Trialling Buprenorphine and Dipyramidole - experience

[Typicallygaslit]

Hello everyone!

I’ve been around for a little while but I’ve been waiting for something definite to report. At age 56, the RLS was getting very disruptive so I had to find an alternative to my usual sleep medication. It took me a few years. In the end I returned to my old GP, who listened and thought my suggestion about Buprenorphine sounded sensible. He was a first! I had tried everything else, but tolerated nothing. I have hEDS as well and things are clearly neurologically complicated. I really fear for the future (because of not tolerating most drugs, supplements and herbs).

I’ve been using about 500 mcg Buprenorphine sublingual for almost three months. The main drawback is moodiness and difficulty eating because of nausea. I’m quite worried about becoming depressed on this medication. Day time fatigue is also a problem especially if I haven’t slept enough - I experience sleep debt, which is new to me, but it puts me at risk of not being able to drive. I wonder whether maybe taking a really small does e.g. 5-100 mcg when I wake up in the middle of the sleep in the morning could ward off the low mood if it’s due to coming down from the opioid, but I still have to experiment. It does make me sleepy, but it’s not usually enough to get me to sleep. I seem to have to continue to take some other sleep medications, albeit lower doses than previously. I now take 12.5 mg quetiapine and some Zopiclone and/or Diazepam.

Please note!! I’ve TRIED to leave the quetiapine out since it exacerbates RLS but I just CANNOT sleep without it either. Presumably it calms down some of the hyperexcitability (catecholeminic activity) that causes some of my insomnia. My insomnia is very severe and I can’t handle any sleep deprivation. My schedule is still crazy, 5am - 3pm, that sort of thing, and it makes life quite unbearable.

I was also able to test Dipyramidole as my GP didn’t have any problem with it. Unfortunately I didn’t last long because of severe nausea and runny diarrhoea. So that was that.

My iron was 52 in June and I got it up to 74 after three months’ supplementation with ferrous fumarate (I don’t tolerate bisglycinate because of the glycine in it). I tolerated it ok for a while but now I feel that the iron is exacerbating the RLS. Anyone else find this?

I wonder if it has something to do with the idea that iron is poorly absorbed once you’ve reached the 70 mark. I’m not quite sure what to do, maybe try and keep it up by taking a tiny amount every once in a while. There are also other vitamins I don’t tolerate, notably B6 and that’s presumably because of its action on serotonin. I haven’t figured out yet whether B12 is also causing problems but I think it is. I also have problems tolerating magnesium.

All this hypersensitivity to serotonin boosting agents is very worrying as it really narrows down my options. I think it’s due to being a poor metaboliser of serotonin, but there could be other reasons. What I do know now is that I have the gene variant BTBD9 for poor iron metabolisation, and with it, also poor adenosine build up and low dopamine.

I finally got to see a neurologist after over a years’ wait, but it was a pointless visit. He completely ignored what I said in regards to restless legs syndrome and being unusually sensitive to serotonin. Instead he diagnosed me with functional neurological disorder which is just bogus. This year has involved really disheartening encounters with gaslighting health practitioners (on the NHS).

I can’t really see any other way forward right now than carrying on as I am now, ‘limping’ along rather than ‘walking’. I’m very tired of dealing with doctors, it’s been a busy year in this regard. So I hesitate to look for more help, especially as I don’t feel confident that they would help anymore than my GP already is. I did suggest Clonidine to him but he said no because it’s not licensed in the UK. So I’m out of ideas now. Any suggestions?

By the way, has anyone tried a beta blocker in order to lower serotonin and adrenaline activity, and did it cause insomnia and/or worsening RLS?

Lastly, can anyone suggest a safe antiemetic that doesn’t exacerbate RLS?

