RLS: Have had RLS for quite sometime... - Restless Legs Syn...

Restless Legs Syndrome

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RLS

Anna51 profile image
Anna51

Have had RLS for quite sometime. It's getting worse & am getting quite depressed, as not getting a lot of sleep. I'm taking pramixople 4 times a day & finding it doesn't work as well as it use to.

37 Replies

Oh dear I am sorry to hear this.

Firstly to reassure you that what's happening to you is not at all unusual.

In addition this can be remedied. The remedy is simple but unfortunately not easy.

I can't really understand why you are taking pramipexole four times a day, this is quite unusual. Normally, since RLS usually only occurs in the evening or night, it's only taken once a day.

I'm only guessing that your reason may be that you experience symptoms during the day and not just at night.

I wonder then if that's always been the case or it's something that's developed over time.

I also wonder if yoiur symptoms were originally only in your legs, but have spread to other parts of the body.

If this is the case, or is even only partially so, then you may well be suffering from dopaminergic augmentation, which is caused by the pramipexole.

Augmentation is a major complication of pramipexole and is very common. Another, less common, complication is Impulse Control Disorder.

There are three basic things that can be done to alleviate augmentation.

1) to have blood tests for iron deficiency i.e. serum iron, transferrin and ferritin.

The guidance on this is if yourferritin is less than 75 then start on an oral iron supplement. This is the case even if the other two are normal.

Please see this link

sciencedirect.com/science/a...

2) check that there isn't something that is making your RLS worse. This could be any other medication you're taking for any other condition. The main ones are antidepressants and sedating anti-histamines, but there are many others.

It could also be any inflammatory condition.

3) the best way to treat augmentation caused by pramipexole is to stop taking the pramipexole.

This sounds simple, but can be quite hard. The benefit of doing this is that the augmentation should disappear. However your RLS would probably return to how it was before you started taking pramipexole.

It's hard because you will have developed a dependency on the pramipexole and when you try stopping it you may have severe withdrawal effects.

You must not stop taking it suddenly this is dangerous.

To minimise withdrawal effects you will need to reduce the dose slowly. This creates a bit of a complication in your case, because you're taking it four times a day.

Normally, (if you wre taking it once a day), I'd suggest you reduce the dose by no more than half a 0.125mg (0.088mg) tablet a day and no less than once every two weeks. Usually symptoms may get worse 24-48 hours after the dose reduction but should lessen again in 10-14 days.

You could still do this, but would probably have to start reducing the earlier doses first.

I'm not a doctor so can't advise on what a doctors should prescribe, but I do know that an opioid such as tramadol or codeine can help with withdrawal effects if they are very severe.

Furthermore, it might be a good idea to consider an alternative medication to pramipexole to help control your RLS symptoms, to replace the pramipexole. You can start on the alternative before reducing the pramipexole and it may help.

I'd suggest you do not let a doctor prescribe ropinirole or rotigotine to replace pramipexole. These, like pramipeole, are both dopamine agonists and augmentation is caused by all of them.

The medications recommended to replace the dopamine agonists are called alpha 2 delta ligands, i.e. pregabalin or gabapentin and, if you live in the US then gabapentin enacarbil.

I suggest you read the pinned posts about augmentation on this site and read other members posts about their expereince of augmentation and how they dealt with it.

You are not alone!

If you live in the UK, please read this link and refer your doctor to it if necessary.

cks.nice.org.uk/topics/rest...

If you don't live in the UK, then you will not be able to access this web site. Howvere here is an excerpt.

Augmentation is a major complication of dopaminergic treatment for restless legs syndrome (RLS) [Garcia-Borreguero, 2011; Garcia-Borreguero, 2013; Garcia-Borreguero, 2016].

It is a long-term consequence of treatment that may develop months or years after treatment is initiated.

Augmentation is characterized by worsening symptoms of RLS, in particular their earlier onset in the day, increased intensity, or spread to the arms or trunk.

Augmentation should be considered when any:

Maintained increase in symptom severity develops despite appropriate treatment.

Maintained increase in symptom severity develops following a dose increase, particularly if a dose reduction leads to an improvement in symptoms.

Earlier onset of symptoms that develop in the afternoon/evening.

Spreading of symptoms to previously unaffected body parts.

