Sent: Sunday, April 24, 2011 6:34 PM
Subject: Mirapex and Remeron
I am doing very well on Remeron for PTSD and depression except for RLS. Keeping me up every night. My doc recommended adding Zyprexa but I worry about huge weight gain possible if I take both, Remeron is bad enough. All my sibs have diabetes but I want to continue avoiding it . Would Mirapex stop the RLS without the risk of diabetes or is there an interaction there that would not be safe?
Mirapex does not worsen or interact with diabetes or any drugs used for diabetes. Remeron and Zyprexa can both worsen RLS symptoms.
Zyprexa does not cause or trigger diabetes. It may cause hyperglycemia (increases in blood sugar) which is a concern for patients with diabetes or elevated fasting blood sugars (borderline diabetes) as it may increase their blood sugars. There are also case reports of hyperglycemic comas induced in patients without diabetes taking Zyprexa, this is much more unusual and typically is mainly a concern amongst patients with an established diagnosis of diabetes or borderline diabetes.
A Reply from Judy
Sent: Sunday, April 24, 2011 8:09 PM
Subject: Re: RE: Mirapex and Remeron
I do not have diabetes. But I have read that Remeron causes weight gain and might trigger diabetes. Still, it has eased my depression so well that I am willing to continue it and FIGHT gaining the weight. However, when I was given a script for Zyprexa to help with the RLS the Remeron also causes, I found that Zyprexa is worse about causing weight gain and diabetes than Remeron.
Since I am at high risk to develop diabetes, taking the Zyprexa for RLS is just crazy. So, I'm asking, what about taking Mirapex with the Remeron instead? I have to be treated for PTSD and depression and the Remeron works, I just DO NOT want to develop diabetes if I can avoid it.
I am somewhat confused about you being prescribed Zyprexa for your RLS as this is not an RLS drug and typically makes RLS worse. Therefore, there would be absolutely no sense to do prescribe Zyprexa for RLS. Mirapex and Remeron would be a reasonable combination and should not result in any increase in problems.
Sent: Monday, April 25, 2011 1:23 PM
Subject: Treatment for RLS
I have had RLS for over 50 years. Until the last 10 years or so I didnít take any medication although at times I thought I was losing it because of the way my legs felt once in a while. But now, they bother me every day at any time of the day or night. I have been taking Mirapex (1.5 mg a day) and most of the time this does the trick but once in a while it get so bad that nothing helps unless I take 1/2 a Xanax tablet.
I have tried Requip but after a day or two of taking that My RLS symptoms get so bad I I feel like banging my head on the wall or something. Now my doctor says I have to stop taking Xanax although I only use it once or twice every two or three weeks.
There is little (if any) concern about taking Xanax (alprazolam) on an
intermittent such as you are doing. I am not sure why your doctor wants you off
this medication (there may be other issues than you and I are not aware of).
Xanax is not an RLS but does help RLS patients get to sleep (in which case,
Ambien or Lunesta will work as well).
The concern is that you may be having augmentation (worsening of RLS due to taking Mirapex) problems from your Mirapex. That is what may be worsening your RLS in which case you may need to change classes of RLS medication (that must be done very carefully as you can read in our many other letters).
Sent: Wednesday, April 27, 2011 7:18 PM
Subject: PLMD taking Requip with rebound.
I have had PLMD for 2 years. Took Ambien and Remeron for those 2 years. Both have worn off, so am taking Requip 0.25 mg. nightly with 10 mg. Ambien, and 45 mg. of Remeron. Sometimes take 3 mg. Lunesta to get away from the Ambien.
I've been taking the Requip for a month with good nightly results, but am getting really bothersome Restless Leg Symptoms in my left foot during the day. Tingling, numb, achy feelings in my left foot.
I have a history of Liver Disease from Hepatitis B, 35 years ago, so am usually ok as long as I stay away from Rx drugs that heavily process through the Liver. My Liver doesn't hurt yet, but feels tender. The Pharmacist said that Requip doesn't cause any Liver damage, but can raise Liver enzymes.
I'm concerned about long term use of Requip regarding my delicate Liver situation, and would like to find a "Liver Friendly" drug for my PLMD.
There are a few issues with your current treatment.
Remeron typically makes RLS worse so that might be part of your problem. Alternating Ambien and Lunesta adds no medical benefit as they act upon the same receptors. They do have different half-lives (Lunesta lasts much longer than Ambien but not Ambien CR) so that would be the only reason to take one over another.
Requip is metabolized by the liver so you may be experiencing higher levels of the drug in your body if you have significant liver problems. It does not in any way injure the liver or cause elevated liver enzymes otherwise. Mirapex is not metabolized in the liver (it is excreted through the urine) so is generally preferred in patients with liver dysfunction.
However, there is another issue to be concerned about. It sounds as if you are developing augmentation (worsening of RLS from taking a dopamine drug like Requip) in which case it may be better to get off Requip (and this would apply also to Mirapex) but stopping the drug must be done with caution.
A Reply from Brad
Sent: Thursday, April 28, 2011 8:24 AM
Subject: Re: PLMD taking Requip with rebound.
For now, do you know of any "liver friendly" sleeping pills, sedatives, benzodiazepines that are compatible with the Remeron, Requip?
My sleep medicine doctor prescribed temazepam 2 months ago, which made my liver hurt and expand, so I had to stop taking it, and go back to Ambien/Lunesta.
It is difficult to say why you experienced ďliver painĒ with temazepam as it
is not metabolized by the liver but rather excreted out through the urine.
Although I am not a liver specialist, I have prescribed temazepam and other
benzodiazepines to patients with liver insufficiency without any complaints or
side effects (or anything even close to what you are describing).
Therefore, you may be experiencing something that is unique to you and it is difficult to advise you on how you may respond to other benzodiazepines. However, Ambien and Lunesta are my two favorite sleeping pills so I would stick with them (unless you have reasons to change).
Sent: Friday, April 29, 2011 7:23 PM
Subject: Can Requip cause RLS ?
I was seeing a sleep specialist a few years back to try and help with the terrible insomnia I was experiencing. We tried a sleep study and sleep apnea wasnít the problem. We also tried every type of sleep medicine there is with very limited result. We tried relaxation techniques and nothing seemed to help. After all this and several visits to this physician, at one of my follow up visits with him, I made mention of an occasional hypnic jerk just as I was drifting off to sleep. It was a very infrequent occurrence.
I think he was at the point of grasping at straws so he prescribed a low dose of Requip just before bedtime. I think it was .5 mg once nightly. He did this thinking I might have mistaken hypnic jerk for RLS. But I never in my entire life had the symptoms of RLS until I took that first dose of Requip. I immediately began having that creepy sensation in my legs and violent jerking that would only be relieved by movement. It is most miserable because there is no way to relax and bedtime is now associated with a feeling of dread.
Anyway after some time passed my wife and I recognized symptoms I was having that lead us back to this doctor and I was referred to a Neurologist which ended in a diagnosis of Parkinson's Disease. I asked to be referred to a movement disorder specialist and eventually was titrated up to 8 mg of Requip a day. When the Extended release came out, I was changed to 6 mg daily of it. All the while I was continually having these RLS symptoms about 2 to 3 nights a week.
Recently I began having some uncontrollable compulsive problems and my wife and I discussed these with the Dr. Together we decided to wean me off the Requip and Introduce a low dose of Sinemet. She also prescribed a very low dose of Klonopin to help ease the RLS symptoms. Nothing works. I havenít slept over 2 hours total in a week. I am following the withdrawal titration schedule to the letter. But every night or anytime I am even sitting at rest, I have these awful RLS symptoms. I never ever experienced anything like this before taking Requip and I am completely convinced that Requip is the cause. What are your thoughts?
Your case is clearly somewhat unusual. We do know that RLS is more common in
patients with Parkinsonís disease (about twice as frequent) so there may be some
link there. It is possible that you had very mild RLS and by taking Requip, you
have developed augmentation (worsening of RLS from taking a dopamine agonist).
If that is the case, then Sinemet would continue to drive the augmentation
problem (this drug is actually worse for augmentation than Requip or Mirapex).
Klonopin is not an RLS and does not ease RLS symptoms. It is a potent benzodiazepine sedative drug that simply enable RLS patients to fall asleep despite being bothered by RLS symptoms. It is one of my least favorite drugs (please read the many responses about this drug for more information).
The treatment for augmentation is to get off the dopamine drugs (which may be a problem with your PD) and take opioids (methadone, oxycodone) for a few weeks due to the marked worsening of RLS that typically occurs when stopping a dopamine drug.
Sent: Friday, April 29, 2011 5:56 PM
Subject: Please help me
Hello! I have had RLS ever since I was a child, but no one ever knew what it was until I was about 23 years old. My family doctor that I had gone to since I was a teenager refused to treat me for it. So I started going to another doctor. He has tried me on a bunch of different medicines including Lyrica, iron supplements, temazepam, Requip, and most recently gabapentin. I feel like I am constantly battling RLS. I have always had to take a high doses of all the medicines above. A few weeks ago my RLS got considerably worse.
I told my doctor that to control it I had to take 600 mg of gabapentin during the day and 1200 at night. He increased my dosage to 600 mg every 9 hours. After a week or two of being on 600 mg during the day and 1200 mg at night, it no longer works. I have cut out caffeine, drastically reduced sweets and sugars, quit my anti-depressant and do yoga 1-2 times per day. I cannot take any over the counter pain medicine for my bad migraines or stomach medicine (like Pepto-Bismol) without it driving my RLS completely over the edge.
