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What EXACTLY is “Augmentation”. The d... - Restless Legs Syn...
What EXACTLY is “Augmentation”. The definition of the root is “increase”. So, as I’m trying to understand it, it’s “bad” increasing Meds?
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Midnight-Blue
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In RLS terms , augmentation applies particularly to Dopamine Agonist medications. It relates to the efficacy of the medicine becoming less , and the RLS actually getting worse, and all over the body- particularly arms and legs.Many doctors advise increasing the medicine, which is actually the worst possible course of action.
Changing to another DA will only repeat the process.
The only course of action is to get off the DA and try new medications ( Alpha2 ligands) usually.
As Madlegs says, augmentation in relation to RLS is increasing symptoms. Hence a bad thing.
"Dopaminergic augmentation" is a complication of using dopaminergic drugs, i.e. levodopa or the dopamine agonists.
The term augmentation is also used in broader terms to mean any increase in RLS symptoms, it seems.
So there are many sources that say alternative drugs for RLS cannot cause augmentation. However some sources say that alpha 2 delta ligands can cause augmentation.
At this moment in time, it's still thought that the risk of dopaminergic augmentation is much higher than the risk, of augmentation from a ligand.
In addition whereas there are some possible explanations for dopaminergic augmentation, I've never come across any explanation for a ligand causing augmentation.
Another drug claimed to cause augmentation is tramadol. Again there appears to be no explanation for this. No other opioid is claimed to cause it.
Some sources say that rather than augmentation, tramadol causes "rebound" and this can be remedied by taking a long acting form.
Rebound is rarely mentioned in this forum. Perhaps a reason for this is that it may be mistaken for augmentation. This is possibly a reason it's claimed ligands cause augmentation.
It's a little confusing, but overall it's not clear whether drugs other than dopaminergic ones can cause augmentation.
However there's ample evidence that dopaminergic drugs definitely cause dopaminergic augmentation and the risk is high.
Noddedoffagain in reply to
Oh dear - I have been prescribed Tramadol after coming off the Neupro patch. It is easing some of my painful knees and I’m getting some sleep. What is ‘ long term Tramadol please?
in reply to Noddedoffagain
Not "long term" but "long acting" this is where the drug is manufactured in such a way that it is released over a longer time period usually 12 to 24 hours.
Sometimes this is called extended or prolonged release.
This is in contrast to "immediate release" forms
The medicine I take is immediate release, it is fully absorbed, hence reaching a maximum level, in about 2 - 3 hours, but about 6 hours after that, half of it has gone, after 12 hours 3/4 gone.
The first dose of an extended release drug can take about 6 hours to reach maximum, but after that, it can stay more or less at maximum for 12 or 24 hours. Then you take the next dose.
Rebound occurs because the level of the drug falls, with a "long acting" drug, this doesn't happen, (theoreically anyway).
Noddedoffagain in reply to
Thank you again for sharing your in-depth knowledge x
in reply to Noddedoffagain
A further point is that although weaker opioids like tramadol or codeine are useful in combination with a RLS medication e.g. an agonist or for helping wean off an agonist, they're not really ideal as a sole long term (meaning for years) treatment for RLS. It is recommended to use a low dose of a potent opioid, oxycodone, methadone ir buprenorphine.
Noddedoffagain in reply to
Many thanks Manerva. I’ve noted those & will suggest one of them when I see the sleep consultant next, as a follow up to the iron infusion that I had last month
Wondering why you came off the Neupro patch? I’ve been on 2mg for a few days now and it’s working.
I had already augmented on Mirapexin so I was then prescribed the Neupro patch. From what I have learnt from this site it was not the correct thing to do. Last year I augmented and had a dreadful time weaning myself off the drug. Now my only medication is one Tramadol 50gm taken before bedtime. I still get RLS but am managing it much better. Long may it last.
in reply to cmccmccmc
Most people come off dopamine agonists like rotigotine (neupro), because they've suffered one of the major complications these drugs can cause. These are Impulse Control Disorder and augmentation.
It's usually augmentation, because this is most common, very common in fact.
This is a very serious, life changing condition and that's what Midnight-Blues's post was originally about.
It seems likely that Noddedoffagain came off neupro because of augnentation then.
If you only started on the patch a few days ago, I'm sorry to say that the doctor who prescribed you this is in the long term, is not really helping you.
