Dipyridamole didn't work for me

[707twitcher]

I was hoping to be able to come off buprenorphine so that my digestive system could return to normal, and was excited to learn about dipyridamole on this site. Several studies show that it is effective for RLS. I started with 75mg night one, then 150, and 225mg on night 3. I removed my buprenorphine patch the morning of Day 3. First night without buprenorphine was fine, other than the headaches which started immediately with first pill. I apparently had enough buprenorphine in my system from the patch to get me through that night. Second day without buprenorphine was hell. It started around noon with RLS symptoms in my shoulders, back and arms. This continued and intensified (and spread to the legs as well) - it was probably the worst RLS episode I've ever had. I took 225mg of dipyridamole at 5pm, stuck it out til 8pm hoping it would kick in, but finally took some sublingual buprenorphine. I had to take about .65mg, which is more than I've ever taken, and I still had hints of RLS all night. Also had one of the worst headaches ever that afternoon/night. I gave it one more try last night - 225mg at 7pm. RLS started when I went to bed at 10, so back to buprenorphine sublingual. At least .4mg (my normal dose before I switched to the patch) worked well again. So I'm done with dipyridamole.

The experience made me wonder though.... Was my awful RLS episode reflective of my normal baseline RLS without medication (since I stopped buprenorphine the previous day)? Or was it exacerbated by withdrawal symptoms from stopping the buprenorphine? From what I've read, buprenorphine withdrawal should take at least a couple days to hit, and all the discussion about it focuses on people taking it to help with opioid withdrawal at much higher doses. So I think withdrawal is highly unlikely. I suppose a third option is that the dipyridamole made my RLS worse, but that seems unlikely as well.

A few thoughts about this experience showing me what my medication-free RLS symptoms are like:

1. I couldn't make it through the night without buprenorphine. I fully understand people contemplating suicide over RLS symptoms. I would have been at that point later that night without drugs.

2. If my 12 years on pramipexole, with augmentation happening for the final 6 months, worsened my symptoms to this point, and this is now 4 months post-pramipexole, is this indicative of my underlying RLS baseline, or might it improve eventually after more time off pramipexole? Maybe I was augmenting for far longer than the last 6 months on pramipexole - the underlying RLS was getting worse (more intolerable symptoms), but this wasn't ever noticed because the DA was keeping symptoms at bay.

3. My symptoms felt intolerable, and yet they are completely under control with a relatively low dose of buprenorphine (.4mg sublingual or 7.5mcg on the patch). I assume that this means the dose of opioid or other medication (gabapentine/pregabalin) required to bring relief is not necessarily driven by severity of symptoms. More likely just individual differences in how we respond to drugs.

4. The standard advice for weaning off DAs only mentions using opioids as a last resort. I don't know how I could survive one night, let alone a few months, of no DA (or reduced dose)and no opioid. I'm generally fairly pain-tolerant, but maybe I'm a real baby when it comes to RLS. I never missed a night of pramipexole during the 12 years I took it, and I was always able to eliminate symptoms when they did arise with a little more medication. So I've not had to endure a full night of bad RLS ever. Even when I weaned off pramipexole, buprenorphine enabled me to do so without having any bad nights. I really sympathize with people who endure this without drugs. I could not handle it.

Sorry to ramble on.....

[ChrisColumbus]

I note that the positive Garcia-Borreguero study into dipyridamole published in 2021 stated that "its usefulness in patients resistant to dopamine agonists or patients undergoing augmentation needs to be determined". I haven't as yet found a study confirming effectiveness in patients who previously augmented on DAs, but I've only done a quick search. SueJohnson : I know that you've probably read most about dipyridamole - have you seen a follow up on post-augmentation trials?

[SueJohnson in reply to ChrisColumbus]

no

[Joolsg]

It is difficult. Dr Earley ,at Johns Hopkins University, insists all his RLS patients go completely med free for 2 weeks after going through dopamine agonist withdrawal.

That is to reset dopamine receptors and ascertain base line RLS.

So. You would have to stick out 2 weeks without ANY meds to see what your RLS is really like. Only the strongest patients can achieve this as the physical and mental torture would be unbearable. I just about managed the withdrawal from Ropinirole without meds!

It's a shame dipyradimole didn't help, but perhaps it might work for someone who manages to get through the 2 week med free washout period.

[707twitcher in reply to Joolsg]

Thanks. If I didn’t kill myself during the two week med-free period, and then found out dipyridamole still didn’t work, that would do the job 😱😂

[SueJohnson in reply to 707twitcher]

My laugh for the day "that would do the job"

[Goagal in reply to 707twitcher]

My first laugh of the day - thanks

[Hidden]

Restless legs is also a symptom of opioid withdrawal, so your heightened RLS may well have been that. It's probably not possible to accurately judge the effectiveness of any medication until you're through withdrawal. I found dipyridamole worked well but couldn't stand tge headaches.