I feel like my doctor is getting aggravated with me. I have suggested, about halfway through my list of prescriptions, tramadol since I have been given some for back problems once and it worked fantastically. He flipped out at this request and suggested something else. I feel like he is not getting the seriousness of this condition. Sometimes he leaves me for days when a medicine stops working before prescribing me another.
I cannot take it. How can I stress the intensity of my RLS without overstepping my boundaries. Also, is there any medication you recommend that is not in the same families I have already listed? I have been thinking of finding a different doctor, but I have no insurance so it can get difficult. What do you suggest? Anything would be helpful. I have an appointment with him next week.
The problem that you are experiencing finding treatment for your severe RLS
is unfortunately very common. Most doctors (and even most of the doctors who are
considered RLS specialists like neurologists and sleep specialists) have very
little knowledge on how to treat RLS that does not respond to dopamine drugs
(Requip, Mirapex) and anticonvulsants (Lyrica, gabapentin).
Tramadol is actually a very good choice and if that is not potent enough, then opioids (given in low doses) are very effective and very safe (despite what your doctor will tell you) when monitored carefully.
Sent: Saturday, April 30, 2011 12:46 PM
Subject: Severe RLS
I live in Canada. I have had Restless Leg Syndrome for about 7 years. I have been treated by my Family Doctor, respirologist/Sleep disorders and now seeing a neurologist.
My RLS is severe and I am finding it hard to cope. My RLS covers all symptoms of the condition from tugging, itching, burning, creeping, hot legs, cold legs, pain all night. I move all night.
I have had all the testing done many times, iron levels are okay, no underlying conditions.
I have taken every medication there is to treat this condition the only one that did work was Mirapex which I have taken for a long period of time and took myself off of because of a terrible compulsive gambling addiction from it. The last Doctor I am seeing is the Neurologist who just did all the tests again and put me on Sinemet which I was on a year ago. I now have RLS all day (augmentation)?
Guelph, Ontario, Canada
Augmentation occurs extremely frequently from Sinemet, however once the
medication is stopped the RLS returns back to baseline (where you were before
you started the Sinemet) so it is unlikely that your former use of the drug (I
am assuming that you have been off it since last year) is responsible for your
increased RLS symptoms.
If you have already tried gabapentin and Lyrica, then the next drugs on the list to try are the opioids. For severe RLS, typically the more potent ones (methadone, oxycodone) are the ones that work best. Despite the fact that these drugs are both very effective and safe (when monitored closely), you will have trouble finding a doctor who will prescribe then to you (doctors donít understand the use of opioids for RLS and are generally reluctant to prescribe then anyway).
With proper treatment, you have an excellent chance of controlling your RLS symptoms so that they will not be an issue.
A Reply from Debra
Sent: Saturday, April 30, 2011 5:14 PM
Subject: RE: Severe RLS
Thank you four reply I was prescribed Sinemet again 3 days ago so I went off Mirapex and on Sinemet . Since starting it as I said my RLS has become even worse, I decided not take it. I have taken gabapentin and that didn't work either. Lyrica I have never used.
I know no doctor will prescribe any opioids here. I am running out of options. I even go to emergency crying and they won't do anything.
Guelph, Ontario, Canada
You may have to search harder to find a doctor who will prescribe opioids.
In order to help you, you may want to get a copy of my book for patients, RLS: Coping with your sleepless nights (profits from this book go to the RLS Foundation). You may also consider getting my book for doctors, Clinical Management of Restless Legs Syndrome to help guide your doctor on how to treat your RLS problems. It discusses the use of opioids at length.
A Reply from Debra
Sent: Friday, May 13, 2011 6:39 AM
Subject: RE: Severe RLS
I saw my family doctor who I started off with concerning RLS and explained everything to him. He listened. I told him about your advise etc. He said there are only a few doctors that are able to prescribe methadone here in Canada. They are at the drug treatment centers where addicted people go for methadone treatment. My doctor said we could try this on a trial basis.
My next step is I have to contact this center. They probably have never had a request like mine before. And they may not except me..
When I contact them what do I say? I would only need Methadone daily in the evening I think and what would the dosage be?
There is no standard does. We start with 5 mg and increase to 7.5 (1 Ĺ tablets) then to 10 if needed. Most donít need more than 10 mg per dose but a few may go as high as 15 mg.
Sent: Tuesday, May 03, 2011 12:53 PM
Subject: 9 year old with RLS?
My 9 year old had a sleep study and showed excessive limb movements are causing interrupted sleep. The doctor wants to try Requip. My concerns are:
1. I can't find anything on children taking Requip (pros/cons)
2. If his sleep is interrupted, this means his brain can not produce dopamine on its own. Why not treat the sleep disorder versus giving him synthetic dopamine? Won't the poor quality of sleep affect other things?
3. If the synthetic dopamine causes his leg movements to stop, thereby,
letting him rest with deep sleep - will his brain produce dopamine on its own,
thereby causing some sort of "overdose" situation? There is such a thing as too
much dopamine too, isn't there?
From what you have written so far, it is not clear that your son has RLS
(which are strange sensations in the legs which occur at rest and "force" the
patient to move or walk) as they are daytime symptoms which only occur while
What is clear is that your son has PLM (Periodic Limb Movements) which are very common in patients with RLS but actually many patients with PLM do not have RLS. There is great controversy about treating PLM when RLS is not present. Although these PLM may cause arousals (and I would have to know the PLM arousal index which is how many PLM arousals occur per hour to determine the severity) from sleep, it is not certain whether they result in "poor quality" sleep and need to be treated (even the most expert doctors are divided).
Although the PLM (and RLS) respond to dopamine drugs we have no idea if this is due to a dopamine deficiency (unlikely) or dopamine dysfunction or it may even have little to do with the body's own dopamine system. Therefore, there are no answers to your questions about dopamine.
Although I do treat some children with severe RLS with dopamine agonists like Requip, these drugs are not FDA approved for children and have not been well studied in this population. I would advise extreme caution when using these drug in children for PLM without the need to treat very bothersome/disruptive RLS symptoms.
A Reply from Gabrielle
Sent: Tuesday, May 03, 2011 7:05 PM
Subject: RE: 9 year old with RLS?
His limb movements were recorded as 15 per hour. He is also being labeled as having "ADHD." I use quotes because I feel this diagnosis is often wrong...that the kids just have symptoms due to something else but ADHD is the disorder "du jour." I appreciate you taking the time to reply...also, in case it matters, we did a daytime nap study. He only slept once (in 5 tries) and then only in the last 5 minutes before they woke him up.
I have idiopathic hypersomnia, & take Provigil (200mg once/day). He does complain of waking up a lot, is fidgety & high energy, but has not complained of crawling sensations in his legs, ever.
Although PLM are normal when under 5/hour, 15 per hour would be considered as mild. The old classification (this has been discarded due to the controversy over whether PLM are a real problem by themselves that need to be treated) rated 5-25 as mild, 25-50 as moderate and over 50/hour as severe. Furthermore, these should be PLM with arousals and it is quite likely that most of your sonís PLM where not even with arousals (you would need to look at the sleep study to ascertain this information).
Sent: Wednesday, May 04, 2011 1:34 AM
Subject: RE: Chemo
I have been burned very badly (large open wound) from the radiation therapy. It is so bad, they had to stop treatment. They prescribed Percocet for the pain. I noticed it helps with the RLS. Does it have the potential to have any negative affects on my RLS?
We often use oxycodone (Percocet is oxycodone and acetaminophen) for RLS which like any opioid helps RLS symptoms dramatically. You may notice an increase in RLS symptoms when stopping the Percocet only because you wonít be getting as potent RLS treatment when off the drug.
Sent: Monday, May 09, 2011 9:15 AM
Subject: Requip XL/Mirapex ER Questions
I'm currently on tramadol (75-100mg 3-4x/day) for all day RLS. I've been on Requip and Mirapex in the past, which worked at night, and at a reasonably low dose, but led to very bad rebound in the morning. My doctor at the time was very inexperienced with RLS and I don't remember really trying different doses of Mirapex or Requip in the morning to try and extend the efficacy of the dose and ward off the rebound. I did try a second dose a few times after the rebound had already appeared, which didn't help. After Mirapex I saw a new doctor and switched to Vicodin for a year, and then tramadol for the longer half-life and lower addictiveness, which I've been on for about 4 years successfully RLS-wise.
The problem with tramadol is that it has always caused very bad urinary issues (urinary hesitance, frequent nighttime urination) and the nighttime urination interferes a great deal with my sleep (get up 3-4 times per night in my mid 20's). I am fairly confident that tramadol is the problem as opiates often cause these problems and the problems began around the same time I started using Vicodin.
In order to get off the tramadol my doctors (new yet again) are slowly switching me over to Neurontin, but I've yet to really get off the tramadol so it's tough to evaluate how well it's working. We're hoping to wean me off tramadol and onto Neurontin over 4-6 weeks.
However, I've just become aware that both Requip and Mirapex now have extended release formulations, Requip XL and Mirapex ER, which may be able to help with my rebound/length of efficacy issues. How do these extended release formulations tend to handle rebound, and do they seem like they may be a good option to discuss with my doctors? Also, how does the somnolence/fatigue usually compare between Neurontin and the dopamine agonists, particularly during the daytime? One of my biggest fears with switching over to Neurontin is the sleepiness it might cause, when sleepiness caused by RLS and lack of sleep is exactly what I'm trying to cure! Thanks for your help in the past and once again!