Apologies, if I'm wrong but as you are asking why somebody should come off the patch, I'm guessing that neupro is the first medicine you've tried for RLS. Certainly I imagine it's the first dopamine agonist (DA) you've tried. The others are called pramipexole or ropinirole.
If I'm right, your doctor is not up to date with the latest recommendations for the management of RLS.
The seductive thing about the DAs is that can be very effective and effective immediately. This may seem miraculous. The first time ever I took a DA, my symptoms completely disappeared. The very first night.
However, it may not last and augmentation can occur after some years, for some, it happens in months.
For this reason, DAs are no longer recommended as the first pharmaceutical treatment for RLS.
See this link
pubmed.ncbi.nlm.nih.gov/274...
Furthermore, the first treatment for RLS that should be considered before, or as well as medicines is iron therapy.
With appropriate and sufficient iron therapy many people can eliminate the need for drugs.
I hope therefore that your doctor carried out blood tests for iron deficiency and told you the results. When I say results, I mean the values. Being told they're "OK" or "normal" is not at all helpful if you have RLS.
See this link
sciencedirect.com/science/a...
In addition, your doctor should have duscussed with you, NOT, just what might make your symptoms better but also what might be making them worse. There are a lot of things that can make RLS, a lot! Avoiding them, if possible can improve RLS symptoms.
In my case my severe RLS was precipitated by an antidepressant. I now believe that if the neurologist who diagnosed my RLS had known this, I would never have been prescribed a DA without any warning of its complications. I wouldn't have suffered the consequences of this as I did, for years!
Whatever you do, I strongly suggest that you find out as much as you can about DAs and their complications. There is information on this site.
It's up to you, but if neupro is the first medicine you've taken for RLS. You have some options.
One is to carry on using the patch as long as it works and never increase the dose even when it starts to fail. If you were to do this, you will most likely suffer augmentation after increasing it.
Another option is to carry on using the patch, but be aware of what the signs of augmentation are. At the slightest sign of it, come off the neupro.
You really do need to avoid augmentation. First, it's horrendous! Second, it can cause permanent damage.
Most of what I've written above is based on facts.
However my own personal opinion is that you ought to go back to your doctor and tell them you don't want to take neupro. Ask for the recommended alternatives. If they ask why, tell them what zI've wriiten abiut here. Show them the links I've given you.
Ask about blood tests for serum iron, transferrin saturation, ferritin, magnesium, vitamin B12/folate and vitamin D.
But is augmentation a worsening of the condition or a case of less effectiveness of the medication.
If you state an increased need for sleep-aid medication, what you're likely to get thrown back at you is: Where's it going to end? Are you just going to take an ever-increasing number of pills?
Sleeping pills are allosteric (activators) – they attach to the side of the GABA receptor and increase GABA passing through the receptor; ropinirole is maybe an orthosteric agonist (in dopamine sites). Is this relevant to anything?
When sleeping pills have not been taken for a while, the GABA receptor site is said to be naïve, and the drug is more effective. Is this the case with dopamine agonists, or is it that once the damage is done, it's done?
Apart from problems with sedation and motoring/driving etc, why does the medical profession worry so much more with levels of medication applied to the GABA receptors, than it seems to with levels of medication applied to the dopamine receptors?
It's a worsening. Many experts believe exposure to DAs permanently damages the dopamine receptors so going back on them will inevitably lead to augmentation.However, there do seem to be some who have gone back to a very low dose DA after augmentation and it has helped. With this disease it really isn't a 'one size fits all' approach.
in reply to ironbrain
"Loss of efficacy", (less effectiveness), is perhaps better considered as a separate issue. Some drugs do lose efficacy, but don't cause augmentation. Sleeping aids are an example of this.
When loss of efficacy occurs, symptoms may return to how things were before starting taking the drug.
RLS augmentation is a significant worsening of symptoms caused by the drug, i.e. considerably worse than they were before starting the drug. In addition, if the drug is reduced or stopped then the augmentation improves.
If this were merely loss of efficacy then this improvement wouldn't happen.
Augmentation is usually mentioned in relation to "dopaminergic augmentation" , to give it its full name.
In this case it is caused by taking either Levodopa or a dopamine agonist.. Both of these can result in just loss of efficacy, but usually this is a precursor of augmentation. If somebody suffers loss of efficacy and the drug dose is increased to counteract this, then this can precipitate augmentation.
Sleeping aids do NOT cause augmentation.