Shorter latency to symptom onset during the day when at rest.

Measure the person's serum ferritin. If the concentration is less than 50 to 75 micrograms/mL, investigate potential causes of iron deficiency anaemia and if appropriate offer oral iron supplements.

Ask the person about any lifestyle factors (such as sleep deprivation, alcohol use, decreased mobility) or recent medicine use (such as dopamine antagonists, antihistamines, or antidepressants), in addition to any recent opioid discontinuation or blood loss that could cause symptoms mimicking augmentation.

If there are no apparent exacerbating factors, and symptoms are severe, stop the causative drug. An option is to switch to a non-dopaminergic drug such as an alpha-2-delta ligand,

National Institute for Health and Care Excellence (2020)

Anna51 profile image
Anna51 in reply to Manerva

HiThank for your input.

As I mentioned in my original text, I've have RLS for the last 35 years. It effects me during the day & night. I don't think the premaipoxle has caused it. I get it in my arms as well. As I've got older the symptoms have got worse.

Manerva profile image
Manerva in reply to Anna51

My apologies. I don't recall reading your original text, only what you've written above.

I can only say that what you describe are the classic signs of augmentation, so sorry if I'm wrong.

If you're a happy to carry on with the pramipexole then it's no problem.

Anna51 profile image
Anna51 in reply to Manerva

HiHave been taken pramixople for the last 5 years.

My youngest daughter gets RLS too, but pleased to say it's not as bad as mine.

I'm hoping to see my GP soon & talk it over with her.

WideBody profile image
WideBody in reply to Anna51

I concur with Manerva and Pam34, this is augmentation. I have been there and I am sorry to say the way out is difficult, but you will get you life back.

I hope you find relief soon.

Pam34 profile image
Pam34 in reply to Anna51

Hi Anna

I have to agree with Manerva. This is a classic case of augmentation. I’ve been there, and after a horrendous withdrawal, came through the other side and got my life back. There are far too many people on this forum who have/are suffering from it, often through doctors/neurologists ignorance and reluctance to listen.

Just look for augmentation in the search tool. It appears far too frequently.

Pam

Joolsg profile image
Joolsg in reply to Anna51

Classic augmentation. Manerva has given excellent advice and even though he says he's not a doctor, I guarantee he knows 100% more than any doctor or neurologist I've ever come across!. Be aware that RLS is not taught at medical school or during GP training so in the UK, your GP will know nothing about augmentation or how to safely guide you through withdrawal.

Follow Manerva's advice, reduce the Pramipexole over a minimum of 3 months and find a GP who will read the info you show them.

Your RLS will continue to increase in intensity and move to other body parts until you get off it.

Rosyrestless1 profile image
Rosyrestless1 in reply to Joolsg

That last sentence made respond. RLS will continue to increase and move to other parts of the body no matter what. I haven't treated with dopamine agonists for years and I now have it in my torso and left arm during the day and at night. I use tramadol nightly, emulsified Oregano oil tablets for the gut crawling and cannabis with little relief. Still, without the tramadol I would've been admitted to an asylum by now. Oregano is great for gut crawling if you can source tablets.

Joolsg profile image
Joolsg in reply to Rosyrestless1

Rosy, are you aware Tramadol is the only opioid to cause augmentation? I suggest you ask your GP for an alternative opioid like Oxycontin, methadone or Buprenorphine.

Rosyrestless1 profile image
Rosyrestless1 in reply to Joolsg

Aware but have had no problems with tramadol for 15 years+ but am prepared to ask for something stronger if I need to. Thanks.

Joolsg profile image
Joolsg in reply to Rosyrestless1

Augmentation is a worsening of RLS, and it starting earlier and moving to other body parts like your torso and left arm. It sounds like Augmentation on Tramadol. I would monitor it in case it continues.

Good luck

Rosyrestless1 profile image
Rosyrestless1 in reply to Joolsg

I'm familiar with augmentation as I have long been off of dopamine drugs which did cause obvious augmentation. I will ask my doctor about tramadol augmentation. Mine has increased in severity with age mostly.

Yikes. Chronic sleep deprivation is a very serious issue. No wonder you feel depressed.

