In the next week or so I will be starting a series of ketamine infusions for treatment resistant depression 🤞.
While researching the therapy I came across several articles on how ketamine infusions and oral ketamine are being used and studied for RLS relief.
Theory behind it (which I would preface as one of many) is:
"Scientists believe that the main cause of Restless Leg Syndrome is an overactivity of the N-methyl-D-aspartate (NMDA) receptor in the brain. Ketamine works by attaching to the NMDA receptor and blocking it from being activated by glutamate, a neurotransmitter. Thus, ketamine aids in decreasing the overall activity of NMDA, which in turn reduces symptoms of Restless Leg Syndrome. "
I'll report back on my experience. But I may not get an accurate reading on whether it helps as I will still be taking my regular meds that work fairly well. I will ask questions about RLS and Ketamine and if any other patients treated have seen any benefits.
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ziggypiggy
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It's from information from a ketamine clinic. I didn't link it originally because they don't refer to any study when quoting said scientists.
The second link is an abstract case study. I couldn't get through to the actual study. Not sure if this is what the first quote was referring to. That's why I hedged the wording as one of "many possible theories".
I'll keep trying to dig a little deeper.
Several ketamine clinic websites mention it being helpful for RLS through the NMDA receptor. So there may be a foundational study somewhere. Or, it could merely be marketing to attract a larger patient base for this kind of therapy.
Here's another study on the glutamate RLS connection. You may be familiar with this one. They mention the ketamine case study towards the end. Gets a little scientific, but I think you enjoy getting into the gritty deteils😉.
Thanks again. The association of glutamate dysfunction with RLS is well accepted now and hence this is why the gabapentinoids are used to treat RLS.
Ketamine is another matter.
I have looked at the article on ketamine which is very brief and gives two "case studies". These do suggest that ketamine may be effective for RLS. However,this is only two people who had a history of spinal problems and one had been on antidperessants, so they are not typical, RLS sufferers.
This is not a good basis for treating RLS with ketamine.
That was 2002, Iwill look to see if further studie looked into this in more depth. It will be interesting to see what your experience is.
Yeah. I agree. I read somewhere that pharmaceutical companies aren't really interested in trying to get true ketamine products to market for depression because there is no money it. Spravato nasal spray for depression is based on esketamine which is just part of ketamine and they were able to push it through as a uniquely different drug and thus able to charge a fortune. And the clinic infusions are out if pocket and are administered by a licensed anesthesiologist.
The profit issues may be part of the reason research has been minimal for all uses of ketamine.
We know if it worked and there was money to be made, they would have been looking into it a lot closer.
Anytime I come across something RLS related I haven't seen before, it always gets me a little excited. Posting here is kind of like our own little peer review process. Thanks for the discourse as always.
The first link you give is to the home page of an organisation that offers treatments. It does, as you say, refer to scientists, but doesn't idnentify them. I'll try and find out who they are!
The second link is to an article originally published in Anestheisa and Analgesia journal in 2002.
This is, as you say a better link to the same article.
I've also found another two things one of which is a letter to the journal editor about the above article and another is a reply. Both dated 2003.
The letter includes the following
"RLS may be mediated by overactivity at the N-methyl-D-aspartate (NMDA) receptor. I wonder if they have, therefore, considered the use of magnesium as therapy for this condition.
Magnesium is a physiological NMDA antagonist and deficiency of magnesium may be causative factor in RLS "
The reply includes
"While we did not give our patients magnesium, we agree with Dr. Fawcett that more attention needs to be given to the modulation of NMDA receptor activity in the treatment of this common problem. "
I was give a series of lidocaine/ketamine infusions at a pain clinic, tho not for RLS, which I have, but for nerve pain deriving from RA, rather than diabetes. They were forced to discontinue it during the fourth session as my bp skyrocketed. While it felt good during treatment, the pain would return within an hour or so. Wish I’d known of the link to RLS at the time so I could have seen if there was any effect on it. Will be interested to hear the results.
I have read of one or two posters on other forums who have experienced relief from rls using ketamine (one - from memory - who was administered ketamine in the form of an enema! - it is possible I am mis-remembering this). I hope it works for you. It is wonderful when you get the 'two birds for one stone' relief.
I agree very much. I suffer from neuropathic pain caused, I understand, from small fibre neuropathy as well as RLS. I currently take a high dose of Pregabelin which can help with both. I have been receiving help from a pain consultant who has mentioned the possibility of having intravenous ketamine or lidocaine if the current drug regime is not working. As an aside I am interested in whether methadone might be effective for both pain and RLS control
Methadone would seem to fit the bill for pain control and rls treatment. As an added bonus I read recently that it is now believed that methadone affords additional protection from covid - there is a very low incidence of covid amongst the community of drug addicts receiving methadone treatment which was completely unexpected and is being attributed to methadone.
