Gabapentin and methadone.

[dickJones]

I'm currently on 1100 mg of Gabapentin, to no effect at all. I've used Gaba twice before, backing out each time it stopped working so there's probably embedded resistance now. I'm minded to try Methadone at a low dosage. Should I back out of the Gaba completely first or could I begin the Methadone alongside my current Gaba dosage?

[Elffindoe]

Hi. Please clarify, what do you mean by Gaba?

GABA is a neurotransmitter, the opposite of glutamate.

Some people take GABA as a food supplement.

I'm also not sure what you mean by "embedded resistance".

However it does sound as if the gabapentin isn't working for you, so the next logical step would seem to be an opioid.

I'm no expert on opioids for RLS, there's a few options depending on who you can get to prescribe one and I guess what their preference is.

Oxycodone, hydrocodone, methadone and buprenorohine are all mentioned.

I hope you get sorted.

[dickJones in reply to Elffindoe]

Thanks, Effindoe. Gaba - abbreviation for Gabapentin. Embedded resistance - lack of effectiveness due to previous usage discontinued. Apologies for the confusion. I've requested a prescription for Methadone from my surgery and await ratification from the sleep clinic consultant. Would I have to withdraw from the Gabapentin completely before starting an opiate or could I begin dosage as I detitrate the Gabapentin?

[Joolsg in reply to dickJones]

I'm on Buprenorphine and added pregabalin for a short while to counter panic attacks on opioids.Many people take both meds so I think you can start the methadone and slowly reduce the gabapentin but the doctor prescribing the meds will reassure you on that.

Gabapentin should be reduced slowly to minimise withdrawal symptoms.

[dickJones in reply to Joolsg]

Thanks for the info, Joolsg and yes to gradual withdrawal!

[Jimbo77 in reply to Joolsg]

I was on both for quite some time. I believe you can take both as a combination therapy indefinitely if need be.

[dickJones in reply to Jimbo77]

Thanks, Jimbo.

[Elffindoe in reply to dickJones]

No problem, thanks for clarifying.

I am easily confused, but be aware that GABA - all upper case does exist and is a different, but closely related substance.

Confusing one with the other could cause problems.

Diminishing effectiveness is either "failing" or "tolerance", rather than resistance.

Unfortunately, in the medical world, apparently normal everyday words are used in a different way so it's sometimes necessary to know exactly what we mean to avoid misunderstandings.

Yes you can start taking the opiate before stopping gabapentin. They are sometimes deliberately used together as a combination therapy. In that case doses of both can be kept lower.

I hope you get the ratification and all goes well.

Best wishes

[dickJones in reply to Elffindoe]

I'm aware of GABA, the neurotransmitter and its role in the malfunctions that underpin our conditions. But as a pedantic ex-English teacher I assumed that the lower case form 'Gaba', as an abbreviation for Gabapentin would be contextually self-evident. But you're right, it's confusing and I thank you for the correction.

My doctor used the term 'tolerance' to describe my easy assimilation of both Gabapentin and Pregabalin in single evening doses rather than staggered amounts during the day. But I guess even the practitioners sometimes confuse lay and medical vocabulary!

Fingers crossed for the inclusion of opiates at this point in my long journey through all the various options. When RLS and PLMD are at their worst they are unendurable. I wish all of us medicinal relief and hope for more serious, focussed research towards more substantive treatment.

[Elffindoe in reply to dickJones]

Hiya, I'm afraid standard English is not the same as Medical English. Many words used in every day English, have different meanings in Medical English.

"Augment" is a good example.

Particularly drug names that can be unintuitive and long can be very similar, but different, as applied to different drugs. You need to make sure you give the right drug!

Incidentally, "Augmentin" is a drug name!

To further confuse, where one drug e.g acetominophen (Paracetamol) is given at the same time as another drug e.g. codeine, the added drug can make the original drug more effective. This is called "Augmentation".

"Tolerance" is a technical term applied when after repeated doses increasing amounts of the same drug are needed to achieve the same effect.

This is signifcant because drugs which cause tolerance can be addictive.

This is quite a widely accepted meaning so I'm not sure where your Drs coming from.

msdmanuals.com/en-gb/home/d...