I've never come across someone taking pramipexole four times a day. The half life of the medication isn't that short to warrant that. When you see your GP don't undersell what's happening to you. One possible option is to see if a short course of a sleep medication can provide you with some much needed rest. If it does, and your symptoms of hallucinations and such don't lessen then I would look to other causes. Also, don't let your GP just randomly prescribe you an antidepressant when you bring up your depression(don't forget to mention it). There's a select few that in general don't make RLS worse but there are plenty that do. They should be aware of this. Do your homework before you go in. Moreover, don't be afraid to suggest that your doctor do some homework as well and research the most current trends and treatments you may need. Some just have a fixed mindset on how they treat RLS. You deserve relief. Demand it. It can seem like life and death at times, because it is, and it's very real. Keep us updated.

Anna51 profile image
Anna51 in reply to ziggypiggy

Hi

I had all the RLS symptoms, before I was prescribed pramixople, as it was getting worse before I was prescribed this medication, with exactly the same problems as I have now.

Have contacted GP, haven't heard back her yet. Does it run in families?

ziggypiggy profile image
ziggypiggy in reply to Anna51

It runs in my family and a few others I've personally known. I'm not sure if they have positively identified a gene or not. Someone on this board probably knows.I've received such good results with taking Opiods for relieving RLS. It comes with its own set of issues as well. Finding a Dr that will prescribe it. It can be addictive and dependant. Dependancy is a given but that is true with most of the medication used for RLS. You also face the real stigma of being in Opiods from family and friends even if you aren't exhibiting addiction behaviors. It becomes a risk/reward situation for you and your doctor. Your quality of life has and is in jeopardy of being disabling.

I wouldn't start out with Opiods to treat RLS, but that might change as they keep developing synthetic versions that are supposed to be less addictive. But it's definitely becoming an increasing option for severe sufferers. I would suggest you have your GP look into it as a viable option. You could even provide her with links to studies and research on the subject.

I went in to my Drs office in to tears I told her straight up if you don't fix me I will commit suicide this pain is in barrable becuz I took my self off of mirapex my sleep Dr put me on 600 mg of horizant which is gabapentin family I was still in pain my family Dr wrote me 2 of the5 /325mg if oxycodone 1 in mid day as needed and I take at night .of course I go to a pain dr he's a idiot he's like no the Horizaiant is enough. I'm like yeah they never had the pain we have suffered becuz of idiots like him prescribed us mirapex becuz it suppose to work for rls hell no it's a night mare from hell. I'm lucky my family Dr is willing to keep the oxycodone for now also

I have tried many medicines and the best I've found so far is tylesine and magnesium Resent research shows by increasing your dopamine helps alot.

Works for me.

DicCarlson profile image
DicCarlson in reply to Legs247

Did you mean tyrosine? Some additional information...

dietspotlight.com/l-tyrosine/

healthline.com/nutrition/ho...

Legs247 profile image
Legs247 in reply to DicCarlson

Yes sorry for the spelling 😅

Manerva profile image
Manerva in reply to Legs247

Great that it's working for you and there is no reason for you to stop taking it as long as it does.

A word of caution however. It's true that increasing dopamine levels can relieve RLS to a degree, but it also raises problems.

Levodopa, which does raise dopamine levels was orginally used as a treatment for RLS. The fact that it works actually was the first indication that RLS is due to a doapmine dysfunction.

The fact that RLS gets worse at night is explained by the fact that dopamine levels fall at night.

Why this happens may be explained by an analogy.

Imagine you want to throw something at a wall and you want so much of it to stick. In this case, there are only certain places it will stick. If it hits other places it won't stick.

You can't see the sticky places so you just have to throw the something at random hoping it will stick.

It seems logical that the more you throw then the more will stick. However, how much you throw is not the only factor. The other factor is that the more sticky places there are on the wall, then the more of the something will stick. Vice versa, if there are less sticky places, the less will stick.

The something is dopamine, the sticky places are dopamine receptor sites.

In RLS there is not enough dopamine sticking to the receptor sites. This usually starts in the evening when dopamine levels are at their lowest. It doesn't happen to people who don't have RLS even though their dopamine levels also fall at night.

This is because RLS is NOT due to a lack of dopamine it's due to a lack of functional receptor sites. i.e. not enough sticky places.

