Restless Legs Syndrome (RLS) Discussion Board

Dipyridamole was used successfully in a small trial by a research group. The paper is in the research section. My internist has okayed my trying dipyridamole to see if it helps my restless legs symptoms. The clinical trial participants noted improvement in restless leg symptoms, sleep, and PMLS.

One problem is that the trial description was very sketchy and did not discuss the dosage used. The most common side effects of dipyridamole are dizziness due to low blood pressure, and headaches at the initiation of treatment. Common dosages used in the past for post-stroke recurrence prevention are in the range of 150 to 400 mg daily, in divided doses.

I already take high blood pressure medicine so need to be especially careful about having my blood pressure go too low, I am planning to start out at 18 mg four times daily.

For the time being I am going to continue my regular medication regimen for restless leg syndrome. That is, at 7:30 in the evening I take 0.125 mg Mirapex (pramipexole), 100 mg gabapentin, 15 mg THC as edible marijuana, and 720 mg of kratom. Approximately 3 or 4 hours later I also take gabapentin 50 mg, kratom 360 mg, and THC 5 mg. This regimen provides good control of restless leg symptoms, primarily I have a little bit of jumping legs from about 5 p.m. to 8 p.m. The main problem I have with this current regimen is that I am tired in the day, presumably due to chronic sleep deprivation. I do sleep 7 hours or more per night but don't get much deep sleep. Also the impulse control problems with Mirapex, and possibly RLS, make it so that I am much less productive than I was several years ago, having a greater tendency to just kind of sit around and watch TV or similar activities.

So my goals with trying a different treatment are improvement in impulse control and better refreshing sleep. I am hopeful that I can cut the dose of Mirapex down from what I currently take, possibly even stop it altogether. It would also be nice to cut down the gabapentin if I could.

I will update as my experience proceeds.

I hope this works well for you. We will be eager to see how things go.

Looking forward to the results!

This regimen provides good control of restless leg symptoms, primarily I have a little bit of jumping legs from about 5 p.m. to 8 p.m. The main problem I have with this current regimen is that I am tired in the day, presumably due to chronic sleep deprivation. I do sleep 7 hours or more per night but don't get much deep sleep.

I had (have?) the same problem, and deal with it in what I used to think was the worst way possible - by adding another medication. If I don't take modafinil, I notice by noon that I am unbearably sleepy, and I get nothing accomplished for the rest of the day. It can't be healthy - it just can't - to make up for sleep loss with a chemical. I too am very interested in your experiment.

After some leads given to me by Steve, and several phone calls, I talked to one of the researchers involved in the dipyridamole study. The dose of dipyridamole used was 100 mg at 8 p.m. to start and increased as necessary to 200 then 400 mg daily. A separate paper is due to be published soon with the details of the dipyridamole clinical experiment. I have 75 mg tablets and took 1/4 every 6 hours starting last night without a problem. I think I'll take 75mg at 7:30 with my regular meds tonight. Thanks Steve.

I should point out for those unfamiliar with United States medical treatment and research studies that my attempts to treat my RLS with dipyridamole is definitely NOT standard of care and NOT approved by the FDA or other medical sources. This is an experiment by me to see if this may help me, and I do not recommend anyone else try this.

I am a retired MD so have additional knowledge that most of the other readers of this forum do not have, additionally I have a very helpful and agreeable internist who is willing to prescribe medication for me as long as she feels that it is not likely to be unnecessarily dangerous.

This experiment by me is fraught with lots of variables, unknown risks, and unknown benefits. It is extremely unlikely that any of the readers of these forums would be likely to persuade their doctor to prescribe dipyridamole for them.

Holland, did Sergei give you any idea where the paper will be published?

It has been submitted, waiting on approval. I didn't ask which journal.

I have now taken dipyridamole for the last 3 nights, the first two were basically just test doses to be sure I didn't have any obvious serious side effects.

Last night I substituted 150mg dipyridamole for my usual 0.125 mg mirapex. Differences from my usual good control of leg jumping are that I had much more leg jumping from approximately 8:15 p.m. to 8:45 p.m. than I usually do. However by 9:15 urge to move had resolved and when I went to bed at 9:15 I had no urge to move symptoms. I did not fall asleep immediately which is not uncommon although not the usual situation for me. By about 10 p.m. mild urge to move symptoms had returned, and I decided to take an additional 75 mg dipyridamole. That improved urge to move symptoms but did not resolve them. I ended up having a poor sleep night compared to my usual routine, not unexpected as I anticipate dose adjustment to be necessary. I slept in bits and pieces until about 3 a.m., then slept until 5:30 am.

It is remarkable that I got any sleep at all considering I took no mirapex last night, the first night in 2 years that I didn't take mirapex. Main side effect of dipyridamole I noticed is mild dull headache and occasional mild lightheadedness on quick standing. BP dropped to as low as 105 over 70. I will be cutting the dose of my blood pressure medication to decrease the risk of lightheadedness and falls.