Drawing a line under that however, there is quite a lot of evidence for the effectiveness of opioids for RLS.

They're not ideal, but I think you'll find one effective and yes, lets hope more research comes out for better drugs, or non drug remedies.

Areas of promise are dipyridamole, soon, I believe to be clinically trialled.

Perampanel, a long way off yet.

repetitive Transcranial Magnetic Stimulation r-TMS

[TheDoDahMan]

Hi, dickJones,

I finally got a prescription for low-dose (5 mg, twice daily) methadone and consider it to have saved my life. But I live in the USA and have heard that UK residents are denied methadone for RLS, in favor of other opiates, usually with poorer track records for our particular needs.

Have you heard differently? Best of luck in obtaining it.

[Joolsg]

Dick, if you do get Methadone, let us know as you'll be the first person in the UK I know of to be prescribed it. Most GPs and Neurologists are, for some strange reason, resistant to Methadone ( and until recently Buprenorphine) for RLS, despite it being the most common opioid used for severe, refractory RLS in the USA.More and more people are now getting Buprenorphine and it would be interesting to see if the same can happen with Methadone.

[SueJohnson]

You may need more than 1100 mg of gabapentin. I take 1500 mg and get complete relief. Are you taking more than 600 mg in one dose?

[Hidden]

For what it's worth, Methadone would be my first choice for recalcitrant RLS, which in a lot of cases is due to the use of DAs. Followed by Buprenorphine and then the Neupro Patch. Pregabalin would be dead last with Gabapentin close to last. But that's me and what my research tells me. The three drugs I mention are the only ones that down-regulate our excitatory D1 receptors as well as sadly our D2 receptors. As far as I'm concerned, if you're going to take something that "agonizes" our D2/D3 receptors (even if it's to a much lesser extent than the DAs) it has to simultaneously down-regulate the D1 receptors. It's when a drug isn't an equal time agonizer that we get into big trouble, meaning " fairly quick tolerance" "augmentation" and hellish symptoms upon withdrawal. The strangest article I read on this subject was the "dosing" of methadone and buprenorphine. Now mind you these studies were conducted on mice, but they reported that it's only by "binging" methadone, meaning taking the full dose once a day that it will down-regulate the D1 receptors otherwise it will up-regulate them no different than other opiates and pregabalin. With Buprenorphine they found that it must be taken three times a day in order for the drug to effectively down-regulate the D1 receptors otherwise it too will up-regulate them. Sadly, there doesn't seem to be any way to prevent them from down-regulating our already lousy D2 receptors. That's why I've been researching non-prescription drug ways to up-regulate our D2 receptors. I hate to say this, but with RLS you can never just sit back and enjoy the relief. You have to consider yourself an athlete and your receptors are your muscles and you need to "pump them up." And just like athletes keep pushing for the gold, we have to as well.

[dickJones in reply to Hidden]

Thank you for your response to my post. I have taken Gabapentin twice during the long PLMD voyage so far, both times to good effect over a decent period of time. I've just backed out of Pregabalin at 450 mg after a satisfactory year and a bit. That was then; this is now. Two separate sleep clinic consultants have told me that current recommended practice is low dosage opiates over all else so I'm seeking consultant ratification for Methadone at 10 mg via my surgery. So hopefully now those D1 receptors will get the seeing to they deserve, even if the D2s suffer some collateral!

[Hidden in reply to dickJones]

How was withdrawal from Pregabalin?

[BAK524 in reply to Hidden]

Lone Pine I know you've posted before your perspective on gabapentin/pregabalin, but can you explain again, what you would rate them last? After 4 weeks on pregabalin 150mg with satisfactory results, i experienced breakthrough RLS symptoms. So the following night I decided to up the dosage to 225 mg. (capsules are 75 mg, and the recommendations are to keep increasing the dose until it becomes effective, up to 300mg). That night I had horrible RLS. The following day I felt horrible from the lack of sleep and side effects. I was extremely low energy, sleepy, dizzy, in a fog all day. What concerns me is that increasing the dose from 150mg to 225mg actually seemed to trigger worse RLS. Do you think this is possible? I'm wondering if others have had this experience. I am losing faith in this drug and am considering opiate alternatives.