It is not clear that your problem is rebound. Typically,
rebound does occur in the morning as the dose of the dopamine agonist wears off
but taking a higher dose at bedtime or an additional dose in the middle of the
night (when you get up to go the bathroom) would easily solve that problem.
If your RLS symptoms are occurring earlier in the day (morning and up to the afternoon if you never had symptoms at that time off Mirapex or Requip), then augmentation is more of a concern (and more likely). If augmentation is the issue then increasing the dose of short acting dopamine agonists may make it worse. The longer acting dopamine agonists may work better with less augmentation but we are still looking at that.
As such, using Requip XL or Mirapex ER may be helpful but it is important to figure out what was really going on. Neurontin is a very unpredictable drug (absorption problems and side effects do include a high frequency of sedation) so is typically not one of my favorite drugs. A new version of this drug (Horizant) has just been approved and will be available in July and should work much better. In the meantime, Lyrica may be a good alternative.
A Reply from Anon
Sent: Tuesday, May 10, 2011 7:52 PM
Subject: Re: Requip XL/Mirapex ER Questions
How do Neurontin/Lyrica compare to Mirapex ER/Requip XL in terms of daytime somnolence generally, particularly waking up in the morning and through the afternoon?
This can only be answered on a case by case trial of the drug. In general, the anticonvulsant drugs tend to cause sedation more frequently than the dopamine agonists but this varies widely from person to person.
Sent: Tuesday, May 10, 2011 2:36 PM
I have RLS and have been on Mirapex for about 7 years or so. I've had RLS symptoms for about 40 years. I'm 70 now the Mirapex controls my symptoms very well but periodically I have to increase dosage by .125 mg and that works for a year or more. my dosage now is 7 pills a day (.125 mg each) or .875 mg. I am starting to have signs that I need to increase my dosage again. my family doctor may be reluctant to prescribe an increase.
I have almost no side effects now and never have. do you think 1 mg is too much?
It is possible that you are developing augmentation which
is a worsening of RLS due to taking a dopamine agonist like Mirapex. If you are
developing symptoms in other body parts (other than your legs), finding that
symptoms are occurring earlier in the day or the symptoms are becoming more
intense and you canít sit as long (except for a short while after you increase
your Mirapex dose), then augmentation is extremely likely.
If that is the case, you will likely to continue needing increases in your Mirapex dose. It may then be necessary to change to another class of RLS medication.
Sent: Tuesday, May 10, 2011 11:49 PM
Subject: Need Help Switching from Methadone to Tramadol
In 1998 I began taking Permax for severe RLS and over the next 5 Ĺ years worked my way up to 3 mg. daily. Because of augmentation my doctor then switched me to Mirapex which I took for the next 5 1/2 years and, again, worked my way up to 3 mg. daily. After the first 3 years or so, I began having augmentation of RLS symptoms again so my doctor recommended a low dosage of methadone daily (7 Ĺ mg. twice daily).
I have been taking the methadone for 1 Ĺ years now and it works very well for the RLS in helping me sleep all night; but I am extremely sleepy during the day and I have the most horrid ďhot flashesĒ several times every day to the point of dripping with sweat and being red-faced most of the time. Recently I went on a 3-day trip out of town with my daughter (who also has severe RLS) and was mortified to discover I had forgotten to bring my methadone with me.
Of course I cannot obtain methadone without a written prescription from my doctor, so, luckily, I was able to take my daughterís tramadol. I took two 50 mg. tramadol tablets twice daily during the next 3 days and it worked great. I was not sleepy in the least during the day. When I got home, however, I reverted back to the same dosage of methadone I had been taking before and was not able to sleep for the next 3 days.
After much research on the web about methadone, I realized that it takes a while to build up in your body and around the 4th day, my RLS was finally put to rest again. I went to my RLS doctor (a neurologist) shortly after that incident and told him I would like to take tramadol instead of methadone because of the extreme sleepiness and sweating caused by the methadone. He was okay with that so I quit the methadone cold turkey (total of 15 mg. per day) and began taking one 50 mg. tramadol tablet at noon and two 50 mg tablets at bedtime.
By the 3rd day of this regimen I was feeling horrible and
was hardly sleeping. My face was red all the time and I was sweating non-stop.
In general I felt like I was coming down with something like the flu. I was
miserable! So, I started back on the methadone and, again, it kicked in around
the 3rd or 4th day. I absolutely hate how the methadone makes me feel and would
still like to switch to the tramadol but obviously need to wean myself off the
Can you please advise me how to wean myself off the methadone and how much of the tramadol to take while doing so?
It is actually unusual for methadone to take a few days to
ďkick inĒ when treating RLS symptoms. Typically, most RLS patients get relief
with their first dose even after being off the drug for an extended period
(weeks or longer). This may work differently for treating pain.
Sleepiness is one side effect that often limits the use of methadone. Otherwise, it tends to be one of the best opioids for treating RLS. You may want to try other opioids (like oxycodone) to see if they help your RLS without sedative side effects. It may take a trial of several opioids before finding the right one for you.
An additional choice is the anticonvulsant drugs which include Lyrica, gabapentin and the soon to be released Horizant. These drugs also may cause sedation but that is a separate issue from the sedation you have experienced from methadone.
A Reply from Phyllis
Sent: Tuesday, May 24, 2011 12:59 AM
Subject: Need Advice About Methadone Dosage
I am a 62 year old female with severe RLS. I took Permax and Mirapex over the last 11 years but, because of augmentation while taking those drugs, I am now taking methadone twice per day (7 1/2 mg each time). The methadone works great for the RLS but makes me unbelievably sleepy all day. This extreme grogginess has completely changed my life in that I no longer have the energy to do anything I used to do and have become something of a recluse.
I absolutely hate living this way and was wondering if it
is possible to delete my afternoon dose of 7 1/2 mg of methadone and take only
the nighttime dose. If not, what other options do I have? I am very sincere
about the extreme degree of sleepiness I am experiencing.
You do have lots of other options.
You may try other opioids (such as oxycodone) or even tramadol (a non-opioid that works like the opioids but less potent). These may have less sedation (or more) depending upon you react to the drug (no way to predict until you try them).
You might want to change to Lyrica (may cause sedation also but you have to try it first to see), gabapentin (not that good but cheap) or the new drug Horizant (a better type of gabapentin which will be available in July).
A Reply from Phyllis
Sent: Tuesday, May 24, 2011 8:30 PM
Subject: Re: Need Advice About Methadone Dosage
But how do I transition from methadone to tramadol and how much tramadol do I need?
That is a more difficult question to answer as it varies
from person to person.
The first and easiest way to try this is to take tramadol, 1-2 tablets in place of your morning dose of methadone and see how it works. If it does help (typically for 4-6 hours), you may need additional doses at 4-6 hours intervals. If that works well, then you can stop the methadone immediately and continue on the tramadol.
A Reply from Phyllis
Sent: Wednesday, June 08, 2011 9:13 PM
Subject: RLS , Surgery & Pain Medicine
I am a 62 year old female and for 1 Ĺ years have been taking two 7.5 mg. doses of methadone daily for my RLS. I had foot surgery a little over a week ago and my doctor discontinued the methadone and prescribed one 10 mg. tablet of Norco every 4 hours until the foot pain subsides which I am taking day and night. Although the Norco pretty much takes care of the RLS, I am having RLS symptoms during the day and wake up at night sometimes before my next dose is due.
I have some leftover Mirapex which I had previously taken for 5 years before the methadone (3 mg per day) so I started taking .25 mg an hour before bedtime in addition to the Norco during the day and night. I believe I am having withdrawal from the methadone because of the breakthrough RLS during the day and night and I am alternating from being extremely hot to extremely cold constantly. Also, I have absolutely no energy and feel quite miserable.
My questions are:
1) do you think I am having withdrawal from the methadone and, if so, how long will it last?
2) When I discontinue the Norco, will I again go through withdrawal and is there any way to minimize the suffering?
3) Do I need to take more Mirapex before I go to bed to keep the RLS completely at bay?
Also, I will say with the utmost of certainty that I will
never, ever go back to methadone (too many issues with it).
You are coming to an incorrect conclusion about methadone
withdrawal based upon the experiences you have just related. Most people do not
get withdrawal from methadone at the doses that you were taking. What you are
experiencing is lack of adequate coverage for your RLS due to stopping
methadone. Norco would adequately cover any withdrawal problem if that was
really occurring (but that is clearly not the problem) but it only lasts about
4-6 hours at best while methadone lasts 6-10 hours.
What you are experiencing from taking a shorter acting drug is lack of coverage of your RLS symptoms when the Norco wears off (whereas the methadone would have covered it very well). The surgeon could have left you on methadone for your post-operative pain as it would have taken care of that and your RLS quite well but most doctors are uncomfortable with methadone. If you still feel uncomfortable with methadone for other reasons then certainly stay away from it but your concerns about withdrawal are unfounded.
Be careful with Mirapex as since you have trouble with augmentation in the past, it may occur very quickly with the re-introduction of that drug. You should probably consider looking for other non-dopamine drugs to treat your RLS.
Sent: Wednesday, May 11, 2011 12:37 AM
Subject: RLS, peripheral neuropathy and varicose veins
I have been diagnosed as suffering from Restless leg syndrome and peripheral neuropathy. I would like to know if the peripheral neuropathy commonly associated with restless leg syndrome is similar to the neuropathy associated with diabetes. and can this neuropathy affect the heart and cause heart problems?