I wonder if this is a common issue with rls suffers. After over a decade of treatment for RLS and various unexplained pains my GP thinks I have small fiber nuropathy as well.
I have had two nerve conduction studies , three years apart, that both indicated small fibre neuropathy. I will probably be having a punch biopsy which will demonstrate whether I have SFN. All a bit academic as the only treatment is painkillers!
Yeah. I've heard mixed reviews. I'm trying to find a good balance of expectations. But, I've tried nearly everything else short of psychedelics or the Vagus nerve implant. But I'm 51 and still ticking, so if it doesn't work I'm no worse off. I hope.
Hi All, Ziggypiggy. I don't want to put a dampener on your invaluable research. RLS is a desperate thing to try to calm. Do you know what Ketamine is? Do you know what it does to the mind (no, I have no experience), but believe it or not the vets often use it for sedation, and I wouldn't put my cat through it again. She woke up terrified, not recognising us, very unwell.
I understand that Ketamine is used for sedation, but it has been used elsewhere.
It is easy to compare cannabis to the milder cannabis oil.
I have experience of what it does to the mind I was a raver and took an E that was actually ketamine it’s evil stuff. I’m not a druggie and I am older and wiser now. Trust me the mind blowing effects went on for several years. Please please stay away from it unless a GP is controlling the dosage. I very much doubt any GP would be prepared to prescribe it.
Thanks for your concern. The Ketamine clinics have been around for many years. The dose given is much less than what would be given to go under. A licensed anesthesiologist will be there to supversise me. And I will be released to a family member when effects subside. Of course risk/reward is weighed for any treatment. Patients are referred for these more off the wall treatments when all others have failed. My psychiatrist referred me and I went through the entire evaluation process.
Severe chronic depression is so dangerous in itself. Living year after year having suicidal ideations more days than not just wears you down. All relatively safe options are on the table as a means relief.
Thank you Ziggypiggy for your understanding. As you rightly read this is a concern. I also realise the desperation some go through for depression and can sympathise with you. Even then I have no idea as to your circumstances. I wish you well and cross-fingers
Please be careful with the Ketamine injections. One of my dearest friends of forty years and ex teenage sweetheart recently had a series of six of these infusions after nothing else helped with her depression. I’ve heard they are good for many individuals. For her it did not end well unfortunately. Good luck and hope it works for both.
Thanks, fingers crossed. I've weighed the risks. It doesn't work for everyone and isn't free of side effects. But I want to flip over every rock before I give up looking. It's used in conjunction with psycotherapy. The day after a treatment I attend therapy, supposedly with more openness to developing and leaning into "right brained"processes.
That’s great I really hope it works for you. From what I’ve heard it’s an ongoing process and quite a few infusions may be needed. It’s funny before my friend I only thought it was used for nerve pain! I know your in the States but for those in the UK who are finding it difficult to get this treatment on NHS, there is currently a research project at Oxford University offering it. Sorry don’t have any more info than that. My friend was desperate and paid for her sessions privately but unfortunately won’t be able to take her place at Oxford but they are doing it.
Advice on use of Ketamine: BE VERY CAREFUL. My wife recently had two major operations. Life-threatening stuff. As part of immediate operation recovery regime, she was give i.v. Ketamine in the Intensive Care Unit. It caused extensive, disturbing and traumatic hallucinations. Altered reality in a very dangerous way. Instead of preventing "post-op dementia" it actually caused it. Luckily, the dementia did not became permanent. She is still suffering flashbacks, has been diagnosed with post-traumatic stress disorder caused by the drug and has to have counselling to help her recover from it.It does not affect everyone in like this. But if it does hit you in this manner, you become utterly convinced that the hallucinations/altered reality are the real thing. Therefore, have someone with you when you start the Ketamine therapy to make sure you are OK. You might even wish to write a hand-written note confirming their role as, if you do react, you probably will not believe them when they tell you that you're hallucinating.
Thanks. Yes, it's less of a dose than is used to go under. It's actually intended to provide a slight hallucination for a short period. The theory being that it will open new pathways for developing heathy coping mechanisms as opposed the the distorted ones already hardwired in the brain. I've got a support system in place for the entire process. Thanks for your concern.
Hi, still looking. Despite the "Scientists believe". and "Studies have shown". I haven't yet found any scientists or studies since 2002.
Studies have shown however, that ketamine can "relieve the pain associated with RLS". NOT the RLS symptoms themselves.
