Dopamine Agonists, Augmentation and Resetting RLS – What to Expect?

[frickets]

Hello. My 20+ year battle with RLS and using dopamine agonists (DAs) has led to augmentation. After a couple years of failed attempts to get off DAs, I think I’m ready to kick the addiction and reset.

Until a few years ago Pramipexole was sufficient. As I’ve read so many times in this forum, my primary care had no issue increasing my dosage over the years as my symptoms worsened – led me right into augmentation. After a few false starts over the past couple years trying a variety of doctors and replacement medications that didn’t work, I found someone I have confidence in. We’ve worked in Methadone and my sleep is better, though my daytime/evening symptoms have continued – in fact, worsening over the past year. We’re also looking into the possibility of adding iron infusions.

I don’t think I can go cold-turkey (~2 weeks). I am a caregiver for my wife and afraid of being debilitated. So, we’re planning to slow roll it (~1 month). I’ve started to taper off Pramipexole while slowly increasing Methadone to compensate. Fingers crossed! I’m both excited about the potential for better days, and a bit scared of the process. Can anyone shed light on what I may have to look forward to? Can you share your experience with getting off DAs? Can you recommend any tips and tricks for dealing with withdrawal? Thanks in advance.

[Polar Bear]

Well done on facing the challenge of weaning off your pramipexole. You speak of addicition, I prefer to think of it as dependancy. An addicition often means taking more of a drug to seek a 'high' whereas dependency is the need of a drug in order to obtain relief. You plan on weaning off your DA/pramipexole over about one month.
Having previously failed twice, I then did it very slowly, taking 10 months to wean off ropinerole which is a sister drug to pramiipexole. This was supported by using Cocolamol 30/500 (a low end opioid) and Pregabalin. Weaning as slowly as I did (and with the supporting meds) meant I had virtually no issues in eventually stopping the DA. No bad side effects whatsoever. When reaching the end of discontinuation I was very careful to make the reductions smaller the nearer I got to finishing.

People may differ greatly in their journey through augmentation and weaning off a DA. Some people just want to get off the drug as quickly as possible. Be careful not to come off too quickly, but you appear to be sensible in your plan.
During the first few days after stopping the dopamine medication, RLS symptoms may be extremely severe and the patient may have reduced sleep, probably actually no sleep. Perhaps difficulty even remaining seated for any length of time.
Improvement in symptoms hopefully could happen by day 5 or 6. The degree of withdrawal symptoms and time to recovery between dosage decreases varies widely among individuals.

[Rustsmith]

You didn't mention what dose of pramipexole you were taking, so I cannot be too specific with suggestions beyond telling you of my experience getting off of pramipexole with methadone. I was also taking 900mg gabapentin then (and continue to take that dose today).

I was taking between 0.75mg and 1mg/day of pramipexole when I finally was able to start the changeover. My wife and I were in the midst of an interstate move when my neurologist told me that I needed to switch. He wouldn't start the transition and told me to wait until I had a new doctor. That was good because it took four months to get an appointment. Fortunately, my new doctor agreed to switch me from pramipexole to methadone immediately.

As I remember, I cut to 0.25mg pramipexole and 0.5mg methadone for the first week with instructions to go to no pramipexole and 10mg methadone the following week. I did cut out the pramipexole by it only took 2 days for me to realize that 10mg methadone was too much. I cut myself back to 5mg and sent a message alerting my doctor to my decision, which she endorsed.

I stayed on 5mg methadone for the next year, but started having sexual problems and depression. Initially my doctor blamed the gabapentin and cut me back to 600 mg. My sleep got worse and the problems didn't resolve, so we went back up to 900mg. I asked to switch to tramadol ER with the idea that it might help with the depression. The tramadol helped with my depression (it is also an anti-depressant), but made the sex issues worse, so we started switching between methadone and tramadol every six months for the next few years.

That continued until I learned that all opioids, especially methadone, depress testosterone production in men (but not women) and that low T was causing both of the side effects that my doctor blamed on methadone. She should have known better, but didn't. I started hormone replacement therapy and have felt wonderful ever since.

The only other side effect to warn you about is one that patients often call "alerting". Opioids are supposed to be sedatives but can cause RLS patients to become very wide awake, much like caffeine for others. Not everyone has this happen, but I have found that methadone causes me to become alert and makes falling asleep impossible for about 10 hrs after I take it. Since methadone is a 1/day pill, the solution was simple. I take my pill at lunchtime. On the days that I forget and don't take my pill until mid-afternoon when I start to feel the initial symptoms of methadone withdrawal (sweaty and flu-like), I cannot fall asleep that night until midnight but feel fine after about 20 minutes.