There are many types of sleeping aid and for many of these there is the phenomenon of "tolerance" i.e. after a while a given dose loses efficacy and the dose has to be increased. If nothing else this means that you become "dependent" on the drug.
That in itself may not be a problem unless either a) the drug has long term harmful effects or b) you want to withdraw from the drug.
However, tolerance also increases the risk of addiction, and many sleeping aids are often classed as addictive and harmful.
What you get "thrown back at you" is thus, probably justified in relation to sleeping aids.
It's worth pointing out that sleeping aids are not a treatment for RLS. They may help to some extent if insomnia is a strong element of RLS, but they don't treat the RLS itself and insomnia is a feature of RLS, (hyperarousal).
Any discussion of allosteric or orthostatic is really a distraction at least if not entirely irrelevant.
Dopamine agonists are just that, agonists. They stimulate dopamine receptors sites thus increasing the activity of dopaminergic neurons.
They work because RLS is partly due to a lack of D2 dopamine receptor sites and stimulating the reduced number of sites available can improve symptoms. However the long term effect of them is to even further reduce the number of sites available and also possibly increase the number of D1 receptor sites, which compete for dopamine. This causes the RLS to get worse - augmentation.
The other drugs used for RLS specifically are the alpha 2 delta ligands, gabapentin or pregabalin. These have soime similarities to sleeping aids, but aren't entirely the same. They can boost GABA activity and inhibit glutamate activity.
They work for RLS because RLS is also partly due to a GABA-glutamate imbalance, an excess of glutamate. They can help with sleep, but are also effective for RLS symptoms. They were originally used as an anti-convulsant or for nerve pain however, not as a sleeping aid.
They carry a signficanlty less risk of augmentation, and if augmentation occurs, it is not really dopaminergic.
Naive means that the nervous system has never been exposed to any of these agents before. For some drugs, once the drug has been withdrawn then the nervous system may return to how it was before the drug was taken, Thus it becomes "naive" again.
Thus the overall effectiveness of some drugs can be prolonged by stopping and starting again. How practical this is in the case of RLS drugs (i.e. either dopamine agonists or ligands) is dubious. Certainly for agonists.
This is because once dependent on an agonist it can take quite a long time to withdraw from them, during which time, symptoms may become worse because of withdrawal effects. Once these settle, RLS will return to how it was before taking the drug, until you start taking again. Some people do this calling it a dopamine holiday, but it doesn't seem very satisfactory to me, you might spend more time expereincing symptoms than not.
The key issue with dopamine agonists is augmentation. It's possible that after stopping a agonist the brain will return to a naive state and you can usually expect this to happen to some extent. However, there is some evidence that follwing augmentation there is permanent damage and in cases this means that other drugs, e.g. ligands which might otherwise have worked aren't effective.
This is why dopamine agonists are no longer recommended as the first treatment for RLS becasue of the high risk of augmenmtation (and the risk of ICD), Ligands are recommended first. If they don't work, the agonists could be considered, but tbis is better than the other way round.
Why do doctors worry etc
Most sleeping aids are addictive and after a while, even if the dose isn't increased are no longer effective. They are merely being taken to prevent withdrawal effects because of dependency. As well as the problem of tolerance and withdrawals, Their psychoactive properties also render them likely to cause addiction. That's the worry
.
In comparison dopamine agonists, although dependency forming aren't classed as addictive.. You don't get a high from them.
However, agonists are harmful in other ways, these being the augmentation and Impulse Control Disorder they cause. The problem is that an awful lot of doctors aren't aware of these problems. The last doctor I mentioned augmentation to didn't have a clue what I was talking about.
ironbrain in reply to
Thank you, for your replies, and for your extensive exposition, Minerva,.
I was particularly interested in your description of what causes the augmentation, the increase in D1 sites and decrease of D2 sites, etc. Perhaps, hopefully, further research in this region will lead to an understanding of how RLS develops.
Gabapentin doesn't work at all for me, so it's DAs or looking at addictive opioids/opiates.