I have got varicose veins in my legs and my doctor has said
that this is due to blood pooling in the legs. I am not able to sleep at night
unless I elevate my legs. I also have low blood pressure. In this situation
which medication do you think would be good for me. I believe dopamine agonists
can reduce blood pressure.
Peripheral neuropathy tends to be similar no matter what
the cause. It is also fairly common with RLS but peripheral neuropathy does not
affect the heart in any way. For patients who have both RLS and peripheral
neuropathy, drugs like Lyrica or gabapentin are usually considered as the first
Dopamine drugs can cause low blood pressure issues but this occurs with standing up and may cause fainting rather than being considered a benefit for treating high blood pressure.
Sent: Wednesday, May 11, 2011 5:17 PM
Subject: Moderate to Severe RLS
I have been diagnosed with moderate to severe RLS that started about 6 or 7 years ago; I am now 57. I am currently taking 5 mg of Requip (Ropinirole) on a nightly basis an hour or so before I want to go to sleep, followed by 125 mg (2.5 tabs) of Tramadol about a half hour later, which generally puts me to sleep. However, having to go to bed ranges from Iím starting to get tired, to an intense feeling that I need to go to bed right now, with a very uncomfortable feeling that is really hard to describe; itís like I need to lay down NOW.
Also, there are times when the legs just wonít quite relax and it feels like I need to increase the Requip dosage so Iíll add another 1 mg and I can also go up another 25 mg with the Tramadol without feeling like Iím coming unglued. However, there are nights that I just seem to blow through these meds, about every two-three weeks or so, for up to 3-4 nights, when I need a half or a whole of a 325 mg Percocet (Oxycodone) to relax me enough to sleep (obtained from my wifeís migraine problems, as Iím in recovery for alcohol abuseÖwhich I figure was part of self-medication for the onset of RLS..could be circular).
At any rate, my Neurologist has said that he is going ďby
the bookĒ and started adding carbidopa/Levodopa to the Requip in the summer of
2010, then tried clonazepam but I did not like how it made me feel and it didnít
seem to help very much. Thatís when we tried tramadol in November 2010 and
thatís what Iíve been doing since then, but the relief has been sporadic.
One of the main reasons Iím writing though is that the RLS symptoms are now starting up in the afternoons, between 3-4 and 5-6, but if I can tough them out they generally subside until 9:30 or so at night, so I suppose Iím starting to experience augmentation, maybe? The neurologist Iím seeing has been hesitant to prescribe Percocet, although that seems to work best, for obvious reasons, but his next option was going to be methadone, which my wife is aggressively against, as a combination drug with Requip, but it sounds like that may have run itís course as well.
Perhaps Horizant will be a logical alternative? Also, there
have been several RLS doctors recommended on the national RLS site in the
greater Seattle/Bellevue, Washington area, some of which work in the Parkinson
Clinic/Section at Evergreen Hospital. I was wondering if it would be better to
try to switch doctors or try to pull the current doctor along with the search
for relief of my RLS symptoms?
You are quite correct in that it sounds as if you are
experiencing augmentation from Requip. If you increase your Requip dose, you
will get temporary relief but ultimately you will need more and more Requip as
your augmentation gets driven by the increased doses of this drug. At this point
I usually recommend getting off the Requip and changing to other drugs.
Oxycodone (not Percocet which also contains Tylenol which does not help RLS) is a reasonable choice as is methadone (these drugs are not all that different as far as addiction risk but methadone typically treats RLS much better). The only concern is your previous drug abuse issues. However, if your opioid use is monitored carefully, this problem can usually be circumvented.
Horizant (it will be available in July) will be a reasonable alternative as is Lyrica. These drugs may have to be used in combination with opioids but they will then allow a lower dose of opioids to be effective.
Your neurologist may have been going by the book when prescribing clonazepam and Sinemet (carbidopa/levodopa) but it is a very old book as these drugs have not been used by RLS specialists for over 15-20 years.
The list of RLS doctors on the RLS Foundationís website (www.rls.org) is merely a list of doctors who say that they treat RLS and does not imply any significant expertise for this disease. These doctors may be better or worse than your current neurologist.
Sent: Wednesday, May 18, 2011 12:53 PM
Subject: PLMD and Restless Leg - Medication Relationship
I had cancer in 1996 and after the chemo stopped I developed what Mayo later said was an unknown autoimmune disease causing small fiber neuropathy full body pain much worse with movement. During the two years it took me to get to Mayo Clinicís diagnosis I saw many baffled doctors in the Washington DC area. I didnít want to mask the symptoms so I sat still all day and used a wheelchair. It was during this time that I was given clonazepam to help me sleep through the pain at night. The illness ramped up in magnitude and spread through my body when I was diagnosed with this illness, related to the chemo I had received, Mayo said that I need to come off of the 3mg of clonazepam I was taken.
Mayo suggested Neurontin and MS Contin which I took for years. I developed PLMD at night after coming off the clonazepam. I was put on clonazepam 1mg for the shocks that my body felt when I tried to sleep and Xanax. I became tolerant of the Xanax after 5 years and was switched to Mirapex with the goal of coming off clonazepam in the future. I am blessed to say that my autoimmune disorder has disappeared within the last year and I am no longer on MS Contin. It has been about 6 weeks and of course I had severe symptoms of RLS for 8 days after gradually coming off of it over 8 months.
I was given Lortab as one of the medications to assist me with this symptomatic withdrawal. I didnít need them after 10 days and found that without the MS Contin I had very bad RLS not just the night time PLMD anymore. I assume the medication was masking the true RLS symptoms which are relentless. I have gone from my previous dose of 3 mg of Mirapex and .75 mg of clonazepam (I had reduced from 1 mg 6 months earlier) to 5mg of Mirapex at night and 1mg at 10AM. The aching that is new and a creepy feeling during the day gets so bad that one Lortab 25/500 seems to do it about 11 AM. I use to sleep fine at night but I was on the MS Contin too.
I now have problems that seem worse since increasing my Mirapex dose. I wake up at about 4AM and canít get back to sleep my legs donít feel bad just enough to wake me. I have tried Requip prior to ever taking Mirapex it didnít help the PLMD. I really donít want to take any narcotic if I can avoid it. It is so wonderful not to need that type of medication. Is there any substance to the claims stuff like ALL CALM work to help RLS? I want to feel good again and would like to try and come off of Neurontin although I know it can help RLS. Is this an augmentation problem with increase in Mirapex? I have been on it about 7 years. I know my case is complex but I could use your input.
You do have a complex case and it is hard to advise you on
what you have and what you should do. It is quite possible that you do have
augmentation from Mirapex which can occur even several years after starting
All Calm has only anecdotal evidence that it helps RLS (which is likely as good as any placebo for treating RLS) so I would not recommend wasting your money on this product.
Sent: Wednesday, May 18, 2011 2:03 PM
Subject: Need Daytime Relief
I was diagnosed with RLS about 15 years ago and eventually tried several of the traditional medications for relief. I currently take 8mg of the generic of Requip each night as well as 1 mg of Clonazepam and most nights get a good 7 to 8 hours with little interruption. If I wake up I usually go right back to sleep. Lately sometimes I wake up with foot or calf cramps about half the time, stand up for a minute and am able to get right back to sleep.
However, lately the daytime symptoms are getting intolerable. Usually about 2:00 in the afternoon they start and can last anywhere from 1 hour to the rest of the day. I also take .5mg of the Clonazepam about 10:00 AM to try and get me through the day without the symptoms. I also have recently experienced worsening symptoms during the evening. In fact, I had to travel by plane last week and had to stand most of the two 2 1/2 hour segments due to the maddening symptoms. Iím not able to make any plans for the evening time as my only relief is standing (usually watching TV or fiddling in the garage) until dinner (9:00) and I take the medication.
I may be having augmentation symptoms but the medication is
still working throughout the night for the most part. Due to the side effects of
the Requip Iím not comfortable taking it during the day. Itís to the point now
that almost have my day becomes unproductive as Iím not able to concentrate on
my desk job work. Forget any evening social life. Finally, I no longer eat lunch
as I noticed that about an hour after eating I would get drowsy and would almost
always experience my RLS symptoms.
Unfortunately, my most recent primary care physician (PPO) isnít very knowledgeable about RLS and I have pretty much told him how much Requip and Clonazepam to prescribe. Looking for some suggestions on how to deal with the worsening symptoms, specifically do I need to switch medications? Iím not into experimenting with any holistic trial and error methods as I never want to go back to those nights of 10 to 15 minutes of sleep at a time throughout the night.
Clonazepam is not an RLS drug. It is simply a
benzodiazepine (Valium like drug) that was found many years ago to help RLS
patients get to sleep. There are much better sleeping pills to take for treating
nighttime RLS symptoms that prevent sleep. Clonazepam is one of my least
favorite drugs to treat even bedtime RLS sleep related problems (please read the
many posts on our site about this issue) and it should not be used for daytime
RLS as it will just increase your chances of falling asleep during the daytime
while needing to be alert (such as when driving).
It does sound like you have augmentation and it is quite likely that it will continue to get worse. You could treat your daytime RLS with additional doses of Requip during the daytime which would probably help you for several weeks to months. As you are already on a very high dose of Requip (typically twice the recommended dose and much higher than I would use), I would not suggest that you further increase the Requip but rather follow your initial idea of getting off the drug. This is a difficult process that usually requires the use of a strong opioid (for at least a few weeks). Getting off the clonazepam should be done either well before this process or well after as you donít want to increase your stress unduly all at once.
