Restless Legs Syndrome (RLS) Discussion Board

I have a question. I recently stopped taking 0.5mg Pramipexole and started taking codeine. I take 60mg an hour before bedtime, and 30mg when I wake up in the middle of the night. The effectiveness of the codeine appears to be diminishing, but I might be premature in that belief. According to the Updated Algorithm from the Mayo Clinic: "When opioids are used appropriately for RLS, escalation of dose is uncommon, and misuse is infrequent". Yet there are a couple of posters that state they had to double and triple their doses within a few months. After that, one claimed their dosage remained constant for many years. Is that really tolerance? To me, it doesn't seem like tolerance; it seems like too low an initial dose. I don't think tolerance includes situations where the dose initially has to be rapidly raised, and then remains constant for years. The Mayo Clinic recommends that treatment should start at a low dose, and be increased as required. So which one is it? Are these people experiencing tolerance, or is their starting dose simply too low? The thought that I might be developing tolerance to codeine after just one month is rather frightening, as I view it as my last line of defense. If most RLS patients do not develop tolerance to opioids, I'd prefer to belong to that group, and not be an outlier who quickly develops tolerance. I should note that I originally took 60mg for my second dose and switched to 30mg for the last week or so. For a while, I thought I was doing just as well on the reduced dosage, but plan to go back to 60 mg tonight. In addition; should I keep my dosage as constant as possible? Is it unwise to experiment by altering dosage in search of an optimum level?

Thank you,

Don, there are no simple answers to your question. Are there individuals who develop tolerance to opioids, yes. One of the moderators of this board is one of them. However, as the Mayo publication states, they are in the minority. To get an idea, read through this report of results from the RLS Opioid Registry project. The project is being conducted to provide hard data for regulators to answer questions like yours.
https://www.neurology.org/doi/abs/10.12 ... 0000206855

As you will see, when you exclude individuals who needed to increase their dose due to other conditions, such as cancer and chronic pain, the number of increases over several years was minimal and the dose increases were more like adjustments.

As for adjusting your dose, at your point at the beginning of opioid therapy you need to work with your doctor to tailor your dose to your needs. It will probably take quite a bit of trial and error with most of the adjustments being driven by you since you are the one who knows how well or poorly each dose is working.

Also, remember that there are things that can impact how well your therapy is working other than simply the dose you last took. I had an intestinal virus this last week. There are opioid receptors in the gut and when I had RLS issues several nights this past week, I realized that the GI bug was stealing enough of my methadone to prevent it from controlling my RLS. I would have loved to temporarily increase my dose, as you have, but I am currently at war with my pharmacy benefit manager over my methadone prescription and didn't want to use any of the precious few pills that I have left.

Thanks for the paper Steve. The data gives me a better feel for the probabilities. The probability that I am currently developing tolerance is quite small. I need that to be the case. My prescription is for 30mg tablets; two at bedtime and two as required, for a maximum of four tablets per day. That gives me some leeway to experiment, but my doctor will not increase my dosage.

Regards,

Hi Don,

If your issues are mostly at night, I would recommend discussing with your doctor about incorporating an extended-release, ER, form of an opioid into your regimen. I don't know if codeine has an ER but several opioids do. Though the ER forms tend to be more expensive, I pay $39 for my ER vs $2 for my regular opioid.

Lissa

Lissa496 wrote: Thu Feb 27, 2025 4:57 pm Hi Don,

If your issues are mostly at night, I would recommend discussing with your doctor about incorporating an extended-release, ER, form of an opioid into your regimen.

Lissa

Hi Lissa,

I have an appointment with my doctor on Mar 6. Since I discontinued Pramipexole, my symptoms only occur at night. There is (or at least there was) an ER form of codeine. It's called codeine contin. It's made by Perdue Pharma, the maker of Oxycodone. My doctor will not prescribe Oxycodone, so he may also have an issue with codeine contin. Apparently codeine contin is taken every 12 hours. So the half life is probably about 9 hours, which is 3 times that of codeine. Codeine contin requires a new written prescription for each refill, so that would be a pain, but still doable. I plan to ask my doctor for an ER opioid prescription. Right now, I'm basically experimenting with codeine, but long term I need an ER opioid. Unfortunately, my doctor does not support the use of opioids for the treatment of RLS, although he has prescribed me codeine. If he doesn't support me at the appointment, I will switch to another doctor who I recently met. Like my current doctor, he knows very little about the treatment of refractory RLS, but he is willing to learn while my current doctor is not (he's somewhat arrogant).