“[…] BTBD9 was observed to significantly reduce brain dopamine levels and led to an abnormal sleep pattern in mutant flies (182). The BTBD9 gene modulates transcription of ion conductance, cytoskeletal arrangement and protein ubiquitination and it enhances activity in rat striatum, a part of basal ganglia involved in voluntary movement in addition to largely comprising of dopaminergic neurons containing both D1 and D2 receptors (157). A study reported under expression of this gene causes hyperactivity and hyperexcitability in the calcium-gated dopaminergic neurons in striatum.” ncbi.nlm.nih.gov/pmc/articl...

[SueJohnson]

Since quetiapine makes your RLS worse I would stop it and ask for a prescription of Ativan or Xanax for your insomnia. Iron does not make RLS worse. Since you are at a ferritin level of 70, you could ask for an iron infusion, or you could take twice the amount every night at the same time, but no closer than 24 hours as that limits its absorption. Beta blockers worsen RLS in most people. Do you have high blood pressure since you suggested Clonidine which was rejected?

[Typicallygaslit in reply to SueJohnson]

Thanks but I thought I explained that I have tried to do without the quetiapine but it doesn’t work as I cannot sleep without it. It has many effects specifically on the catecholemines and I have not been able to find an alternative. I do take hypnotics as well but they don’t have the same actions. Iron infusion sounds mad given that small amounts of iron are already causing RLS at night. Iron does many things in the body so I suspect my system is overwhelmed by it and that it’s also action on SERT (serotonin transporters) as this could explain my sensitivity. I also would not get infusions in the UK. I hate to think how bad I could get from them anyways.

I suggested Clonidine because it is a sedative that also calms down adrenergic activity, which is a well known problem for people with hEDS even when we have low rather than high BP, however my GP was only able to suggest a conventional beta blocker and it didn’t really work for me as it made me excessively tired in the day time and wakeful at night. I don’t know if the wakefulness is due to the fact it lowers melatonin or because of aggravating RLS, it was impossible to tell. I only used tiny amounts. As it stands, the least difficult medications for the insomnia is low dose quetiapine which also has an anti-adrenergic action, and a non-benzo or benzo to complement. The Buprenorphine helps with the RLS so in effect it’s helping me tolerate the quetiapine. I have not discovered any other combo that would get me sleep.

[LotteM]

Difficult and complex situation. Although it seems your gp is trying hard to be helpful.

I just want to do a suggestion re the buprenorphine. You mention you take (up to) 500mcg a night. And you also mention moodiness that may be opioid/buprenorphine-induced. I had that. Moodiness, restlessness during the day that I could counteract temporarily by a daytime dose of buprenorphine. Upon suggestion by my pharmacist, my neurologist trialled a 7-day patch of buprenorphine. Because of the different absorption route, I get by with a far lower dose (5mcg/h) and it dealt with the mood swings and restlessness periods during the day when the buprenorphine dose wore off. I remained on the patch, have been for almost a year now. Worth a try for a short while (1-4 weeks?).

[Typicallygaslit in reply to LotteM]

Thanks LotteM, that’s interesting. Yes, it could be that there’s a low in the afternoon because of this. I seem to feel it less if I take a small dose in the morning but I haven’t tried it on all days so I’m still unsure. I’ve typically done it on days when I got by on 400 mcg at night and then woke up in the mroning and felt I could ‘afford’ another 50-100 in order to get back to sleep (the insomnia and RLS fluctuates a lot). I’ll bring up the idea with my GP if he still has patience with this. The only thing I worry about is that patches tend to get loose very quickly on me. I have an HRT patch that I sometimes have to change more often than I should because of sweating and showering. Thanks 👍

[Shumbah in reply to Typicallygaslit]

All patches should be coved with

micro pore tape this protects them and gives them better absorption due to no lifting .

[Typicallygaslit in reply to Shumbah]

Hm, well that’s an interesting thought. I have used tape sometimes when it’s been lifting but it feels pretty horrible on my skin. I’m very sensitive to touch. But I’ll think about it.

[Typicallygaslit in reply to LotteM]

By the way do you feel tired during the day? Is it less on the patch? For me it’s as though I have to consummate the sleep and if I don’t, I will feel a heavy sleep debt that makes it impossible for me to function (let alone drive). And I wonder how this would be if I was on a patch or spread the tablet over the course of the day.