There's quite a bit of info about ketamine as a date rape drug, which isn't helpful.
Rohypnol is generally referred to as the date rape drug. But many drugs can be used for that purpose. Good thing that's not my intent though huh?I will have no access to the medication and it will be administered under the care if a licensed anesthesiologist medical professional.
Many medications can be used for all sorts of applications.
Pain relief is a start I guess. Definitely a symptom of RLS for many. For other benefits it may have to come down to stories shared by individuals. If enough say it helps then further research may be warranted. That's often how a movement for off label treatments start out. Maybe in a few years we'll hear more and more stories shared which can help a person better decide for themselves. And may also lead to more current research.
Check out this witches brew treatment for RLS I came across on a pharmacy compounding website. It's got a very recent date. Not sure what to make of it. I couldn't find any other info on it or who might of written the scrip for them to compound.
I notice you rarely include pain as an RLS symptom. I've always come across it in the symptoms sections under RLS. Is there an alternative reason on why it shouldn't be included as a symptom? Just curious.
You're correct, I don't often mention pain as a symptom of RLS.
My reasons are firstly and mainly, because it isn't one of the validated RLS diagnostic criteria and that not everbody gets it. I don't experience it myself, never have.
Secondly, there are many causes of pain and I would never wish to dismiss pain as being part of somebody's RLS when in fact, it could well be something else needing investigation, e.g, neuropathy.
Although some people do experience pain due to RLS it is not a necessary symptom of RLS.
The urge to move IS a necessary symptom without which there is no diagnosis.
One further point is that many people seem to believe that if something works for pain, then it should work for RLS and in many cases, there's no evidence of this.
Examples
Some people claim paracetamol works for their RLS. Only a few. There is no reason why it should
Some people claim a TENS machine works for RLS. Only a few. There is no reason why it should
Opioids work for RLS, but it's not because they're "painkillers"
IN SUMMARY
I have read sources that list pain as a symptom of RLS, but I haven't come across many. The point is, it is not the only symptom, it may not necessarily be due to RLS and it is not listed in the diagnostic criteria.
Obviously when it's clear that somebody DOES have a RLS diagnosis and it's clear that their pain is NOT due to anything else, then the pain needs additional attention. This is recognised, certainly in the UK guidelines forthe management of RLS.
This study is interesting. If I am interpreting it correctly if implies that certain painconditions and RLS can occur based on the underlying cause. The same conditions that exist, whether it be low iron or dopamine disregulation, are the root cause for each symptom. I'll go back and reread it but let me know what you think.
Hi, if I'm right you are thinking that both pain AND RLS can occur due to the SAME "root" cause. I'm not sure how true this is,
If you're basing this on the article about Baclofen, Clonidine etc. I don't interpret it that way.
The way I interpret it is that each of the drugs counteracts a specific different symptom of RLS.
All current drugs for RLS do this, i.e. they are "symptomatic" treatments.
None of them treat the cause.
I find it difficult, from the literature to say what the "root" cause is. The treatment nearest to dealing with any "cause" of RLS is iron therapy.
There are however, other factors exacerbating RLS, i.e. make it worse.
These factors may have a diiferent cause.
Peripheral neuropathy is an example. If somebody has RLS and develops neuropathy, it can make RLS worse, but this doesn't mean the neuropathy "causes" RLS. Not everybody with neuropathy has RLS! Or does it mean that both have the same cause.
There's a lot of things that cause pain and pain is a symptom that can occur in many conditions.
Some painkillers then may be used for the symptomatic relief of pain associated with RLS e.g. ketamine, but this doesn't necessarily mean they treat other symptoms of RLS.
Opioids, sometimes referred to as "painkillers" are actually a different class of drugs and can treat RLS symptoms.
I can see that you'd really like it if ketamine did treat the root cause of RLS. If it turns out that it does, I'd think that's great too.
However, I'm not sure that it's side effects and risks make it a good treatment. The story of dopamine agonists is similar.
No this is the study I was going to have you take a look at. This the second time my links haven't appeared. But I'll try again. I assume human error. Thanks for putting so much time into your last response. I'm sure you were like "what the heck?"
"Musculoskeletal pain is associated with restless legs syndrome in young adults | BMC Musculoskeletal Disorders | Full Text" bmcmusculoskeletdisord.biom...
Sure enough it does suggest an association between musculoskeletal (MSK) pain and RLS.
In addition, although I've never read any actual studies, there is anecdotal evidence that childhood RLS is dismissed as growing pains.
Furthermore reflecting on my own experience, I have been fairly plagued with MSK pain most of my life and round about the same time as my PLMS first appeared, I was investigated for polyarthritis! At one time I was thinking fibromyalgia.