[frickets]

Thank you for your responses. The support extended from others who have endured similar experiences goes a long way toward helping me maintain momentum. Everyone reacts differently to various medications and treatment plans. I’ve been on Methadone for a while and find it extremely helpful. I’m 7 days into a 30-day plan to slowly reduce pramipexole and hopefully resolve augmentation issues. Almost immediately the already distressing symptoms quickly became worse. I’m trying various methods for riding out the tough times – e.g., laps around the house, taking hot showers, DIY projects. Anything that distracts my mind while giving my limbs something to do. So far the Methadone does help me get a few hours of broken sleep at night, but still not enough. I’m not sure what to expect over the coming weeks. Does it get worse? How should I prepare? I’m hoping to hear tactics others found helpful. Otherwise, I can only embrace the suck and focus on the goal one day at a time.

[Rustsmith]

I hope that you start to do better very soon. Generally, the worst time when tapering off of a DA is the last step. The other thing to consider is whether your methadone dose is enough at this point. I started out at 5mg with instructions to go to 10 (which apparently is the normal recommendation). Ten was too much for me but others have required even more to gain control of their RLS.

One side effect of methadone that I forgot to mention is that for men, it tends to depress the production of testosterone. I knew that my libido was depressed, but I didn't worry about it too much because my wife is also disabled so the reduced libido wasn't a major deal breaker for methadone if it controlled my RLS. What did become a major problem was that the low T also caused me to become severely depressed. It got so bad that I was near suicide for two weeks and wouldn't have survived if not for my love for my wife and the concern of how she would survive without me there to provide care for her. My doctor didn't seem to know what to do, but did make a change that helped me in the short term. I was the one that had to learn about the interaction between methadone and low T and the symptoms of low T. I have been on hormone replacement therapy for several years now and my only problem occurs on days when I forget to take my methadone on time (like today - URRGGH!)

[DontLikeRLS]

Hi,

This is a bit late. I'm just sharing my experience. I weaned myself off of 0.5mg of Pramipexole in Jan 2025. I had been taking it for about 10 years, and for the last two years my RLS was getting worse. I now had symptoms starting in the early evening, and they had spread to my arms. I had not heard of augmentation. I thought the disease was getting worse. I had no idea the drug was making my symptoms worse. I was up one to three times at night with RLS symptoms and a stuffy nose. The stuffy nose alone would have made sleep impossible. I would be up about an hour waiting for my RLS symptoms to lift, and for my nose to unstuff (my nose would get stuffy when I was horizontal, but slowly cleared up when sitting or standing). It was often the stuffy nose that kept me up the longest. I've had a stuffy nose at night for most of my life, but for some reason, it had become much worse over the last several years. It never occurred to me that it could be related to the Pramipexole. My sleep varied a great deal, but at times it was only a couple of hours. Four hours was quite common.

I initially tried splitting the Pramipexole dose, taking half 2 hours before bedtime (2:00AM) and the other half earlier in the evening. I was not trying to taper off at that time. I had read that splitting the dose might relieve my symptoms. It didn't. I then began the taper. I went to 0.25mg for a week, followed by 0.125mg for a week. I was sleeping a lot less, but it was tolerable, and I was able to take short naps, which really helped. I then cut the dose to zero, and things went from tolerable to dreadful. I was still getting some sleep; perhaps an hour a night, not much more. I could sometimes nap, but they were very short and infrequent. I could only nap lying on the couch with the TV on. I really began to deteriorate mentally. I was not functioning well, and was a danger to myself. I was walking into walls (had to repair the damage to one) and doing all kinds of weird things. I tried to drink a bottle of supplement tablets and poured a bottle of coke into my hand. I would find myself doing things with no idea why I was doing them, or how I came to be doing them. There were short gaps in consciousness.

I did the taper on my own, without consulting my doctor. I knew that opiates were being used to treat RLS. I had a bottle of 30mg codeine that I planned to try after my taper, and then consult my doctor. My doctor had previously prescribed these for my RLS, although he is opposed to the use of opiates for RLS treatment. I had previously tried the codeine along with the Pramipexole, but it did very little for me, which came as a surprise. I tried the codeine during the last stage of my taper, and it again made very little difference. Fortunately, I found "The Appropriate Use of Opioids in the Treatment of RLS" published by the Mayo Clinic. I discovered that "pretreatment of RLS with a dopamine agonist will negate any benefits of opioids", and a 10 day washout period was required before substituting an opioid. I tried the codeine after the 10 day washout. It works. I have a referral to a movement disorder clinic, and will pursue the meds further at that time.

I am so glad to be off Pramipexole. RLS symptoms no longer occur in the evening, and are limited to my legs. As an unexpected bonus, my stuffy nose has improved immensely. It no longer disturbs my sleep. I did some research and found that stuffy nose is an uncommon side effect of Pramipexole. Codeine is not perfect. I take 60mg an hour before bedtime, and another 60mg when symptoms wake me up in the middle of the night. (I only take the second dose when at least 3.75 hours has passed since the first dose. I will wait or go back to bed if insufficient time has passed.) It then takes close to an hour before I can get back to sleep. But at least I can finally get a total of 8+ hours sleep. I feel and function much better during the day.