In this case throwing more dopamine at the sites will have some effect (the more you throw, the more sticks) but it means that dopamine levels are higher than normal. It's also been found that dopamine levels in RLS subjects are already higher than normal.

Herein lies the problem, these raised dopamine levels can cause further reductions in the number of available receptor sites (less sticky places). Furthermore there is some recent information that suggest that it increases the number of other sites, which "steal" the dopamine.

Dopamine agonists act differently, they don't directly raise dopamine levels they stimulate receptor sites. However they indirectly raise dopamine levels and can also cause a loss of functional receptor sites. The ultimate result is augmentation.

Hence although anything that raises dopamine levels may intially affect RLS symptoms, if they raise them significanlty for any period of time it may result in augmentation.

I have heard that mucuna pruriens (velvet beans) can raise dopamine levels, but can cause augmentation.

I'm not sure either way if tyrosine supplements raises dopamine levels. Tyrosine is a precursor of dopamine it's true, but whether more tyrosine results in more dopamine isn't entirely clear. It still has to be converted into dopamine.

You don't build a house by simply throwing a lot of bricks on the ground, you need a bricklayer.

In any event tyrosine is an amino acid and is available in sufficient quantities in a normal diet.

Just some thoughts, if you find tyrosine helps you then it does, whatever the theory.

o

DicCarlson profile image
DicCarlson in reply to Manerva

Most supplements are 500mg of tyrosine - yet a 6oz serving of steak contains 2100mg - so, dietary choices might be a better choice...

myfooddata.com/articles/hig...

Manerva profile image
Manerva in reply to DicCarlson

Exactly. Not that I ever eat meat, being vegetarian, (but not vegan).

However, the name tyrosine comes from the greek tyros = cheese.

Legs247 profile image
Legs247 in reply to Manerva

Thank you for that, very useful. I will continue to research and use myself as a guinea-pig.

Manerva profile image
Manerva in reply to Legs247

Great! Let us know how you get on please. That would be very helpful.

Legs247 profile image
Legs247 in reply to Manerva

I will.Bye the way I also take magnesium and iron.

Manerva profile image
Manerva in reply to Legs247

That's great, iron particularly.

I find mucuna to be occasionally helpful but as you say augmentation will happen with continual use. The most effective treatment in the end has been opiods and weirdly oregano oil tablets to calm SIBO and RLS in the torso caused by the same. Low fodmap diets can also relieve gut symptoms and overall strength of symptoms.

River58 profile image
River58 in reply to Manerva

Minerva schreef: "Dit komt omdat RLS niet te verbeteren is aan een gebrek aan dopamine, maar aan een gebrek aan functionele receptorplaatsen, dwz niet genoeg plakkerige plaatsen." Dit hechtinsprobleem is een nieuwe kijk voor mij. Is dit de reden waarom SSRI's slecht zijn voor rls omdat ze de gevoeligheid van serorotonine en dopaminereceptoren verminderen? Propinirol (Wellbury) zou voordelen voor rls moeten bieden, maar volgens deze kleverige theorie zal dit medicijn het ook erger maken. Heb ik gelijk? Met dank aan Manerva.

Manerva profile image
Manerva in reply to River58

RLS is very complex and the deeper you look at it, the more complicated it gets. I don't look at it to deeply but what I've read so far it is well accepted that most antidepressants make RLS worse. This is not just SSRIs but most others as well.

The only exceptions appear to be "sedating" antidepressants Trazadone and Nefazadone and also buproprion.

I don't think it's exactly clear why. I believe as regards SSRIs

one theory is that because the conversion of amino acid into dopamine and the conversion of amino acid into serotonin both require the same enzyme. If anything raises serotonin levels then that requires more of the enzyme leaving less to make Dopamine.

SSRIs do, in effect, raise serotonin levels.

Although dopamine levels are either normal or actually raised with RLS, it is insufficient because of the lack of receptor sites, (sticky places). Hence if dopamine levels are actually lowered it make things worse.

Apologies, I have not understood your reference to "proprinirol" and "wellbury".

Wellbury might refer to wellbutrin, alias buproprion the antidepressant.

Proprinirol could either be ropinirole the dopamine agonist or propranalol the beta blocker.

The problem with treating RLS with levodopa which raises dopamine levels or with dopamine agonists which stimulate the "D2" receptor sites is that these "downregulate" the receptor sites, so there's even less.