[Hidden in reply to BAK524]

Hi Fatniss, you couldn't have asked about Pregabalin at a better time, at least to preserve my sanity, not so much yours. Are you ready? I think Pregabalin is one of those rare drugs that is effective for treatment of certain conditions at a low dose, while at higher doses has just the opposite effect. I didn't read this anywhere, I am simply surmising.

Most articles indicate that pregabalin (in prescribed doses of 75mg to 300mg) works in relieving pain, and RLS, by reducing the neurotransmission of glutamate, which is an excitatory signal and is generally thought of as being over-expressed in pain conditions, and RLS. Pregabalin actually reduces some other excitatory signals as well. However, even the scientists aren't sure how pregabalin accomplishes all this.

From yet other articles I have read that our evil D1 receptors give off signals that increase or "potentiate" the neurotransmission of glutamate. So by blocking or ANTAGONIZING the D1 receptors we can stop this signal and hence some of that excitatory glutamate. If this is how pregabalin works then it's great for RLS in the short run, but bad in the long run because ANTAGONIZING the D1s only make them bigger and stronger and more EVIL in terms of RLS. Or it might somehow get the D2 receptors (by agonizing them) to release the calming dopamine signal which will also decrease the transmission of glutamate and also leads to a decrease of symptoms of RLS...in the short run, but in the long run will shrink our already shrunken D2 receptors. I'm going to assume that one, or the other, or some combination of the two, is how pregabalin works, because pregabalin has been known to lead to augmentation. 300mg of pregabalin leads to augmentation 50% less than .25 of prami, but it still leads to augmentation so it must affect our D1 and/or D2 receptors.

Ok, so everything sounds usual and normal as far as the drug world goes, right? The problem is I think pregabalin is more like a movie thriller and like any good movie thriller there has to be a twist.

The twist is that the scientific community now considers pregabalin a potential "drug of abuse" and for reasons just the opposite of the above. They believe, based on rat trials, that the addictive nature of pregabalin might be due to the AGONIZING of the D1s or the blocking of the D2s which lead to that kicky, heady, euphoric feeling you get with drugs like cocaine that keep that dopamine in your brain rather than allowing it to be taken up by the receptors. This is just terrible for the symptoms of RLS in the short run, but who knows, maybe in the long run is good for our receptors??? Anyways, the IMPORTANT point is that the clinical trials show none of this drug seeking behavior when rats are administered only 30mg of pregabalin, but at 60mg or 90mg, pregabalin did induce drug seeking behavior. Sometimes less is more. nature.com/articles/s41598-...

So what is the human equivalent of 60mg or 90mg? I'm gonna guess 60mg in rats translates to something greater than 300mg in humans. But who knows, maybe drug seeking behavior can begin at 40 or 45mg in rats (that they didn't even test) which would translate to 200 or 225mg for humans. And what this means is that it's possible when you took a dose of 225 mg of pregabalin it went from decreasing the excitatory glutamate signal at only 150mg to instead increasing it like in the rats. So yes, absolutely, you might have hit that conversion threshold when you upped your dose and instead of relief you got agony. MOREOVER, my theory explains why Derry gets RLS shortly after taking 300mg of Pregabalin. healthunlocked.com/rlsuk/po...

Remember, this is all me trying to put puzzle pieces together and I have no idea if I'm doing it correctly. No matter what, even before you raised the dose, it sounds like the pregabalin was losing its effectiveness for you. Rest assured, you did no permanent damage and may even have given your puny d2 receptors a little facelift :). People tend to demonize drugs, including me...hey I'm only human. However, I read that pregabalin can help our bodies repair the ever important myelin sheath after an injury. How frickin amazing is that? I've never heard of any drug that can do that. Doesn't mean it doesn't exist...I just never heard of it :).

To answer your question, I don't like Pregabalin (and possibly Gabapentin)because it does have a tendency to cause augmentation whereas as far as I can tell Methadone and Buprenorphine do not have this tendency. I think the reason is because even though both of these drugs down-regulate our D2 receptors they similarly down-regulate the D1 receptors and they may even do it somewhat equally. Neupro is in third place because it too down-regulates our D1 receptors, but I believe it down-regulates the D2 receptors to a much greater extent than the D1s, thus leading to the possibility of augmentation, but at low doses, it does this no where near as often or to the extent of low doses of prami and ropinirole and withdrawal is not hellish. Neupro is really a distant third to Methadone and Bup. Low dose Neupro (1 to 2 mg) might be good to use if a drug holiday from methadone or buprenorphine is called for.

