the forum. Or, are you saying that he is still suffering? I hope he is getting sleep now.
Omgosh-50 lbs!! I lost at least 20 lbs after getting off the DA's-so far, it is really the only bonus, as my path has been really tough and miserable. Hopefully the weight will fall off of him the way it did for me.
Fellow Canadians! I’m very sorry to hear about your husband’s experience. And ABSOLUTELY! After I developed RLS/PLMD, my daytime energy has been, seemingly, permanently zapped. I think much of it is due to the nighttime PLMD but I have gone through several, years long periods when I’ve had symptoms of near narcolepsy/cataplexy (sudden sleepiness and weakness) and have taken Gabapentin for many years so I think there’s a definite link between RLS, PLMD and Narcolepsy and/or the medications used to treat them.
My RLS/PLMD was definitely caused by an antidepressant, which are beginning to be recognized as having a greater impact on dopamine than once thought. Serotonin has a pretty direct impact on the dopamine system. 50% of people going through opioid (dopamine) withdrawal develop movement disorders. Medications used to treat narcolepsy are thought to act mainly through dopamine. The dopaminergic system should be treated like you’re driving in downtown NY - go slow no matter what people yell to you. I’m not as familiar with Gabapentin in regards to the dopamine system but as a “calming” neurotransmitter (hence it’s anti stimulant effect on RLS) I would think it wouldn’t have a negative impact on dopamine but may result in damage to the “calming” system, thereby possibly creating daytime sleepiness and similar disorders.
thank you so much for this really informative post, ircam2112. I was going to post today about my own experience of recently going back on mirapex after about 2 years off it. I came off because of severe augmentation. In that time, i thought maybe i had beat RLS with dietary measures. But i had unrelenting back pain, SI JT pain and often sciatica in one leg or the other. I rarely slept for more than 90 minutes, and never got into deep REM sleep. It took me a long time to realize that perhaps my brain was reinterpreting RLS symptoms as pain, since my symptoms followed the same time pattern as my RLS symptoms: starting 2 hours after going to sleep..lasting intensely until 4 am, and then disappearing. My ferritin levels were fine. I waited to get into a supposed "expert" on RLS, at a major medical center. I was put on lyrica which made me feel much worse. A pain specialist injected my spine. He recommended cymbalta. (Horrible!) no one believed me that it was RLS. In desperation i got out my stash of mirapex and am taking 1/2 my previous dose. From the first night, i am sleeping deeply...waking up 3x a night instead of 9. And beginning to feel like i will survive this..about a month ago, 2 detailed posts about magnesium being a dopamine antagonist led me to change when i was taking magnesium and melatonin...they were both counter-acting the mirapex. I now take them in the morning. I would agree with you...mirapex can be helpful for some of us..and in my case, knock on wood...i pray it will continue to do so. It is the ONLY medication that has helped me. A dietary strategy that has helped remarkably was also suggested on this site, sometime last fall. I can't find it at the moment. The person posted detailed information on why foods with collagen and oxalates aggravate RLS. This has been so helpful for me. I avoid meats that have been simmered...eg anything from a crockpot, or soups. Risottos give me horrible RLS. Bone broth: terrible for me. Also foods laden with oxalates or histamines. I only eat meats that are freshly prepared and i eat them immediately. Big help! There is a process for eliminating oxalate foods...please contact me for references. I won't go into detail now.
I started on pregabalin with slowly increasing dosage. Before I could get to a meaningful therapeutic dose I had the worst experience..... I was involuntarily kicking and jerking and couldn't get to sleep. It was hellish and like NOTHING I had ever experienced before. I was just trying to address severe PLMS.
I was able to substitute gabapentin to ease off of it and then go with nothing. I could myself FORTUNATE to learn of it quickly and get off before the withdrawal would have been difficult.
I strongly suspect the rate of ICD and Augmentation is FAR higher than studies report.Most people who experience these common side effects do NOT report them via the FDA or the UK yellow card reporting scheme.
As most doctors aren't taught anything about RLS, they don't recognise Augmentation either.
Most people who visit this site do so because they're experiencing Augmentation. The same on most other help groups.
There is also a growing belief that dopamine agonists cause permanent damage to dopamine receptors. In mild cases it means pregabalin and gabapentin and iron infusions don't work, in more severe cases it can cause anhedonia.
Dopamine Agonists should be reserved for cases where nothing else has worked and then, they should be rigorously monitored with drug holidays and switches to avoid over excitement of the D1 receptors.
Studies on ecopipam are underway to see if it can stop the D1 receptors being over excited by DAs.
Hi Ircam, as we discussed before, it is unlikely that you have RLS/PLMD, but rather some form of Myoclonus, since you have involuntary movements all day long while at rest. Have you tried to find a support group for Myoclonus? Augmentation may not be as much of a worry for people with your condition.
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