[Munroist]

Thanks for your thoughtful post. I think it's very useful to see other peoples experiences especially when you add your insights. Regarding how bad your baseline RLS is, I think Amrob's comment is very relevant, suddenly stopping a medication, especially an opioid, may lead to unpredictable issues of its own including withdrawal so it would be hard to know unless you allowed time for the effects of change to settle. Clearly that's not something you are keen to experience.

However people can be very adaptable, I have just spent a week with very poor sleep, on several nights waking repeatedly 7 or 8 times with just 30 minutes of sleep in between them and surprisingly I have learned to cope with it. I'm lucky in that I don't have to work so I can get a good hour or two in the morning to catch up and I am very averse to drugs and the side effects so it's something that just about works for me. I also know that if I manage a few things better such as food, weight, exercise and sleep discipline I can have much calmer nights when I'm only up 2 or 3 times.

[WideBody]

I augmented on DA drugs. Thankfully I augmented in about 1 years time. Dipyridamole works for me. I use it on an as needed basis. The headaches don't normally affect me, but I have been known to take Ibuprofen with Dipyridamole for a 1/2 punch.

I can go a month without Dipyridamole. Then back on it for a few days.

youtube.com/watch?v=XuIRPVN...(Not working as expected?)

Watch this Video from Diego Garcia-Borreguero, MD, PhD, Sleep Research Institute, Madrid, Spain, discusses the rational for using dipyridamole in treating patients with restless leg syndrome (RLS). One of the main issues in treating RLS has been the limitations of dopamine agonist use; they are effective in the short term, yet lead to dopaminergic augmentation and thus, an iatrogenic worsening of RLS symptoms over prolonged administration. Dr Garcia-Borreguero further discusses the role of hyperactive corticostriatal pathways and adenosine in the pathophysiology of RLS – describing the rational for developing drugs like dipyridamole which increase adenosine-based inhibition of these pathways. Results demonstrated that administration of dipyridamole has led to an improvement in the severity of symptoms for first-time treatment in patients with RLS; those who have been pretreated with dopaminergic substances tend to develop resistance, becoming unresponsive to medications like dipyridamole.

Good luck finding relief.

[amrob123 in reply to WideBody]

Thanks for the video link WideBody. If ever there was reason to not commence dopamine agonists, Dr Garcia-Borreguero couldn't make it clearer!

Similar to you, i took a DA at two separate points in time, the first for a year or so whereby I augmented. The second time, i tried it at a low dose out of desperation but again augmentation symptoms came back quickly, so i was only on it for a couple of months. Given that pregabalin works for me, as dipyridamole seemed to also in my brief experiment, it may be that the shorter the period of time on DAs, the better the chance of success on other medications. Or it may be that there actually are some differences between RLS and PLMD patients in the way they respond to the various medications.

[707twitcher in reply to amrob123]

Amrob123: I really wonder if there is a difference? I was only ever a PLMD sufferer until my last month on DAs. Then the daytime symptoms started with augmentation and they show up now when I miss or underdose my buprenorphine.

[WideBody in reply to 707twitcher]

The only reason I went to the doctor was the involuntary PLMD. I was living with RLS until then. I even googled “why do I rub my feet together to get to sleep”

[707twitcher]

Thanks to all for the comments. I didn't think the horrible RLS could have been a reaction to stopping the buprenorphine only 36 hours prior, especially with it being a fairly low dose and only being on it for 4 months. But maybe it was. Maybe the fact that I had been using the patch, with constant release of the medication, made withdrawal more likely. In any event, I know better than to ever stop using it cold turkey again. Heaven help me if I ever have trouble getting an Rx filled - it's a recurring monthly approval process given US FDA regulations surrounding opioids. And the video is a big help - I might have considered trying a slow taper off buprenorphine in order to try dipyridimole again. But my 12 years on pramipexole makes it unlikely that it would help. I wonder what research will show, assuming it's ever done, about people's ability to recover from the damaging effects of DAs years down the line....

[Shumbah]

I did 9 months solid like that, I could only eat 2 teaspoons of food a day one late morning and one at dinner time. I was on my way to switzerland for assisted dying when the dear Dr brooks emailed me and here we all are today Can you imagine how many more of us would have chosen that path by now if it was not for him responding to a little Aussie girl he did not know.

This disease is a killer . Sadly I frequently receive those messages .

If you take the miralax or something that draws water into the bowel and drink your 8 cups of water or hot tea per day.

The secret to taking less bup is to take you first tiny bit of bup before the RLS starts kicking in. I still break mine up nightly and tailor my dose to my daily needs.

[violetta254]

I too had horrible headaches with dipyridamole and my neurologist told me that is the reason he doesn’t prescribe it any more for its primary purpose. I got terrible RLS also but without reducing my methadone. I tried it for three nights and each day was bad with increasing headache also. I had augmented in DAs a couple years ago before stopping.