A Reply from John
Sent: Thursday, May 19, 2011 10:20 AM
Subject: RE: Need Daytime Relief
The clonazepam really doesnít make me tried at all; Iíve probably developed some resistance to it. My major concern is the daytime symptoms but really donít know if the nausea etc. side effects of the Requip might not be worse than the RLS symptoms. I called your office yesterday afternoon before posting to make an appointment. I am concerned that my current primary care physician is not educated in RLS and having me trying to educate him on going forward would be a long term challenge.
The route Iíd like to take is as you suggested in
your email below, get off the Requip with the help of a strong opiate, restart
the Requip and wean myself off the clonazepam. However, will restarting the
Requip with a sleeping aid relieve my daytime symptoms?
Iím looking at a change in jobs that will require that I travel by plane more often so would like to begin the process ASAP.
The side effect of nausea can often be helped (usually
quite significantly) by taking the Requip with food (this does delay the onset
of action by about 1 hour). However, restarting the Requip after being off it
most likely will just recreate the augmentation problem (and typically that
occurs fairly quickly) so that might not be a good option.
Your daytime symptoms may disappear when you are off Requip for a few weeks.
It actually very common for patients not to perceive the daytime sedation from clonazepam (especially when they are getting somewhat tolerant) but when tested, they do show significant deficits of function (like on driving simulation studies).
Sent: Tuesday, May 24, 2011 3:06 PM
Subject: herbal Lumiday with RLS medicine?
I have just received a product that I ordered in the mail, and am wondering if it is compatible with Mirapex (1.5 mg) and hydrocodone (5 mg) which I take for RLS. The product called Lumiday, is for emotional well-being, easing stress and anxiety, etc. In it are:
Vitamin D3, B1, B3, B6, Folate B9,B12,B5, L-Theanine 99% (200 mg), 5- HTP,100 mg, Saint Johns Wort 300 mg, Rhodola Rosea extract 100 mg, Ashwagandha root 50 mg.
Is this something I can take and not compromise the RLS medications?
GP in Taos, New Mexico
Like all OTC products that contain a variety of active
ingredients, it is impossible to say how it will react with your RLS. These
drugs have very little control on them and are not studied well (if at all) for
interactions with other medications.
There is nothing in that preparation that strikes me as RLS unfriendly but I really can't be confident in assuring you that it is safe for your RLS.
Sent: Thursday, May 26, 2011 11:41 AM
Subject: Tramadol for RLS?
I am taking Requip xl 4 mg for RLS as prescribed by my neurologist. Recently, I was diagnosed with fibromyalgia by my primary care PA and have been given tramadol 50 mg for the random and, at times, debilitating pain. My neurologist is not "sold" on either fibromyalgia or tramadol. The discussion felt like a "turf war" and my question is: Can I safely take tramadol as needed?
We use tramadol very often for RLS. It works about as well as hydrocodone 5 mg (one of the ingredients in Vicodin) for most RLS sufferers. Although a minority of patient experience side effects (usually mild), it most often well tolerated and quite effective for RLS or pain (any type of pain including that of fibromyalgia). I am not sure why your neurologist is not that keen on this drug but in general, it is a reasonable choice for RLS and pain problems.
Sent: Monday, May 30, 2011 3:05 AM
Subject: Treatment for severe RLS?
I'm 22 years old and I've been suffering from RLS for over 2 years and I'm going insane. My symptoms have been getting increasingly worse over the past 6 months. My doctor started me on 300 mg of Neurontin and currently I'm taking 2400mg a day and 100 mg of tramadol. I find the Neurontin makes me feel...well dumb and forgetful at times and is no longer effective in treating my RLS.
I hurt my back a few months ago and was prescribed Percocet, when I took it I felt instant RLS relief. I mean the birds sang, flowers grew, I felt like a human being again. This coming from the girl who fractured her knuckle from punching a walk because wanted to stop her hand from moving. I'm not sure how to approach my doctor about this. He is a family friend but I don't want him to think I'm a junkie because I am so young. I'm just not sure what else to do because NOTHING has ever taken away the symptoms like that EVER.
I'm also wondering if it's a lasting treatment, as in should I do it my whole life? I'm sure you get tons of emails but I'm so desperate and you seem like the only doctor who knows what he is talking about. Please help me, I really don't know what to do.
Neurontin (generic is gabapentin) is well known for causing
sedative effects especially at the doses that you are currently taking (most
patients can't get even close to that dose without feeling like a zombie).
Tramadol is a reasonable RLS drug and often works as well as the moderately
potent opioids (like the hydrocodone in Vicodin).
Potent opioids like oxycodone (which is the opioid in Percocet) typically work incredibly well for RLS symptoms. We do actually use them a lot but only after other non-controlled drugs have proven unsuccessful. You should first have a trial of a dopamine agonist such as Mirapex or Requip as they may work very well for you. If these do not work for you then Lyrica (somewhat similar to Neurontin but typically fewer side effects) may be a good alternative.
If all the above does not help then oxycodone (not Percocet as the Tylenol in Percocet does not help RLS) is a reasonable choice. Methadone often works even better but you may have difficulties getting your doctor (or any other doctor) to prescribe either of those drugs.
A Reply reply from Jenna
Sent: Monday, May 30, 2011 6:31 PM
Subject: Treatment for severe RLS?
Thank you so much for getting back to me so quickly! I tried to buy your book today but they didn't carry it at the book store so I'm going to order it online. I was first prescribed Requip by my doctor and it did nothing. I then tried Mirapex and it did nothing but make the pain worse, it also gave me hot flashes, I found myself randomly falling asleep, once while driving. Needless to say I never took it again. I'm also trying to convince my family that pain meds are a reasonable method of treatment, but with such a stigma it's a hard sell.
I enrolled in a methadone clinic and it did wonders, the only problem was it was $14 a day so cost wise it's not ideal. I was also reading online that pregnancy increases RLS symptoms, will I be able to continue the pain medication treatment when I decide to have kids? And also I was wondering if RLS decreases with age? I have tried: Requip, Mirapex, Neurontin, Xanax, Tramadol, Restoril, Ativan, Ambien, Lunesta, Topamax, Lyrica, and even marijuana at desperate times.
Most if not all of the above medications have had little to no effect, or will sometimes work for awhile and then stop. Mind you all of these meds have been prescribed in a 2-3 year span, so I've given up hope. Is there a reason why pain medication works so well? Maybe a certain chemical in it? I've just never had relief like this before, but I don't want my family and friends to treat me like a drug addict because I take them.
RLS does increase with age but very slowly. This may take
many decades or it may not increase at all (but most do get worse with time).
RLS does get worse (unfortunately, often very much worse) with pregnancy,
especially during the late stages. However, it typically returns back to
baseline shortly after delivery. The drug of choice for pregnant RLS patients is
We do not know why opioids work so well for RLS but then we don't know why any of the RLS drugs help the RLS symptoms.
As you have tried most of the available RLS drugs (Xanax, Ativan, Ambien and Lunesta are not RLS drugs but rather benzodiazepine sleeping/sedative pills that help RLS patients get to sleep), it would be very reasonable to go on oxycodone or methadone. You should not have to go and pay for a methadone clinic to do so. However, it will be hard to find a doctor to prescribe these schedule II opioids due to their controlled nature.
Sent: Monday, May 30, 2011 1:18 PM
I am wondering if you have any knowledge of the Flowtron Compression Pump, relating to possibly helping to relieve RLS.
Sue in the UK
The evidence for leg compression devices helping RLS is still sketchy so it would be very difficult to evaluate a product that has not even been tested for treating RLS.
Sent: Tuesday, May 31, 2011 1:20 AM
Subject: Delayed sleep phase syndrome
I'm 46 and have had RLS since I was a child. I have RLS anytime of the day if I rest. I have been on Requip and Tramadol for about 10 years now 3x a day. My life is tolerable but sleep has always been an issue. I have tried small doses of Ambien but had quite a hang over the next day. I usually get between 2-4 hours of sleep per night. Seven weeks ago I had to go on an emergency road trip that consisted of driving 20 hours straight there resting two days and 20 hours straight back home.
I was very careful taking my RLS meds on time and did rather well with my RLS. However, I was deficient two nights of sleep and haven't seemed to regulate back to my regular ( crummy) schedule. I cannot sleep until about 4 am and wake about 3 1/2 hours later. I eat something and try to sleep some more but my RLS kicks in. I then take a dose of meds and try again a couple hours later and cannot sleep. This has been going on ever since the road trip.
I was searching on the web and read about Delayed Sleep Phase Disorder. The description seems to fit me to a tee. I have never been able to sleep before midnight as long as I can remember. I have tried at the obvious, sleep meds and changing sleep times, patterns, even sleep deprivation to adjust my clock but nothing works. Is DSPD a real syndrome and do some people with RLS have this other sleep disorder as well?
We all tend to have a little bit of DSPD which becomes
evident when most people find it so much easier to adapt to flying west compared
to flying to the east coast. However, most of us can reset our clocks eventually
(some sooner than others). Patients with DSPD have extreme difficulty making
this change (which may occur after travel or a change in schedule). This is a
very real disorder but can be treated.
Melatonin (or even better, the prescription melatonin receptor drug, Rozerem) often helps reset the body's clock and get people synchronized back to the correct time zone. It should be taken a few hours before bedtime.
Perhaps a shorter acting sleeping pill like Sonata (generic is zaleplon) may help get you to sleep but not hangover the next day. There are other techniques but the above 2 are amongst the quickest and easiest.
Sent: Friday, June 03, 2011 10:34 AM
Subject: RLS and fabrics?
