Why RLS and PLMs Get Worse With Treatment

[Muffy]

A bunch of stuff arranged in similar fashion to the way I organize my garage:

http://www.rls.org/Document.Doc?id=1706

http://www.movementdisorders.org/UserFiles/RLSsm004.doc

http://www.movementdisorders.org/UserFi ... m003-1.doc

http://www.movementdisorders.org/public ... tofrls.pdf

"Rebound and Augmentation in RLS: Reports in the literature indicate treatment of RLS with dopaminergic medications can result in a shifting of symptoms to the early morning hours, referred to as rebound. Rebound was not reported in the clinical trials of MIRAPEX tablets but the trials were generally not of sufficient duration to capture this phenomenon. Augmentation has also been described during therapy for RLS. Augmentation refers to the earlier onset of symptoms in the evening (or even the afternoon), increase in symptoms, and spread of symptoms to involve other extremities. In a controlled trial of MIRAPEX tablets for RLS, approximately 20% of both the MIRAPEX- and placebo-treated patients reported at least a 2-hour earlier onset of symptoms during the day by the end of 3 months of treatment. The frequency and severity of augmentation and/or rebound after longer-term use of MIRAPEX tablets and the appropriate management of these events have not been adequately evaluated in controlled clinical trials." (Mirapex package insert)

No evidence of augmentation with rotigotine treatment in a 6-month, multicenter, double blind, placebo-controlled RLS trial W.A. Hening, R. Allen, J.W. Winkelman, E. Schollmayer (Piscataway, NJ)

http://www.emea.europa.eu/humandocs/PDF ... -19-AR.pdf

Anne-Marie Williams and Diego Garcia-Borreguero Current Treatment Options in Neurology 2009, 11(5):327–332 Management of restless legs syndrome augmentation

Muffy

[roster]

Thanks Muffy, from the both of us!

[kteague]

Hey, I resemble those reports! Thanks for the reading, Muffy. I scanned them and now have to go back and try to digest them. Having been on 3 of the meds discussed - Sinemet, Mirapex, and Requip - the topic is of great interest to me. Is the info in these RLS studies parallel to those being treated for the diagnosis of PLMD?

[Muffy]

I certainly think so, but I don't think we're going to find the same amount of evidence since one needs PSG to show that vs just history in the case of RLS.

Muffy

[katherinefulmer]

Thanks Muffy! Your post on RLS has been added to the CPAP Wiki:

wiki/index.php/Restless_Leg_Syndrome

[SaltLakeJan]

sHi Muffy,
Thanks for the articles, I have spent the last couple of hours reading "The Treatment of RLS, an Evidence Based Review.
I'd hate to take a test on what I learned. I did concentrate on the drugs that I use. Pramipexol .075 mg, and Pregabalin 150 mg, and Tramadol 50 mg. I also read about iron deficiency, since my Ferritin level is 7. My Gasteroenterologist had me swallow the Capsule to determine where I am losing blood. Everyother part had been tested & retested. The pictures from the Capsule determined it is in the lower stomach. He started Ferrous Glauconite 324 bid for a month trial. I go back to him in a few days for further testing

Last spring the Mirapex was reduced from 3.0 mg to 0.75, & Lyrica from 300 mg to 150 mg. I have wondered if that reduction has any connection to the 846 PLM's discovered in my June Sleep Test?

From what I read Mirapex and Lyrica are effective treatments for the present. I do sleep without leg problems, that I know of, as long as I take both drugs. But, now that I know that RLS & PLM's will get worse with treatment, I am concerned. I didn't know that when I last talked with my Sleep Dr. I did ask him if those were the drugs he wanted me to be on for long range treatment. Since my sleep study he has wanted to increase the Mirapex and he wanted me to get enough Hydrocodone that I could sleep through any movements. He did not want to prescribe it, and I didn't try to get it. I make enough booboo's in ordinary conditions, no counting what I would do on daily opiates. I did ask my pcp what he would suggest, he gave me 50 mg Tramadol, and I take it at night.

Muffy, I will continue to read the articles. I appreciate you sending them for those of us who have RLS & PLM's. I am at a loss to know what to do. Do you have any thoughts or direction that would help with this?

Hope you have an enjoyable Thanksgiving. Are you cooking this year? DH & I are going to our daughter's. There will be lots of excited little kids there. So many in fact, that DH & I may just slip out early.

It was good to "see" you again.

Jan



Jan

[kteague]

Jan - 846PLM's in your sleep study?????? Mercy!!!!!!!!!

[rested gal]

Very interesting, Muffy.

Thank you. You're a good'un.

[-SWS]

Another reader following along...

So thanks from me as well.




For new readers who also happen to be following along:
http://my.clevelandclinic.org/disorders ... order.aspx

What is periodic limb movement disorder (PLMD)?

Periodic limb movement disorder (PLMD) is a condition that was formerly called sleep myoclonus or nocturnal myoclonus. It is described as repetitive limb movements that occur during sleep and cause sleep disruption. The limb movements usually involve the lower extremities, consisting of extension of the big toe and flexion of the ankle, the knee, and the hip. In some patients, the limb movements can occur in the upper extremities as well.

The limb movements occur most frequently in light non-REM sleep. The repetitive movements are separated by fairly regular intervals of 5 to 90 seconds. There can be significant night-to-night variability to the frequency of limb movements.



What causes PLMD?

The exact cause of PLMD is unknown. However, several medications are known to make PLMD worse. These medications include some antidepressants, antihistamines, and some antipsychotics.

Many individuals have periodic limb movements in sleep (PLMS). This is observed in about 80 percent of patients with restless legs syndrome (RLS). PLMS can occur in over 30 percent of people aged 65 and older and can be asymptomatic. PLMS are very common in patients with narcolepsy, REM behavior disorder, and Parkinson's disease.