My initial conclusions are that the 225 mg dose of dipyridamole I took has a definite effect on urge to move, however I probably need a higher dose of dipyridamole.

To increase the likelihood that I get a better nights sleep tonight, I am anticipating taking 225 mg dipyridamole at 7:30 and 0.0625 mg of mirapex. That would be half of my usual dose of mirapex. I will continue my usual doses of THC, Kratom and Gabapentin.

Holland, the mere fact that you got any sleep at all is wonderful since otherwise you would have been going through DA withdrawal, i.e. no sleep at all.

As for your low blood pressure, welcome to my world. Lightheadedness from a BP of 105 over 70 is what I have had to live with for all my life. Whenever I have complained about it to my GP, especially after fainting a couple of times, I always go a line about be glad you have it. Easy to say when you aren't the one with the concussion from hitting your head when you passed out.

So, thanks for doing this for us and I really, really hope it continues to work. The way things are going, we are going need another mode of treatment sometime soon.

I had an absolutely terrible thought last night about what might happen if full scale clinical trials show that dipyridamole is an effective treatment for RLS. This is based upon a med that my wife tried for her MS a couple of years ago. It used to be that there was a drug that was used to treat psoriasis. The chemical compound is dimethyl fumerate. The chemical was so cheap that an industrial purity product was used as a flame retardant for furniture until lots of people were reporting rashes from it.

Well, this product was found to be the first safe oral medication that was an effective treatment for MS. There had been a couple of others, but they had an unacceptable frequency of fatal side effects. So what happened? One of the drug companies bought up all the patents and generic supplies for the psoriasis drug and then took it off the market. They tweaked the formula to make it extended release and then released it as an MS med. The cost of the industrial chemical is about $5/lb and the old psoriasis med was typical of the cost for generics. The current cost for just a one month supply of the new med is over $5K. For my wife, took it for two months. It worked great for a couple of weeks and then totally lost effectiveness. We have since been told that her experience was not unusual.

So, my fear is that if it works, some company is going to do the same thing to dipyridamole, raise the cost to astronomical levels and then market it to those of us with refractory RLS as a "safe" alternative to opioids.

Rustsmith wrote: ...So, my fear is that if it works, some company is going to do the same thing to dipyridamole, raise the cost to astronomical levels and then market it to those of us with refractory RLS as a "safe" alternative to opioids.

That's possible, however it's still not at all clear how effective dipyridamole use is for people with RLS. The paper on adenosine and dipyridamole suggests that the results are best used as a springboard for developing new medications that affect adenosine, but don't have the other problems of dipyridamole. One thing I don't understand is they talk about the problem of dipyridamole not crossing the blood-brain barrier, however how can it work if it doesn't cross the blood-brain barrier?

My test prescription for dipyridamole for 60 tablets at 75mg, cost me $74 at Costco. Seems a little high for a generic that's been out for years. Possibly the price reflects the fact that it's not used very much orally.

Developing a long-acting form of dipyridamole and getting FDA approval will require a clinical studies, expensive. It would be only somewhat more expensive probably to develop a new medication that has fewer side effects.

Short report on fourth night of dipyridamole. I took took 225 mg of dipyridamole at 7:30 p.m., in addition to half of my regular dose of mirapex. I also took my regular doses of THC, gabapentin and kratom. Like the night before, I had an episode of marked urge to move from approximately 8 - 8:30 pm. Similarly, by the time I went to bed about 9:15, urge to move had completely resolved. I slept well for the next 7 hours, no further episodes of urge to move.

I did have a mild headache, better than the night before, and mild nausea for about half an hour before bed. No significant standing lightheadedness.

I'm thinking I will probably repeat that for the next couple of days before making any further adjustments to see how stable my symptoms are.

I reread the Pivotal role of Adenosine paper. I understand quite a bit more now than I did initially, probably I understand 10% now. LOL. At any rate, the article clearly says that adenosine is an important mediator of sleepiness. I am thinking that once I get a single dose in the evening optimized that I will try adding some daytime doses as well, since daytime sleepiness is a big problem for me. It also says that Gabapentin mediates the glutamate path which is crucial to hyperarousal. The dopamine agonists mediate the dopaminergic path which controls leg jumping but has no effect on hyperarousal. This is an important concept for the many people who have their leg jumping controlled by a dopamine agonist but still have trouble sleeping. Someone please correct me if I am reading this incorrectly. I wonder how many of those that take opioids alone would sleep better if they added a small dose of Gabapentin.

Holland, that exactly summarizes my understanding of what the paper said. All this info is all fairly recent, not just the adenosine. The preliminary report of glutamates role in RLS was only published by Dr Allen a couple of years ago and the formal paper was maybe about one year back. So, the roles of dopamine and glutamate are things that only the experts who read the RLS literature would be aware of. I agree that I have wondered how many would benefit from combined therapy of gabapentin+?? rather than the monotherapy of just dopamine, gabapentin/Horizant/Lyrica or an opioid. It also raises questions in my mind about the effectiveness of gabapentin/Horizant/Lyrica monotherapy for those with significant movement issues.