[LotteM in reply to Typicallygaslit]

I feel much better since I switched to the patch. I still felt tired, but my sleep was broken and days interrupted owing to hot flushes. I was and still am on HRT, but for years I was on an ineffective old-fashioned one. Fairly recently I was given the 'standard' HRT again, my hot flushes have stopped and I feel much less tired!

From your story it appears to me that the bad sleep is feeding your tiredness. Even if that improves (I hope it does, soon!), ot may take a while to recover and feel less tired during the day. And as we are all different, discuss with your doctor for a trial and see how it goes. After many years of trying medicines that didn't work well, I learned you can tell when something does help. Good luck!

[Typicallygaslit in reply to LotteM]

Thanks LotteM. I’m chronically fatigued anyway but definitely more tired in the day (and especially in the late afternoon) on Buprenorphine than I was before when I only used sleep medication. The tiredness feeds into the increased ability to sleep so it’s difficult to imagine life without it. I will discuss this with a pain management nurse this week and then I’ll bring it up when I see my GP. I’m starting to think I really might feel better with a more constant supply in the system. Thanks! ☺️

[TeddiJ in reply to LotteM]

Hi! I wonder if the patch totally alleviates the worry about the teeth issue? Or, if it is due to dry mouth. I think you have addressed this before, but do you think it affects your teeth this way?

[LotteM in reply to TeddiJ]

Hi Teddy, I don't seem to experience the dry mouth and/or tooth decay side effect of buprenorphine. The risk seems higher with the sublingual tablets, but definitely not absent with the patch. I have been on bup for two years now, a long year on the tablets and a short one on the patch. So far so good. Dentist appointment this week, by the way.

[TeddiJ in reply to LotteM]

thanks, Lotte! Good luck at appt! Let us know-maybe they will have more insight.

[Pippins2]

Hi ,Zofran is a safe anti nausea med

[Typicallygaslit in reply to Pippins2]

Ondansetron, yes, I think I worry that it can induce serotonin syndrome, as I seem to have a propensity for serotonin intolerance.

[Joolsg]

I dealt with the Buprenorphine induced nausea with my medical cannabis oil. It has 20% THC. It stopped the vomiting & severe nausea & I only need to use it occasionally.I take 400mcg sublingually and experienced anxiety, panic attacks & depression.

I added 25mg pregabalin at night & it has totally resolved the anxiety etc.

Dr. Buchfuhrer ( A top US expert) recommended I try it when having Oxycontin panic attacks.

It acts as a sedative as well so you may find by adding 25-50mg pregabalin at night, you will avoid the depression and be able to sleep so you could slowly reduce the quetiapine.

And most of us have experienced medical gaslighting and total ignorance from UK doctors and neurologists.

They know zero. They might see 1 or 2 RLS patients a year so they have no idea how to treat RLS. They've never been taught it or how to treat it effectively.

There are around 10 US experts who see thousands of RLS patients every year so they know dopaminergic drugs are dangerous and low dose opioids effective.

[Typicallygaslit in reply to Joolsg]

Thanks Joolsg. I struggled with a couple of GP’s for a while, they wouldn’t listen. I then went back to someone I used to see back in the days about my insomnia and told him no one wanted to deal with my issues. Thankfully he at least listened and thought I made sense. I’m not sure about CBD oil, I’ve tried some pretty expensive stuff that had no effect and I have a suspicion that anything cannabis related wouldn’t work for me. But I could be wrong. Where do you get this potency oil?

I have tried 25-75 mg pregabalin in the past, didn’t really seem to suit me. At the time I thought quite badly of it but they were different times for me, for sure. I was also using things that were kicking off the insomnia. I tried gabapentin quite recently and was very sick. Most medications make me very sick with diarrhoea. I think it has to do with extreme sensitivity to serotonin but it’s hard to know as neurology is so complex. The low dose quetiapine has always been harmless except for the slight increase in RLS. I have tried to do without but it didn’t make a huge difference, only made me less likely to get to sleep and in need of copious amounts of hypnotics. My doctor is fairly content at the moment. I worry about pushing his patience with more trials hither and tither. But thank you, I appreciate your experience - I will have a think about this.