Hi Don

You should not view codeine as your last line of defense, because it is a low-potency opioid and there are long-lasting as well as more potent opioids that are typically more effective in managing WED/RLS.

The disease is not constant so I find that a constant dosage is not appropriate. Doctors tend to expect us to take the same amount every day, but we can keep our total dosage lower by allowing the nightly dosage to vary (as long as the prescription is for the higher amount and not the lowest amount we might need).

Whether what you've experienced technically might be called tolerance, I don't think it's important. It is simply an initial dose that's too low. I hope your physician with all his arrogance can still recognize a man in distress and will do good by you.

Thanks Beth. I'll keep working with my doctor, although for most of us, it seems like we are the doctor. I want to get by on as low a dose as possible. My current dose now seems to be OK, but that will become clearer with time. I'm prepared to sacrifice some sleep for a lower dose. I say that not just on general principle, but because I'm not sure I like codeine (or opioids in general). I started on Gabapentin in 2011, went to a benzo about 2 years later, and then Pramipexole in 2014. I had no side effects with any of these drugs, other than augmentation with Pramipexole. Codeine has side effects, and I'm still trying to deal with them. I find it frustrating to take a drug for a condition, and then have to take something for the drug itself. It almost makes me long for Pramipexole. My doctor does not like opioids, and mentioned Gabapentin, Pregabalin and Gabapentin Enacarbil. I know the last two are preferable. I'm sure he will gladly prescribe them. My appointment is for March 6. At this point, I'm not sure which drug I'm going to choose. I gave up on Gabapentin a decade ago because I had to keep increasing the dosage, but I know realize my dosage may still have been too low. I may want to give one of the alpha 2 delta ligands a try. That doesn't appear in the Mayo Clinic RLS Management Algorithm, but I may still want to try it.

I was sure I'd read in one of your posts that you're taking something besides codeine, but I can't find it sorry
I think it's a good idea to take multiple meds, in order to keep the dose of each as low as possible. Gabapentin encarbil would be best to try, but it's expensive. I take pregabalin, that's good too. Gabapentin is absorbed erratically and is more likely to cause mood swings because of that (all of them can potentially cause mood swings and suicidal ideation). Any one of the three should help your sleep. They have the effect of lessening the WED/RLS symptoms plus helping reduce insomnia. They are in the 2021 Mayo paper; they're also in the 2025 AASM paper (in my signature link).

Keeping the dose as low as possible is good, not just to reduce the side effects you're having. There's lots of anecdotal evidence that taking enuf meds to completely eliminate symptoms makes the symptoms get a little worse (but that might apply only to DAs). Keeping the dose low makes it easier to get a new doctor to prescribe it. It also lowers the chance of developing an addiction, but that seems to be very unlikely with most of us.

I don't know if you have this, maybe you do, I have a sense of horror that I have to take medications. Not real horror, but a sort of background horror that I only notice if I think about it. It doesn't seem real, even tho it's been 17 years! And worse, a horror that I have to take an opioid, which makes it hard to travel and do anything. But I'll be darned if I'm going to let that stop me. I still manage to travel, even tho I have to see my GP every 3 or 4 months and have to get special permission to get more than a month's supply when I travel.

Thanks Beth. I'm visiting my doctor today. I'm going to ask for ask for Pregabalin and an extended release codeine. I absolutely have that horror! The horror is restricted to drugs acting on the central nervous system. Pramipexole is such a drug, but I never really thought about it that way. It was just a drug that fixed my RLS. I was quite ignorant about the subject. My anxiety has lifted, and I'm doing much better. I just used the coping techniques I learned decades ago. They worked much better than I ever dreamed possible. On a couple of days, I had debilitating anxiety. I was shaking inside and could barely function. Now the anxiety is low level, but I definitely need to keep working on it. My meds are working well again. Even if my doctor doesn't give me the Pregabalin, I will be fine.

This is sounding very positive I'm glad. I made a long post in the other thread.