I"ve never thought to associate it with RLS.
There being an association between the two however does seem to suggest a common cause, but the study doesn't really go far enough to say that this is 100% dopaminergic and iron is barely mentioned.
Perhaps because of when the study was completed, there is also no mention of glutamate, the other neurotransmitter associated with RLS.
A shame because pregabalin/gabapentin used for RLS are also used for pain, nerve pain, fibromyalgia and migraines.
It's also a shame the gabàs aren't included is because the conclusion, i.e. that dopamine agonists such as pramipexole should be used to treat MSK pain is a bit terrifying!
It's bad enough it's still being prescribed for RLS, but to prescribe it for MSK pain for somebody who doesn't have RLS is worrying.
I wonder if the study had been carried out later and glutamate had been considered whether it would have suggested the gabas for MSK pain.
It begs the question, should MSK pain be included in the RLS diagnostic criteria?
I'm afraid I didn't entirely grasp the full significance of the statistics, I did study statistics, but have forgotten a lot. The answer to the question depends on the strength of the association between MSK & RLS. e.g. if everybody with RLS has MSK pain (or vice versa) then it needs to go into the criteria, but what if it's only half, a quarter, a tenth?
Just a last little thought, the study might make better sense if "musculoskeletal pain" was defined more specifically or another term used.
This is because neurotransmitters are most significant in the nervous system, NOT actually in muscles. Fibromyalgia is better known as "neuromuscular"! The "pain" actually arises in nerves but is experienced as being in muscles.
"Musculoskeletal" actually refers to muscles and bone so inflammation of these could cause MSK pain.
I came across this little study out of Canada on off label use of Gabapentin. I was curious after one of my good friends was recently prescribed it by his urologist for an overactive bladder. Hadn't heard that one before. Amazing how many conditions it's tried for when normal treatments fail. I'm glad it works for you.
"Prescribing gabapentin off label: Perspectives from psychiatry, pain and neurology specialists" ncbi.nlm.nih.gov/pmc/articl...
I thought the process of trial and error by doctors individually was the most interesting part.
----
I don't remember much pain due to growing as a kid and teen. I did have what I now know was RLS after puberty started and I do remember being told by someone that it was probably just "growing pains".
Maybe someone will undertake a more current study on MSK and any RLS correlation in both teens and adults.
Interesting that the article is suggesting that the off label prescription of gabapentin is often based on misinformation rather than evidence.
However there is evidence of it being effective for RLS at least.
I can, sort of see, the logic behind trying gabapentin for an overactive bladder.
However, whereas I know it can affect motor nerves going to the "skeletal" muscle involved in RLS, I'm not sure it can affect the nerves going to "smooth" muscle, e.g. as found in the bladder.
They are separate nervous systems, i.e the somatic nervous system (processes over which we have conscious control) and the autonomic nervous system (processes over which we have NO conscious control).
PS, I just read that glutamate, the most common of all neurotranmitters and which gabapenbtin inhibits DOES have an effect on the "sympathetic" autonomic nervous system.
It can raise blood pressure for example.
So there is SOME logic behind using it for overactive bladder
Yeah maybe. There is also fairly large sympathetic nerve that's runs to the pelvic floor musckes that can cause associated issues as well. Who knows?.I think in my reading, having trouble urinating was reported by enough people using gabapentin that the doctors turn what's a problem for some people into a benefit for others. Viagra is probably the most known example of this.
A couple years ago I was having pain with bladder and all the associated parts and functions down there for about a year. They finally diagnosed it as a tight pelvic floor. It would cause the bladder to spasm. It aslo aggravated the pudendal nerve which is sympathetic. That's when I learned all about sympathetic processes. When my pain would flare up my anxiety would go off the roof. Sympathetic nerves go both ways, hence when I was under extreme stress or anxious the problems with me undercarriage would act up. Crazy.
Wow I would be extremely careful if I were you. I speak as an ex raver who took an E called a snowball that was actually ketamine - ketamine is dangerous stuff I never touched E’s again after the experience I had. I’m now 58 and older and wiser. Please be careful there are maybe other reasons that the pharmaceuticals don’t want to use it other than that they won’t make money. It is traditionally a horse tranquiliser used by vets!
Trust me it will make depression and RLS worse and the hallucinations go on as flashbacks for years. Please please be very careful. I appreciate that RLS is a nightmare I suffer with it myself and PLMD I would rather live with the side effects of high dose Ropinirole than put myself through the HELL of ketamine
Oh yes and I live with the pain of neuropathy diabetic that is plus debilitating fibromyalgia and depression that has been with me for the 26 years since I took ketamine the depression was caused by the ketamine and yes I attempted to end it all. I am now in a wheelchair and still I would not try anything so dangerous. If I haven’t convinced you yet then you must do as you see fit but BEWARE I am just trying to protect you from crank cures!