My mom suffered for years undiagnosed, walking the floor night after night with "leg cramps that weren't really cramps"... She died in 1987 at 67. In her 50s, she realized if she avoided any contact with polyester or nylon (or PVC plastic) (really any fibers that are man-made) in her clothes, sitting on, holding near her body for any length of time, bare feet on carpet...she would sleep through the night and not suffer the "leg cramps" which was actually RLS symptoms. It was difficult to do, but she carried a sheep skin to sit on, or a piece of vinyl or used a hard chair. She used moccasins for slippers on carpeted floors. All her clothes were natural fibers and she could tolerate Lycra so found some "nylons" she could use. I was young and she never really explained it to me so I wish she was around now. I do know that she was almost symptom free for the last 8 - 10 years of her life. And I do know her doctors though it was "all in her head" and unreasonable. What I mainly remember her saying to me once was "if I hold my grandbabies in their little fuzzy sleepers I will be up walking the floor in the night".
My major symptom from my early 40s (after my mom died) was a 'hot' sensation in my feet, legs up to my hips which doctors always dismissed as "hot feet" and didn't ever offer an idea until last year my doctor suggested it was a nerve symptom and part of RLS. Of course I knew I had RLS, but that was nothing compared to the burning feeling (as I now realize I should have described it). Temazepam stopped the 'burning', but not all the RLS and I still seldom slept through the night, but at least it was 100% better. A couple of months ago the Temazepam was not working as well and all the symptoms began again. After a long weepy conversation with my sister about our mom I decided to try what my mom did. Within 4 days i noticed the Temazepam was effective again. After about a week I was sleeping through the night, but then I spent a day sitting on nylon padded seats and that night my RLS was worse than it had been for a very long time... it took a week of being careful again about my contact with certain fabrics and again I slept through the night and had no RLS when I did wake in the night.
I have changed my mattress pad, sheets, quilt, clothes
(thankfully there is a lot of cotton, wool and natural fiber clothes now
available, and 2nd hand stores to make it affordable.), I wear flip-flops on the
carpet and luckily we have a leather couch to sit on. I carry a leather, backed
with cotton, pad I made, to sit on padded seats, or I sit on my leather coat
(the lining is a sateen cotton). On a couple of occasions I have had extra
fabric contact - shopping in Winners - touching lots of clothes, sleeping
elsewhere with polyester bedding etc. Each time I have had a terrible night with
RLS and it has taken up to a week after to sleep through the night again, each
night being progressively better.
The more I talk to people and salesclerks (but not doctors), the more I hear comments about how many people they see daily who are staying away from manmade fibers. My local leather repair shop said she regularly puts new sock liners made of leather in shoes because it stops the "burning feet" some clients experience. Another acquaintance admitted she only wears cotton because it makes her feel "a creepy sensation" although she didn't speak of night time RLS.
I have searched the Internet about a connection between contact with fibers and RLS and found nothing. I am finally going to be seeing a sleep specialist again the end of the month because they are so busy in our area it's been a year wait. Everything my doctor tried (except the Temazepam) made the RLS worse. I expect him to prescribe one of the Parkinson's type medications.
Has anyone else ever looked into the polyester/nylon fabric connection? Several people (including medical) after hearing my mother's story said "could it be a connection to static electricity?" It certainly feels like electrical currents in my legs and lower back (plug in my spine and light up a small city I always said). My mother cannot be the only one who found relief this way. Of course, it requires a lot of effort (and money) to change a person's environment, so I realize it wouldn't be a treatment of choice for most people - drugs are quicker! But, it might explain why some days, months, are worse than others.
This might just be placebo effect (although why a placebo
effect takes a week to work..) and I might not get 10 years of relief like my
mother did...and yes I am still taking Temazepam - but at least I now sleep like
a normal person.
Is there anyone else out there who has made a connection between RLS and fabrics?
I have had extensive exposure to RLS patients both in my
personal practice (which is one of the largest RLS practices) and on this
website. However, I have never before heard of a connection between any type of
fabric (natural or man-made) and RLS. That of course does not mean that this
connection does not exist (especially in your case) but rather that it is
extremely unusual. Although the ďstatic electricityĒ connection is an
interesting idea, RLS is more complex than that. For example, patients with an
amputated limb can feel RLS in that limb (the so called phantom limb) indicating
that the RLS sensations are generated in the brain.
Temazepam is not really an RLS drug but rather a sleeping pill and sedative closely related to Valium. It does help RLS patients fall asleep and may calm some of the symptoms by causing sedation (which may decrease oneís perception of discomfort in general). However, if it is working for you then it is a reasonable choice but you must be careful as tolerance/dependence may occur with this class of drug (but could take many years to occur).
Sent: Friday, June 03, 2011 10:18 PM
Subject: Ambien & RLS
There are 3 main receptors in the GABA complex that are responsible for sleep:
Omega 1 - Sedation
Omega 2 - Anxiolytic (Anxiety or lack of inhibition)
Omega 3 - Myo-relaxant (muscle relaxant)
The reason Ambien does not help with RLS is that it has an affinity to bind ONLY to Omega 1 receptor. This is great for those who just need help sleeping. Benzodiazepines (Xanax, Valium, etc) bind to all 3 Omega receptors and assist in sleep, muscle relaxation and lowering anxiety. In my experience, benzodiazepines are the better way to go for RLS and leg relaxation.
You are quite correct about the three GABA/benzodiazepine
receptors. However, the action of drugs like Xanax that act on all 3 receptors
does not translate into any real direct benefits for RLS. The symptoms of
RLS originate in the brain (patients with an amputated limb can ďfeelĒ RLS
symptoms in that phantom limb) so having a drug that relaxes muscles does not
really help RLS. There may be some indirect benefits with respect to decreasing
anxiety levels which may then decrease the perception of discomfort but that may
not help every patient.
In fact, there is one article (an abstract that never got fully published) by Dr. Richard Allen that showed an increase in RLS symptoms with Xanax due to sedation and of course, RLS occurs more readily at rest when patients are relaxed. Typically, we only suggest sleeping pills or sedatives to help RLS patients fall asleep at bedtime.
Sent: Monday, June 06, 2011 9:12 AM
Subject: RLS Symptoms = Torture
I have had restless leg syndrome since as long as I can remember. As I have gotten older (about to turn 36 in a month), the symptoms have gotten much worse. When I move at night, I get instant relief, but the relief only lasts about 2 seconds. Whatís worse is that more and more parts of my body are experiencing the restless leg effect. About 7 years ago, my back and shoulders started to feel it.
About 3 weeks ago, however, my stomach started to feel it! I imagine the feeling is creeping into my abdominal muscles, but it feels as if the feeling is in my stomach and/or intestines. 4 years ago, my neurologist started me on .25 mg of ropinirole, but now I am at .50 and I only get about 4 or 5 hours of relief. In other words, the dose does not last through the night. I am usually up at about 5:00 AM tossing and turning.
The truth is that for the first time in my life, I am
seriously concerned with the quality of life I can look forward too. From what I
have read, this thing gets worse with age. If that is the case, then my future
is extremely bleak as my symptoms are already bad. I feel like I am being
tortured at night Ė and an increasing amount of day light hours as well. As I
write this, I am feeling that all too familiar sensation in my stomach. If this
is what I have to look forward to in life, I am surely going to be miserable.
RLS does get worse with time but this tends to happen for
most over decades. I suspect that the worsening of your RLS has less to do with
getting older but rather more to do with taking Requip (ropinirole). This drug
(like all the dopamine agonists) is well known to cause augmentation of RLS
symptoms (a worsening of the symptoms due to taking a dopamine medication).
Typically, an increase in dose helps for a while then symptoms get worse again.
If your RLS is also occurring earlier in the day (at least 2 hours earlier than
when you began the ropinirole 4 years ago), then it is very likely that you are
The good news is that this problem can be taken care of fairly easily by a doctor who understands augmentation and has experience treating it. Unfortunately, most doctors (including most neurologists and sleep specialists who are the local RLS specialists) know very little about augmentation and how to treat it. You can search our website which contains lots of information on treating this problem and share it with your doctor.
Sent: Monday, June 06, 2011 11:39 AM
Subject: Maxalt helps RLS?
I have pain issues, RLS and migraines. I stumbled o to the fact that Maxalt works really well on RLS attacks, but obviously it cannot be a daily rescue. Please, do you have any insight into this? Nothing else so far even touches the bad attacks and I feel like I'm losing my mind.
I have never heard of Maxalt or any of the other similar
triptan type migraine medications. I do have quite a few RLS patients who also
have migraine headaches and use triptans but none have reported any benefit for
their RLS when using that class of medication. Therefore, your response may be
quite unique to you (after posting this letter on our website we will see if
other RLS sufferers report similar benefit from triptans).
There are lots of treatment for RLS and in the hands of an RLS expert (that may be hard to find) you should have an excellent chance of finding relief from those symptoms.
Sent: Tuesday, June 07, 2011 2:35 PM
I have RLS 24/7 and take ropinirole (4 x 1mg) and tramadol medication.
I also take prednisone for Temporal Arteritis (diagnosed one year ago - started at 50 mg and now have reduced to 5 mg daily and still on reduction).
I have been dealing with insomnia for several years, worse since on the prednisone, indeed even when my RLS symptoms are well medicated I still have difficulty sleeping even though I am prescribed zopiclone 7.5 mg. Generally I fall asleep at around 1 am for about 2 hours, then I am up and awake for a couple of hours and then perhaps get another 90 minutes/2 hours sleep. This may vary by a half hour either way. On occasion I can go 48 hours without sleeping and even then when I eventually sleep it is for just the couple of hours.