So yes, please consider switching to an opiate as two sleep doctors told DickJones to do.

[BAK524 in reply to Hidden]

Lone Pine it seems that you've done a lot of research on this. I find your ideas intriguing, and quite frankly a little scary. I think you may be on to something. When you say pregabalin causes augmentation, I think you mean that it simply becomes less effective, and that a greater dose is required to be efficacious, and then at some point one reaches the maximum safe dose and has to withdrawal. Very similar - but not identical- to the dopamine agonists. If what you're saying is correct, then gabbapentinoids are basically a poor choice as a "first line" offense for RLS, as recommended by many. Part of me thinks we are all eventually heading towards opiates. Maybe we should just start there? I scheduled an appointment with Dr. Buchfuhrer in Southern California, but I can't get in until January26th. (BTW - His website does mention this about gabapentin: "The effectiveness of this drug often diminishes after 1-2 years". Isn't that great!) Meanwhile my RLS is going bonkers, and I can't sleep. I have trazodone, but it gives me bad heartburn. I emailed my GP for a prescription for a DA. I know she'll never let me try any opioids. I'm thinking the DA may buy me a few weeks of calm, and I'll stay on the lowest dose, but it does me make me nervous to try.

[Memmy]

Hi Lone Pine, I'm on 300mg prebagalin and although it stops my rls in the day, the night is another scenario. It's now 5,.30 am and I've taken my dose of prebagalin, a teaspoonful of Kratom and my legs haven't slept. Oh yes I took 2 advil too . Have you found any over the counter meds that work. I live in Greece and theres no way they will prescribe opiates. I'm getting hardly any sleep. I'm so tired but my legs aren't. I'm even considering going back to mirapexin which I know is a big no-no but while it worked it was excellent. I've been off it for about 6 weeks now. What do you think?

[Hidden in reply to Memmy]

Yes, you need to sleep. I believe our receptors return to baseline much quicker if you're well-rested. Nap if you have to. I'm not sure if you're at the end of your rope, but if it was me and I was at the end of my rope I would go on 2mg of Neupro (never never mirapexin) then refuse to leave my doctor's office or the ER until I got a prescription for Methadone or Buprenorphine...preferrably Methadone. Let the police drag me out of the ER room kicking and screaming. Not a good look for the hospital or the doctors. Once you're getting some much needed rest it's time to go to work. Try not eating after 7pm and until 8am. Add in vigorous exercise. Take a look at my profile page and try what I do for my RLS. Be aware that it's always good to take iron, but it seems to have less of an immediate effect, in the short run, if you're withdrawing from a DA. Still, take the iron and get your ferritin up, even if it doesn't provide immediate relief. We're all in this for the long haul.

Edit: Neupro for RLS gets an 8.0 drugs.com/comments/rotigoti...

Prami gets a 6.9 drugs.com/comments/pramipex....

Pregabalin gets a 6.3 drugs.com/comments/pregabal....

Gabapentin gets 7.4 drugs.com/comments/gabapent...

Methadone (from a ridiculously small sample size) gets the equivalent of an 8.0 ehealthme.com/cd/restless-l...

[Memmy in reply to Hidden]

Thanks Great advice

[Hidden in reply to Memmy]

Also, one night I would try lowering the pregabalin to below 200mg and see if that works out better. If all of a sudden your legs go crazy at this lower dose or you feel terrible you can immediately take the other 100mg. Nothing ventured nothing gain.

[Memmy in reply to Hidden]

I'm trying it tonight. Thanks

[dickJones in reply to Memmy]

Good luck. Do report back, Memmy!

[Memmy in reply to dickJones]

Nothing happened when I reduced the pregabalin by 100. I took 2 tramadol and 1/2 an ambien and slept well all night. I really needed a good sleep. Tonight I shall take 1 tramadol and 1/2 an ambien. Let's see what happens. Sleeping well is just so important. It's nearly 6weeks since I stopped mirapexin. It worked well for many many years but I had to come off them as I was augmenting