[Joolsg in reply to Typicallygaslit]

I get the proper cannabis from the Medical Cannabis Clinic. Cannabis was legalised in the UK for medical use in 2019. It's not on the NHS so you have to pay a private consultancy fee and the cost of the cannabis.

gabapentin also gave me diarrhoea but pregabalin didn't. You could try adding the smallest 25mg dose at night and see if it helps sleep & stops the anxiety/depression.

Quite a few report depression on buprenorphine which is frustrating because it really helps the RLS.

Keep your GP on side. He sounds wonderful. Perhaps print off your research & hand him copies for bedtime reading, explaining that RLS isn't taught at med school so he could quickly become a top expert and help thousands.

Hope you find the right combination of meds.

[Typicallygaslit in reply to Joolsg]

Yes, I’m aware of the cannabis situation but I can’t spend that sort of money. The couple of times I tried someone else’s spliff didn’t feel helpful to me but it’s hard to say. Ok so maybe then it’s worth me asking for 25 mg pregabalin to try, doc should be ok with that. Diarrhoea is definitely a big warning for me to not push a substance.

I’m not good at explaining things to doctors but I’m working on informing this one… or at least giving him some new ideas to think about. I did print out the documents but the other GP’s spat on them. I’m nervous about it all lol, especially don’t want to upset the one who agreed to work with me. I almost did last time I was in there, because I challenged conventional NHS belief systems. Gotta walk on egg shells…

[Joolsg in reply to Typicallygaslit]

Best of luck. I hear you.

[Typicallygaslit in reply to Joolsg]

Joolsg… did you meant to say the pregabalin has helped several people with the depressive mood from Buprenorphine? I’m feeling a bit desperate today as I popped 100 mcg Buprenorphine this morning and it made me feel emotionally worse. I’m just about to start crying for no reason. So I’m not sure spreading it out over the course of the day is such a good idea after all. I fell asleep from just 400 mcg (plus the other meds) so I’m still within the 500 mcg today, but it seems to be too much from the point of view of my low mood. This improved while I was on Dipyridamole but alas, I didn’t tolerate the effect on my digestion.

Just another thing. Do you use any hypnotics at all? I seem to still need some (but weirdly, my tolerance is poor for some benzos). Like you, I have spinal lesions and possible autoimmune activity so we may be responding in similar ways to the drugs and I’m therefore eager to hear your experience.

[Joolsg in reply to Typicallygaslit]

Yes, I noticed an immediate improvement in the anxiety and low mood and one or two others also find pregabalin at night has helped.You could trial it for a week.

I also split the Buprenorphine dose. I take 200mcg at 10pm.and 200mcg at midnight.

I take 25mg pregabalin when I wake for a loo break around 3am. That way I don't notice the drowsiness in the day that can happen with pregabalin.

I'm very sensitive to opioids and kratom and had anxiety/ panic/ depression with Oxycontin and Buprenorphine.

Fingers crossed a small dose of pregabalin reduces the depression without causing awful side effects.

[Typicallygaslit in reply to Joolsg]

Ok, thanks, yes I also seem very sensitive. I’m assuming you go to sleep just after midnight. At the moment, I’m typically not getting to sleep until 4-5 am so it’s making a right mess of things. I’ve tried breaking up the dose as well but so far haven’t had any clear response either way. I will certainly consider this path.

[Joolsg in reply to Typicallygaslit]

That was my sleep pattern on Oxycontin and pregabalin. RLS follows the dopamine cycle. Dopamine is highest from 6-7am and then reduces over the next 24 hours. So evenings and night time is when dopamine is at its lowest and when RLS is at its worst.I still haven't reverted to a normal cycle after decades of severe RLS. I fall asleep around 2am but am trying to get to bed earlier and find a 'normal' routine.