True PLMD -- the diagnosis of which requires periodic limb movements in sleep that disrupt sleep and are not accounted for by another primary sleep disorder including RLS -- is uncommon.

[Muffy]

Hi Muffy

Hi back!

But, now that I know that RLS & PLM's will get worse with treatment...

Not necessarily "will", but certainly "can".

There's an almost endless list of combinations and permutations, including:

Is the disease entity PLMs, RLS or a combination of both
Are they severe enough to be treated
Choice of drugs
When the drugs are taken
Ability to monitor therapy (RLS = easy to monitor. It's there or it ain't. PLMs = without PSG or actigraphy, not so easy.)
Time.

I am concerned.

I think it is more important to be "aware" rather than "concerned", and consider changes to the treatment plan if things aren't going well. This is a great document on dealing with pesky ("refractory") RLS:

http://www.rls.org/Document.Doc?&id=1296

Muffy

[kteague]

Hmmmmm. Lots to read. Just thinking that I spent a few years on Neurontin I think while on Sinemet and also for a while on Mirapex. Also been on Tramadol for a couple years, though not regularly. I'm getting pretty far down the list of options, and the ones yet to try I have reservations about. What's a lady to do?!

[Muffy]

Well, I thought the idea of the 24-hour rotigotine transdermal patch could be a pretty clever strategy in terms of keeping the RLS where it is:

No evidence of augmentation with rotigotine treatment in a 6-month, multicenter, double blind, placebo-controlled RLS trial W.A. Hening, R. Allen, J.W. Winkelman, E. Schollmayer (Piscataway, NJ)

http://www.mdconsult.com/das/citation/b ... e_id=22071

http://www.clinicalstudyresults.org/doc ... 4623_0.pdf

http://www.ncbi.nlm.nih.gov/pubmed/1755 ... t=Abstract

and perhaps offering coverage for night-long PLMs (which I imagine is the case if you have 846 of them). However, there were instances where the product broke down and got recalled:

http://www.neupro.com/Home/Home.asp

But the rumor mill says it should be back "soon".

Also, keep in mind that even 846 PLMs might not be bad if they don't cause sleep disruption, as evidenced by the PLM Arousal Index.

Muffy

[SaltLakeJan]

Hi SWS,
It was a pleasant surprise to hear from you and Muffy. And, I welcomed all the material on RLS, and PLMD. It came on a timely basis. I have a pending appointment with my Sleep Dr., and the articles from you and Muffy, will give me informed questions to ask. Last July, he said he would schedule a sleep test this coming January. When I called to check on my appointment his Secretary said he had an office appointment scheduled, but nothing else. If he isn't going to test me, I am considering a doctor at the U of Utah sleep medicine facility. They are an ASMA approved sleep center.

I suspect the PLM's are still with me. I won't know without a psg or actigraph. I fit the description in the Cleveland Article of nonrestorative sleep, excessive daytime fatigue and sleepiness. It is strange because I sleep about 9 hours each night.I haven't had any new meds that would cause those symptoms, however for the first time in my adult life I am falling asleep at inopportune times. My Opthomologist paused during an eye exam, & I fell asleep. I've also fallen asleep in meetings and church. it doesn't happen every day or every appointment, but I need an answer. It is also very embarrassing.

Thanks again for the article. It explained the treatments and the PLMS & RLS so clearly, I could understand most of them.

Wishing you an enjoyable Thanksgiving. Jan

[SaltLakeJan]

Hi Muffy,
I agree with your assement of the document you sent, it is excellent. Thanks for sending it and for your comments to be aware not concerned. Table 8 in the document gave an easy to understand explanation of rebound and augmentation.
It makes it much easier to be aware - now that I have a better understanding of rebound and augmentation.

It also included information about treatment of low Ferritin, and that it can be a factor in RLS & PLM's. My Gastro. Dr. has known me for years and told me if the Ferritin levels didn't increase, he would treat it aggressively. I am taking the article to him regarding the iron sucrose infusion that failed in a double blind study. I would be relieved if treatment for low Ferritin would eliminate the two problems.

RSL is a familial condition in my family. Mine requires treatment, but I consider it moderate. My two daughters and some of my grandchildren have a stronger form. They jiggle their legs day and night. However, the girls say they are used to it, and will get treatment when it begins to bug them. I don't know when My PLM's began, or if they are connected to RLS.
I wrote to SWS saying that I suspect the PLM's are active because of my symptoms. I plan to take this up with my Sleep Doctor, if he is willing to respond this time.

I read in the article that the only non-dopaminergic agent to cause augmentation is Tramadol as low as 50 mg. Muffy, I can do without this. Would a general recommendation be to stop the Tramadol?

I was so pleased & relieved to get all the information for PLM's & RLS. Without it, it would have been difficult to tell my sleep doctor about my specific concerns, because all I could have told him is that I can't ignore this, any longer. I have told him several times about my fatigue and daytime sleepiness. He attributes it to Cpap Therapy. Could he be right?

Appreciate you guiding me in the right direction. Jan

[Muffy]

I plan to take this up with my Sleep Doctor, if he is willing to respond this time.

Did you complete this worksheet? Also put in ferritin levels where/when you have them.

viewtopic.php?f=1&t=41392&p=383172&hili ... sg#p383172

Would a general recommendation be to stop the Tramadol?

A general recommendation would be not to give general recommendations about taking/discontinuing medications.

I have told him several times about my fatigue and daytime sleepiness. He attributes it to Cpap Therapy. Could he be right?

I think one has to be absolutely clear on this point, but arguably, if CPAP creates more problems that it solves, then you really have to consider a different question.

Muffy