Unfortunately, I felt you were "falling in line" a bit with regard to sleeping aids more than giving a critical assessment – probably you don't have so much experience with them as RLS treatments. I can agree there's probably a tolerance effect (but which in the newer drugs is not great enough to render them essentially ineffective). There's also the fact that once on them, one can tend to allow oneself to become exposed to greater social stress, which of course then impacts negatively on the sleep one gets. Of course, one cannot live properly without sleep, and so in that sense a dependency can (and does) develop. However, I'm not at all convinced that they (zopiclone anyway) are pharmacologically addictive. Firstly, one doesn't crave them other than to get some sleep at night. Secondly, there's little, if any, withdrawal. I can stop taking them with no withdrawal symptoms and have the best night I've had for ages (although ultimately, and usually sooner, an unsatisfactory sleep situation resumes).
in reply to ironbrain
It's becoming fairly well accepted that RLS is a genetic disorder. Recently some evidence has emerged that even "secondary" RLS requires a genetic susceptability.
You are correct, I have very little experience with sleep aids.
I only go off what I've read about them and what doctors have told me. That's based, I guess on statistics. There's no predicting how any single individual will react.
They're not recommended for RLS unless insomnia is a particular feature.
I have been prescribed clonazepam, zopiclone and more recently diazepam. I was allowed to only take the clonazepam for 28 days and was only allowed 10 zopiclone and 10 diazepam.
My individual experience is that none of them had any observable effect whatsoever. But that's just me.
However, I do believe doctors aren't sufficiently informed about the dangers of DAs. I don't believe they should prescribe them for RLS at all, except under exceptional circumstances and by a specialist.
According to the top RLS experts in the USA, augmentation is caused by the D1 dopamine receptors. Dopamine Agonists target the D3 receptors and the D1 receptors then have a tantrum because they're not getting their dopamine 'hit' so become 'over excited'. This then causes a severe worsening of the RLS symptoms. They increase in intensity, start earlier and move to other body parts.The Holy Grail of RLS research is to find a way to stop this happening. Ecopipam is being looked at and there's a researcher in North Carolina also working on a 'drug' to stop the DAs causing augmentation.
Whilst agreeing with the excellent replies above. I have heard the term ‘augmentation’ used to describe where a persons body has adapted to a drug and is so used to it that a stronger dose is needed to get the same desired effect. Therefore the dose is raised or augmented. The problem being that this can only be done before the amount of the drug becomes dangerous or ineffective. I found this with morphine, where the GP kept on increasing the dose over 15 years until on 120 mg as well as Tramadol, Codiene and Duluxotine. The side effects of theses drugs was as bad, or worse, than the conditions they were treating! For me personally Buprenorphine patches allowed me to come off them all.
in reply to Paganpatrick
The phenomenon you're referring is actually called "tolerance", i.e. when you get used to a medicine, so it no longer has the same effect. It needs more.
When a dose is increased to overcome the tolerance, this isn't called augmentation, it's just a dose increase. This can lead to an ever escalating dose and addiction.
The usual meaning of augmentation in relation to medicines is where two medicines are combined, because it's been found that the second "augments" the effect of the first, i.e. increases it e.g. paracetamol and codeine.
The meaning of augmentation in relation to RLS is a completely different idea.
Paganpatrick in reply to
Agreed. But as stated this is what I have heard ‘’some’ Doctors refer to it as.
in reply to Paganpatrick
I can"t disagree with you having heard some doctors use the word augmentation in the way you say.
I've never heard it used that way, so wouldn't know.
However, as you may realise, it's not what"s being dicscussed in this post.
At the end of the day augmentation simply means ‘adding to something’ the reasons behind it are multiple and secondary. As I’m sure your aware.
I want to thankyou (& everyone else) for taking your time to try to answer my question about Augmentation. If you go by the “Merriam-Webster” dictionary “Augmentation”: Enlarge;Increase. And, have/had been “warned” that I need to get off Ropinirole ASAP! That I probably will experience my RLS but there was other medication I could be taken without experiencing Augmentatiom! (Basically going back to the problems I had with my legs prior Ropinirole!) I took other medication when I had been hospitalized (Many times, in fact .) But, what people don’t seem to understand or grasp - I don’t care about Augmentation! I just want relief from RLS. Nor do I care if my medication is increased to make that hsppen! I mean what could happen? I die from it? Not today!!!!!
I understand your frustration and the distress/pain your in. Relief is what your looking for. At least now you can move forward and make a decision with more information than most doctors could/would tell you! See what medication is offered and make a choice which you can change later. I took very strong opiates with spinal pain which I was very glad of at time but also glad to be off of at later date. Know not exactly the same but you know what I mean! Best of luck, let us know how you get on.
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