[Typicallygaslit in reply to Joolsg]

Yes, exactly, I finally figured out why I could never reset the schedule and why as I’m ageing, it just keeps on slipping further and further into the morning with the best sleep in the afternoon (this year it moved from 2-3 am to 5-6 am). This is a very worrying prospect as I’m getting older (as it must be for many of us with complex diseases). With Buprenorphine I’ve sometimes been able to sleep earlier but then I tend to sleep too many hours the following night which makes it harder the next night and so on and so on… a vicious circle that has made me open to soul destroying moralising abuse from doctors since it all started twenty five years ago. I felt so alone, no one else was like me. And of course they still won’t listen even when there’s finally evidence that this is a real disease.

As we’re moving into old age, it’s increasingly important that we find support from each other - I can only say thank god I’ve found people who are like me.

I will keep testing different ways of taking the meds. Unfortunately I often wake up in the late morning, unable to get back to sleep, and I sometimes overdo it with the medication so I sleep longer than I should.

[Pippins2 in reply to Joolsg]

Jools do you think medical cannabis combined with Pregablin would be enough to control (to some extent) severe RLS ,? Pipps x

[Joolsg in reply to Pippins2]

It really depends on the individual. A lot of people do really well on between 200-400mg pregabalin but it really did nothing for my RLS.Nor did Oxycontin.

Cannabis was better than both because it knocked me out for 4 hours between midnight and 4am. But I'd then be woken repeatedly with severe RLS.

I know SueJohnson completely controls her RLS with gabapentin alone.

It's still trial and error.

Mine is now completely controlled with Buprenorphine but I had to add 25mg pregabalin to stop the opioid induced anxiety/depression.

I'm now convinced that for many who've spent years on Dopamine Agonists, only opioids will fully control severe RLS.

Certainly Dr. Buchfuhrer mentions it and he uses methadone and Buprenorphine more and more.

[Pippins2 in reply to Joolsg]

Thanks Joel's Pregablin doesn't do much for me but was wondering just how effective the medical cannabis is as never tried it .Thankyou x

[Goldy700]

I can speak to cannabis for nausea and to help with sleep. The good thing about cannabis is it uses a different pathway to the opioid pathway and it might be worth you giving it a go. Cannabis has a very low addiction scale - (6 vs 100) so is fairly safe.

[AnotherRLScase in reply to Goldy700]

I find the specific type of cannabis makes a difference. It's legal where I am, and there are a couple of brands that really help me to sleep ("Sleepy Time" by Absolute Extracts and another sleep blend by Froot). Others I've tried don't help at all. I don't know what the magic blend is, just that some work and others do nothing.

[TeddiJ in reply to AnotherRLScase]

Hi. Are you saying it also stops your rls? With no other drugs? I would love to use cannabis only but instead I am mostly using kratom, which stops it almost immediately. So far, the indica cannabis gummies I have tried have never stopped the rls. Thanks!

[AnotherRLScase in reply to TeddiJ]

That would be wonderful if it did. It helps enough that it might be possible, but I never really had the opportunity to try the kind that really helps me before I started the dreaded ropinirole. I also take iron every other night. I can say with certainty that it helps me fall asleep, and I often get a full nights rest. Even if I do wake up, it's easily managed by one round of stretching.

[Hidden in reply to AnotherRLScase]

Why would you take the iron every other night if it helps you fall asleep (it does me as well) and keeps you asleep. Is it because someone on here, who doesn’t understand a thing about iron, told you to take it that way? I recommend taking it every night, keep the Ropinirole as low as possible and think about adding a counter weight to the DA. Meaning take a dopamine antagonist in the morning - be it the magnesium or berberine or whatever other natural substance you can find by googling natural dopamine antagonist.

Once you’re back on a dopamine antagonist for a while, and feeling good, try challenging yourself by lowering the Ropinirole by a hair. A few months later another hair. Play, have fun, have a sense of adventure with it as long as you’re feeling good…why not? Your experience will likely help others