Today my GP has suggested that I reduce the zopiclone to 3.75 mg for 2 weeks and then commence Circadin, which I understand is a slow release melatonin.
I know nothing about melatonin but have been advised by another RLS sufferer that melatonin would not be a good drug to take and that it is likely to badly affect my RLS symptoms as indicated in the links below.
http://www.journalsleep.org/Articles/280712.pdf and resulting in RLS.
I should be so grateful to hear from you with your views on this Circadin medication, and indeed if it is not suitable for use by someone with RLS, I would appreciate your views on what I could try next in place of the zopiclone. My GP has been happy to note your responding email on a previous occasion with regard to medication and RLS.
Not much is really known about melatonin and RLS. Only the first article below actually shows any possible relationship between taking melatonin pills and worsening RLS and that study was a very preliminary type of study with only 8 subjects.
We do not have Circadin here in the USA but we do have Rozerem which acts at least 8 times more potently on the melatonin receptors. I have used this on RLS patients without much if any worsening of RLS so far (does not mean that there is not a problem, just that I have not seen it yet).
I suspect that if there is an effect it wonít be all that bad and if so, you can just stop it. As melatonin works quite differently from zopiclone, you might ask your doctor about staying on the higher dose (unless there are other reasons to lower this dose) as that reduction will make your insomnia worse giving the melatonin less of a chance to be successful.
A Reply from Betty
Sent: Tuesday, June 07, 2011 8:47 PM
Subject: RE: Circadin
If I can just clarify. My doctor has suggested that I reduce the zopiclone to 3.75mg for two weeks and then stop the zopiclone altogether before starting the Circadin. Thus using only the Circadin to aid sleep.
Are you suggesting that I continue on the zopiclone at 7.5mg and add the Circadin to the zopiclone.
It would be nice if the Circadin would work alone but I find that the melatonin drugs often are not that potent when used alone. For patients with long term significant insomnia, I like to have all the firepower that I can use together (especially as they work in totally different ways) to achieve success. You can certainly try the Circadin alone and then add back the zopiclone if needed. All you have to lose is a bunch of sleep (if you can put up with that).
Sent: Tuesday, June 07, 2011 8:31 PM
Subject: thank you for the reply
I am from So. Cal and was diagnosed with RLS 8 years ago. My doctors have tried many meds, and I found the benzodiazepines to be the most useful. Mirapex is added when things get worse, but it (and especially Requip) cause vomiting even when taken with food. My insurance won't cover Lunesta as 30 pills cost $340 (COSTCO) to $400 depending on the pharmacy. So, my psychiatrist prescribed a regimen of alternating benzodiazepines at HS to avoid tolerance.
I'll gladly write my whole story for you.
I moved to an army job in Texas and the doctors here think I'm an addict to even ask for such meds. I'm back to anti-cholinergics again which make me much worse.
I search the literature and web and find there's a new campaign to discredit benzodiazepines completely. Please don't back down from your experience prescribing these medicines. For me, any of them work to nearly stop the agitation in the legs.
Sleepless pharmacist in Texas,
Stephen E., PharmD
I do prescribe lots of sleeping pills but I do try to stay away from the full
benzos like Xanax, Ativan, Valium, etc. If taken on a daily basis, they do have
a significant chance of causing tolerance/dependence (addiction is a different
story completely that implies abuse for non-medical reasons). However, if you
take the benzos on an intermittent basis (that does not include alternating
different benzos), tolerance and dependence can almost never occur.
The partial benzo agonist drugs (Ambien, Lunesta) have a much lower potential for tolerance/dependence and typically most patients can take these daily without much concern.
You stated that you were being given anti-cholinergics? They are not used for RLS nor do they affect RLS (good or bad) so I am wondering if you made an error here?
A Reply from Stephen
Sent: Tuesday, June 07, 2011 10:13 PM
Subject: which book is best for the clinical types?
I wonder what you advise for iron supplements? I take 325 mg of Ferrous sulfate daily and do NOT notice any irritation of the stomach even when it's empty. I find the full-benzos to be very helpful for my combination of sciatica and RLS. I usually do 5 days of an anti-cholinergic (calm the stomach) with Mirapex between different meds.
I find even Klonopin only sedates me for 8 hours and don't notice daytime
drowsiness to last anywhere near as long as the anti-cholinergic class. Also,
any lingering drowsiness is quickly cut with caffeine in the am. Going off them
is not a problem. I'm a tad irritable the next day, but I just take it easy. I
build tolerance to Ambien in 6 days and the Lunesta is still not covered even if
with calls to the insurer. I look forward to the day I can buy it.
Iron supplements are difficult as the higher your ferritin level (which hopefully will occur with oral iron therapy) the less iron you may absorb. Typically, when the ferritin level gets above 35 or so, the amount of iron that you absorb may be negligible (which means that you may be wasting your time pushing oral iron if you have no documentation that your serum ferritin is continuing to increase with these efforts.
Sent: Wednesday, June 08, 2011 5:57 AM
Subject: I Need Advice for coping with RLS
I am a 73 year old healthy female and have had restless legs for at least 40 years. I took Sinemet for about 3 years and I have taken Mirapex for about 8 years. For several months I have experienced an increase in symptoms. My doctor has determined that I am experiencing augmentation from long term use of Mirapex. He reduced my dose from .5 to .25 at 4:00 and 8:00 PM. This regimen did not work and he has said I must discontinue the Mirapex and not take anything for my RLS for 10 days. At that juncture he expects to reevaluate and determine what course of treatment is appropriate.
I am unable to sleep as I am unable to lie still. I cannot do anything productive involving sitting. I stand and walk around to read. I rode the bike during the night and enjoyed relief for about 15 minutes each time. I walk during the day, but none of the usual exercises seem to be working. I am desperate for help. I have checked on Clinical trials, but NIH does not have any research protocols for which I qualify.
Your doctor deserves kudos for realizing that you are developing augmentation
from Mirapex (most doctors would have no clue about this problem and that
includes many specialists who treat RLS). He is also somewhat correct that
stopping Mirapex is a reasonable treatment for augmentation. If you were on a
lower dose, increasing the dose may be reasonable but an increase in dose now
would likely result in an increase in symptoms within the next several weeks or
The problem with decreasing your Mirapex or discontinuing it (as you have already found out) is that the RLS markedly increases with reduction or elimination (you donít want to even know how bad it can get compared to what you are experiencing already) of Mirapex. What we normally do at this point is add a potent opioid (methadone, oxycodone) to treat the increase in RLS symptoms while getting off Mirapex.
After a few weeks off Mirapex, your RLS symptoms will decrease so that you may be able to switch over to anticonvulsants (gabapentin, Lyrica or the soon to be available Horizant) which may be able to handle your RLS symptoms. There is no reason to suffer as the therapy outlined above will make this transition very smooth and easy.
It may be helpful to get a copy of my book for patients, RLS: Coping with your sleepless nights (profits from this book go to the RLS Foundation). You may also consider getting my book for doctors, Clinical Management of Restless Legs Syndrome to help guide your doctor on how to treat your RLS problems.
It typically takes a week or two until the RLS calms down after stopping a dopamine agonist so you may be lucky if it is getting better this quickly. Even though the oxycodone is the correct treatment, you should let you doctor know what you are doing. You may need more of the drug and if so oxycodone without acetaminophen (Tylenol which is included in your generic Percocet ) would be a better choice as the acetaminophen does not help RLS. Methadone works even better but if you are doing well with oxycodone just stay on that drug.
Sent: Thursday, June 09, 2011 4:27 PM
Subject: Neurofeedback treatment
I'm 53 years old, have been on many medication combinations, and was diagnosed "Quiescegenic Nocturnal Dyskinesia" by the John Hopkins Clinic.
Do you know of patients that have been treated effectively with Neurofeedback? Is there a specific RLS protocol?
There is not that much known about Quiescegenic Nocturnal Dyskinesia as this
has only been described by Richard Allen's group at Johns Hopkins in a letter to
the editor in 2009. We are still not sure whether is indeed a real syndrome or
simply a variant of RLS. Dr. Allen may have more information about treating it
and since you have already been there it is likely that you have received some
ideas about treating it.
Biofeedback/neurofeedback has been looked at briefly for RLS and has not demonstrated any benefit. Perhaps with better studies this may change but at this time we cannot recommend that modality of therapy for RLS.
Sent: Friday, June 10, 2011 7:46 PM
Subject: Hylands "Restlful Legs" Homeopathic
I spotted this Homeopathic treatment for "Restful Legs" at
a local CVS drugstore.
Have you had any success using this combination or any of its ingredients for RLS or PLMS? The CVS Pharmacist recommended Pusatilla.
One can never say that a remedy absolutely wonít work but there are no ingredients in this preparation that have ever been shown to help RLS. If it was a good product and really helped RLS patients you would not have to ask about as everyone would be talking about how good it is. Check the forums and I doubt that you will hear many (if any really ones).
A Reply from Steve
Sent: Saturday, June 11, 2011 7:37 AM
Subject: Re: Hylands "Restlful Legs" Homeopathic
Thanks very much. I agree. At first glance, it seemed too good to be true. Hyland appears to be taking advantage of the recent publicity and advertising for FDA approved RLS medications.
A few years ago, I tried Valarian Root at various doses. In my case (PLMS with mild night time RLS), it did not help me sleep through the night.
Currently, I take temazepam, gabapentin and Lyrica, all at bedtime. There seems to be some half-life side effects that extend into the next day, but they are manageable.