Recently it's also thought that "D1" receptor sites are increased which then steal the dopamine.

I hope this answers your questions.

I'm afraid I don't understand Dutch.

River58 profile image
River58 in reply to Manerva

Thanks for yourcanswer. yes a agree, its very complicated, but i hope at one day we will inderstand the mechanism of rls Minerva. It's so worth keep on trying!.Iam sorry, i ment Bupropuon Wellbutrin. The principle of ssri is to gain serotonoe levels by making the reuptake receptors (and dopamine receptors) les sensitive. (inhibit reuptake ensures that more serotonine is longer available)I think SSRI and also Wellbutrin unfortunedly make other receptors les sensitive.as well.! (read les sticky) That confirmed your theory of short on dopamine caused by bad receptor functionallity. The qestion is why are the dopaminic receptors functioning so badly, even by jounger people. My RLS has occured half a year after starting esciilotapram 10mg. Changing from escilotapram to Wellbutrin had no effect at alll. I stopped both AD but RLS is still there every night. I tried Ropinirol 0.25 andc0.50mg but after few weeks the effect was already gone. Now i concider to start Gabapentine 2 x 100mg a day or suffering withouth any medicine. 😕

LotteM profile image
LotteM in reply to River58

Hi River, your story sounds somewhat like Manerva's, as I recall he also got (intensified?) RLS after having been started on an antidepressant. Goven your precious reply and discussion about receptors, it may nit have been wise to resort to a dopamine agonist like ropinirole. Maybe an alpha2delta ligand like gabapentin would be better for you. Manerva controls his RLS quite well (I believe) with gabapentin. I am sure he will reply again and give more details.

PS. Are you from The Netherlands? I am.

Manerva profile image
Manerva in reply to River58

A major cause of RLS is Brain Iron Deficiency (BID) due to a limited ability for people with RLS to transport iron across the blood brain barrier.

This is what leads to the neurotransmitter dysfunction in RLS, i.e. mainly dopamine and glutamate.

Hence iron therapy can treat the cause of RLS, rather than just treating symptoms.

RLS medications only treat symptoms.

Here's a link to some information about this.

sciencedirect.com/science/a...

Managing RLS is also not just about doing things to treat symptoms but also about avoiding things that make them worse. These are triggers or exacerbating factors.

Everyday triggers include things like alcohol, sugar and for some, caffeine.

There is quite a long list of drugs which make RLS worse, the main ones being antidepressants and sedating antihistamines.

Inflammation is a mediating factor in RLS and if you have any known inflammatory conditon or even sub-clinical inflammation yournot awzre of, this can be a factor.

Diet therefore can be a factor, generally a diet low in carbohydrates can help, for some a low oxalate diet, gluten free, lactose free or anti-inflammatory. This a matter of trial and error.

Ropinirole, a dopamine agonist (DA) like all DAs is usually very effective in controlling symptoms. All DAs suffer from the same problem of "loss of efficacy". This can occur within months, but usually takes years. If yhe response to this is to increase the dose this can lead to dopaminergic augmentation, which is very serious.

Because of this DAs are no longer recommended for RLS. The alternative is an alpha 2 delta ligand, gabapentin or pregabalin.

pubmed.ncbi.nlm.nih.gov/274...

River58 profile image
River58 in reply to Manerva

I have read your answers over and over again and I fully agree. It is well summarized. I read also some other post of you Manerva, and they are all very complete and clear answered. But i have stil a lot of questions to ask and things i'm wondering about. Perhaps i wil ask them another time in another treat 😩. Wish you agood nigh

Manerva profile image
Manerva in reply to River58

Feel free to ask any questions you may have. Somebody will usually try to answer them.

I had a blood test about 3 weeks ago. My iron levels are normal, but my vitamin D was very low. I take medication now.

Manerva profile image
Manerva in reply to Anna51

To be told your iron levels are "normal" for somebody with RLS is not helpful. Ideally with RLS your ferritin level should be at least 200.

Anything above 12 is considered "normal".

If your ferritin is less than 75 then it's recommended that you take an oral iron supplement.

See this link.

sciencedirect.com/science/a...

Sorry to that.. I have it at times..depends on what i get done.. gabapentin seems to help some..

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