[frickets]

Thanks for the note. It’s been a while since my original post and last update. I’m doing ok now but still have some work to do. I was fortunate to find a Neurologist who specialized in movement disorders. I can’t stress enough how important I think it is for RLS patients to be treated by a neurologist. My sleep doctor and PCP are soaking up my experiences. They say it’s so they can better support other patients. I think they continue to misunderstand the extremes of this disorder and should be referring their patients.

It hasn’t been easy. At the start of my detox, I was on 15MG methadone and 1MG pramipexole per day (0.25MG four times a day). This dose of pramipexole was already down considerably from the 2MG+/day dosing I had been on before my first attempt to detox. To start this time, we reduced daily pramipexole 0.25MG a week. My RLS symptoms immediately escalated 24 hours a day – often extremely bad – walking, jumping, shaking arms and legs violently to the point of being sore the following day. My sleep dropped quickly – only getting 1-3 hours a night and always in broken segments. I saved projects from around the house for the bad hours – e.g., replacing a light fixture, rotating tires, learning guitar – anything that required physical activity and cognitive focus. This helped forget the terrible symptoms and pass the hours and days. I wish I had queued up more projects ahead of time.

Two weeks in we increased methadone to 20MG but it did nothing to improve my symptoms or sleep. Although my labs were “normal”, at three weeks in I received an iron infusion and was told not to expect any improvements for several weeks. I cooked and ate very often as it helped distract me, and I gained 10 pounds. My memory and cognitive skills deteriorated. It was horrible! I stopped driving more than 10-15 minute trips, and not at all in the afternoon or evenings as the probability of falling asleep at the wheel was almost certain. I often caught myself starting to fall asleep while standing and tried to avoid positioning around anything that might cause injury like tables or countertops. Once completely off pramipexole it got even worse. I eventually did fall asleep while standing – landing on the back of a couch I was standing behind watching TV – knocked my breath out. Eight weeks in I gained no improvement in RLS or sleep from the methadone, iron infusion or suspending pramipexole.

With my system free of pramipexole for over a month I met with my doctor. After considerable discussion we opted to stop 20MG methadone and start buprenorphine/nalox – starting at 1MG daily. These were the worst days – sometimes not sleeping at all. We slowly increased buprenorphine up to 3MG daily, but then started to run into central sleep apnea (CSA) issues and we had to back off. A condition further complicated from living above 5000’ altitude. I was desperate, and we weren’t exactly sure which direction to go. Through my research on this forum I had read about others who had success reintroducing low-dose pramipexole, so I did. OH MY GOD! I slept. Just 0.25MG and I got 8 hours of sleep. My doctor said, “We should only consider that in extreme circumstances.” To which I replied “You haven’t been listening. I am at wits end now!” We compromised – I would continue with the 0.25MG daily dose and work with my sleep doctor to finesse my CPAP settings and get the CSA under control.

Now, it’s been another two months and I’m sleeping great! The CSA is in check, and we’ve started again to slowly bump up buprenorphine and slowly, very slowly reduce pramipexole – hopefully to zero. My one big regret so far is I wish I had just stopped pramipexole cold-turkey to reset. A week or two of total misery would be a whole lot better than the 2 months it took to do it slowly. Though, I don’t really know if it would be better.

So that’s where I am at the moment. Sleeping well, functioning normally, and still working out pramipexole because we believe it will eventually fail me again. Stay tuned. RLS PSA: I you haven’t already, find a good neurologist.

[DontLikeRLS]

Interesting. You restarted Pramipexole. Others on this board have also done that in low dose. Unless a neurologist strongly recommends it, I won't touch it. Even then, it would make me nervous. I have a referral, but won't be able to see a neurologist for six or more months. I have a "meet and greet" scheduled with a new doctor on Feb 21. I'm looking for a doctor who supports the use on opiates in the treatment of RLS. My current doctor does not.

Glad to hear I'm not the only one playing guitar in the middle of the night. I really need the practice.

Regards,

[badnights]

@frickets, glad you're finally coming out the other side.

My one big regret so far is I wish I had just stopped pramipexole cold-turkey to reset. A week or two of total misery would be a whole lot better than the 2 months it took to do it slowly. Though, I don’t really know if it would be better.

There is only one reason to taper instead of go cold turkey, and that's to help avoid DAWS. The biggest risk factors for DAWS (dopamine agonist withdrawal syndrome) are a high initial dose of DA (in the realm of at least 10 mg ropinirole or 5 mg pramipexole) and experience of impulse control disorder caused by the DA.

At one point there was talk of DAWS being more likely after fast withdrawals as opposed to tapered withdrawals but I don't think there was good evidence for that? - others, please correct me if you know differently. I would always advise, unless your DA dose was Parkinson's-level high or unless you had an impulse control disorder, to stop cold turkey, for exactly the reason you state. The level of misery is no better during a taper, and it lasts that much longer.

That said, some people (polar bear for one) managed to taper with relatively little misery. Depends on each person, as always.

Good luck with the rest of your journey.