Sometimes, I go for a short run, a bike ride or engage on some physical activity to "wake up". The running or activity - along with the adrenaline/endorphin surge, seems to move the meds out of my system a bit faster. In any case, its a healthy habit.
It is unusual for patients to take gabapentin and Lyrica together as they both work on the same receptors in the brain. Gabapentin is a very unpredictable drug due to poor absorption which decreases as one increases the dose. Lyrica is much better and normally I have my patients stick with that drug over gabapentin.
A Reply from Steve
Sent: Saturday, June 11, 2011 1:16 PM
Subject: Re: Hylands "Restlful Legs" Homeopathic
Gabapentin worked very well for me for awhile, then started to lose its effectiveness over the next few years. I think the reason the Gabapentin helps me now is one of its side effects (drowsiness) helps me sleep through the night. I have sometimes awakened during a PLMS "urge to move" symptom. In my case, the urge is much more intense than ANY early evening RLS symptom I have experienced. I would say my PLMS is pretty severe. The Lyrica helps, but I am limited on the dose I can take (600 mg).
I have not tried Lamictal or Zonegran yet. Last time I looked, there was a very small preliminary study on Zonegran (about 15 participants) that indicated a high success rate. When I participated in a Johns Hopkins study in Baltimore, the Neurologist mentioned Lamictal as a good choice.
At the time, JH was getting promising results from an iron infusion therapy study. I had heard about that and was taking multi-vitamins plus iron to see if it would help. The added iron did not seem to make any difference. However, the effect may have been so gradual, I may have missed it. When I tried to participate in a double-blind JH iron-infusion study, they said my iron level, at the time, disqualified me from participation. Also, JH believed my iron was a bit on the high side medically and recommended I cut back on the iron supplements. I followed their advice.
Are there any studies available for Lamictal or Zonegran ? I am under the impression that Gabapentin, Lamictal and Zonegran all act on the same brain receptors and act pretty much the same.
None of those anticonvulsants have great studies demonstrating that they are effective for RLS. However, many of us do use any and all of these drugs for our tough RLS patients that do not respond to the more commonly used anticonvulsants. It is always worth a try. Lamictal and Zonegran do not act on the same receptors as do gabapentin and Lyrica but there is some overlap.
Sent: Sunday, June 12, 2011 5:20 PM
I have had RLS since I was a child, it would come and go, I'm now 44 and it is worse than ever. I have been to a neurologist. Tried all the classic meds. Now, the only relief is to hit it with 2 Percocet. So I take 2 during the day and 2 about 2 hours before bed time, or when I feel it starting. It's been working for a few nights now. I can't express how awful this is. I hate having to take this medication as it loops me out but I simply cannot sleep, watch TV, sit at the computer, or anything, without it.
I sure hope this isn't how it's gonna be for the rest of my life. If anyone has any different input, I'll gladly read it. I have already tried: Requip, Mirapex, Gabapentin, Sinemet, Ultram, Lorazepam, Homeopathic Restful Legs and Leg Cramp meds, iron, bananas, and tonic water with quinine.
I would not come close to giving up or resigning yourself
to suffering just yet. Most RLS sufferers can find very good relief with proper
therapy. Finding a doctor to prescribe that therapy is the difficult part.
Percocet typically works well to relieve RLS symptoms but it is a short acting drug which is why you need to take so many pills and it contains acetaminophen (Tylenol) which does not help RLS. There are better opioids available.
Often one drug may not help but combination therapy with drugs that you may have already tried (or similar ones) may often work even better.
Sent: Wednesday, June 15, 2011 8:45 AM
I am a white female aged 69 who has suffered from rls for many years. It is difficult to determine when it started as it started out mildly and has progressed over the years until I was not getting much more than 4 or 5 hours of sleep each night. ( I suffered every night!) I remember that I started losing a lot of sleep before 1990, prior to that although it interfered with my sleep, it wasn't a big problem. My father suffered from it but I do not know to what extent. My sister (64) has it but she tells me that it has subsided - she has not taken anything for it.
I have spent quite a bit of money and have tried everything I have ever heard about to no avail with the exception of pharmaceuticals which I didn't want to start.
The things I tried that I can remember:
acupuncture - at least 10 treatments
bar of soap under the sheets.
I have been living for the last ten years in Mexico and have smoked marijuana nightly which helped me fall asleep but after a few hours my legs would wake me up and I had to smoke some more.
About a month ago a friend told me she also had rls and a doctor recommended a drug here called Tasedan (estazolam). It is quite inexpensive (60 2 mg for about $20 U.S.) A retired pharmacist checked this drug out for me as anything I found about it in my internet research was in Spanish. He informed me that he thought it a safe drug for me and I believe he said it was a form of valium.
I started taking one pill before bedtime and the results have been incredible!
I am actually getting 8 (or more) hours sleep each night, I wake up well rested and refreshed and for some reason I have either started to dream or I am remembering my dreams (no nightmares).
My whole outlook on life has improved. I smile a whole lot more, I have more energy. I have always loved living here in Mexico but since I have been sleeping I appreciate it even more!
I asked my husband if he noticed a difference in me and he replied "Yes, you're talking a whole lot more!! I find myself gabbing on the phone with friends now when a month ago I seldom had more than a 5 minute conversation.
When I move here I began to lose weight - no diet or anything I can attribute it to. I went from a size 14 to a size 6. I am not happy about the weight loss as I think I looked better with a bit more weight. I went to my doctor just to make sure there wasn't something wrong, but after extensive testing he said I was in great health.
In the last month I have happily gained 2 pounds, I hope to gain at least 8 more.
Friends have commented about how I look better (sleep, not weight gain).
I had regularly searched the internet websites for RLS and tried just about every suggestion (except pharmaceuticals) to no avail, I had not found this medicine (yes, it's a pharmaceutical ) listed. Now hopefully someone will get some benefit from my discovery.
My whole life has changed dramatically.
Estazolam (brand name is Prosom) is a well known sleeping
pill that acts upon the benzodiazepine receptors (the same as Valium) and is a
reasonable drug to use to help promote sleep. This drug is actually listed and
described on our RLS Treatment Page.
The drug does not treat RLS but just keeps RLS patients asleep (just like back pain, if you are asleep, you have no pain).
However, you should take care with this drug as daily use may lead to dependence and tolerance. It is much safer when used only 3-5 times per week.
A Reply from Ellie
Sent: Wednesday, June 15, 2011 6:55 PM
Subject: Re: RLS
I appreciate your concern but I believe taking these pills is preferable to smoking marijuana nightly and since my legs keep (kept) me awake every night - all night long - I shall continue to take them as I truly believe they cause much less harm than the other pharmaceuticals on the market for rls. I already am dependent on them for sleep for without them I suffer.
I really believe they have relieved my RLS symptoms - I still awaken during the night on occasion to use the bathroom, or when I hear the rain and I get up to shut the windows, it does not! put me in a coma like state.
I tried the sleeping Ambient (sorry - don't know the correct spelling or name) and although it put me to sleep, my legs continued to jump the entire night waking me up but I was unable to deal with them as I was too drowsy.
I am now getting 8 hours of refreshing sleep and my whole personality has perked up. I am more talkative, animated, happy, fun to be with. I am beginning to believe that my legs kept me from having enough dreams and if one does not or can not dream it has a very bad effect on your mind.
But, as I said, thanks for you concern.
Sweet dreams to you!
Sent: Wednesday, June 15, 2011 10:01 AM
Subject: CCSVI for RLS?
I was wondering your feelings on if there would be a connection or help with this CCSVI trial program for ms patients out there and maybe helping RLS patients I guess they put a stint in the carotid artery and the opening up of blood flow from heart to brain has helped with energy foot drop etc for MS patients but several of the ms patients helped had RLS symptoms and they no longer had symptoms after the surgery. I wondered what your opinion might be or if there would be no connection?
Actually, I am quite familiar with the CCSVI trials for MS.
The stent (or angioplasty) is done on a vein (jugular or others) not an artery
like the carotid. I have had one of my patients (not with RLS) undergo this
treatment with minimal improvement. There is an increase in RLS with patients
who have MS but this is also quite common with many other neurological
As we cannot even be sure that CCSVI helps MS, it is really impossible to speculate whether it would benefit RLS patients (my guess would be no).
Sent: Thursday, June 16, 2011 4:37 AM
Subject: A TSH question
I have had RLS for several years. It keep progressing. I just learned that my recent TSH level was 5.5. This is considered only slightly elevated & thus not requiring treatment.
However, I've read that the normal limits for TSH were based on a population that included people with mild hypothyroidism, and thus a more reasonable upper limit for wnl should be around 3. I don't know what my free T4 is (trying to get that info). It was supposedly within normal limits.
What is your view on the possibility of a TSH of 5.5 affecting my RLS?
There is a small increase in RLS amongst thyroid disorders
but there is very little research on this issue and we have no idea if it
related to the severity of the problem.
However, you are correct about the borderline value of your TSH level and likely your T4 levels will be normal (which means that there are no physiological consequences to this problem yet). Also, since you already have RLS, there really is no impact of having additional thyroid problems as the studies just demonstrate that RLS is more common with thyroid problems.
The information and advice on RLS given on this web site is for educational purposes only. None of the advice, information or medical treatments should be followed without the supervision of your medical provider. The information presented on this site is not a substitute for your doctor, but should be used to help you discuss your RLS problem with your doctor. Do not undertake RLS medication treatment on your own! Please seek qualified professional medical care to help treat your RLS symptoms.
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