Thanks for your concern. I will be safe under the controlled setting and dosage level. Any therapy is a risk/reward an individual must make with their medeical professional.
I stand corrected on doing some research myself I see that the NHS has used it I would not go down that road unless it was under the supervision of the NHS and even then knowing what a small dose did to me I would be very wary x
Completely unrelated, but I spilt some wild bird seed a few years ago
I burned the hemp plant that grew.
Now my vedgie patch is invaded by poppies every year. Can't get rid of them. What can I do?
My neighbor is a bit of a druggy and took ketamine to get a high and ended up in what is call a ‘K-Hole’ which was pretty scary. We found him on the floor of his apartment lounge. He couldn’t move (he was only able to talk, with difficulty) which was pretty scary for myself and my partner to see. Here is a link with a description of what he went through:
"Falling into a k-hole" is slang for how it feels when you take a high enough dose of ketamine that your awareness of the world around you and your control over your own body become so profoundly impaired that you're temporarily unable to interact with others—or the world around you.
Yep. It is quite the party drug. Special K is what it's normally called. Yeah the dose I will receive is less that what you are describing. Ketamine is a powerful anesthetic. The way they found out it worked for people experiencing suicidal ideations was by accident. Patients would be admitted to the ER with injuries that required anesthesia. Before going under many of these patients also presented as suicidal. Some patients upon waking up from surgery would report that their suicidal thoughts had lessened or had disappeared all together. This helpful side effect would often last for days, weeks and even months.
I live with anxiety, depression and thoughts of suicide everyday. If I could sleep at night these would be considerably lessened so I understand you trying everything you can. I also understand the stigma of assuring the medical establishment that our suffering is real as most RLS victims do. I’m constantly having to reassure my doctor that I’m not a druggie when I plead with him to try something new to help me (like a stronger opioid such as temgesic)
I'd just like to make a follow up statement to many if the replies to my original post. In that post I made it clear that I was seeking the Ketamine therapy for "treatment resistant depression".
I'm used to the stigma surrounding mental health but am surprised to see it pop up in this thread so often.
I don't expect anyone to understand what living with treatment resistant depression is like, unless they've experienced it themselves or through a close loved one. But it is a debilitating and life threatening condition. Thousands of people commit suicide every year, overcome by their depression.
It is an invisible condition.
So is RLS!
Everyone here gets so up in arms that no one takes their condition(RLS) seriously and at times some if us feel like we would be better off dead that suffer it anymore.
I just assumed I would expect a little more compassion from this group because if the similarities. The knee jerk negative reactions to my seeking out a possible life saving therapy seem a bit out of place here to me.
I believe nothing was intentional. But as one of the main themes on this board is increasing the awareness of the severity of RLS to those who are ignorant or dismissive , I suggest we extend that to other hard to explain conditions that suffer stigma issues as well.
There is a frustrating tendency for people to vocalise fears and/or individual bad experiences about any drug that has a 'recreational' use and it does seem to be inconsistent with many people's stated position that they would 'try anything' to gain relief. It is also often inconsistent with recorded data concerning the drug.
In your case you are taking a prescription drug under medical supervision. Furthermore, there are recorded cases where ketamine has been found to be helpful by individual rls sufferers. The fact that there are no supportive scientific studies does not render the experience of the individuals concerned less valid. What is known about rls clearly illustrates that it is an exceptionally complex condition and that it is not well understood. The case of Dr. Ignac Semmelweiss, who hypothesised about the importance of hand hygiene in maternity care in the mid-nineteenth century, is very instructive. He died ostricised and condemned in 1865 but his findings are the birth of modern practices.
I am constantly surprised by people who post that they are so desperate that they are considering self destruction but balk when kratom is mentioned because it is not a legal drug in many jurisdictions. Kratom has a proven record in treating rls and for many it has fewer side effects than opioids. It is a huge loss to rls sufferers that it cannot be obtained lawfully.
I will be very interested to hear how ketamine works for you. I have had it on my list for years as a possible treatment to try if my current drug regime fails.
Thanks. I'm guilty of it myself at times. I'm also a bit hyper sensitive to medication shaming, real or perceived, because I use Opiods for RLS.They work fairly well, but besides here I'm hesitant to share with others the relief I get from Opiods because of negative experiences.
We all have our sensitive trigger buttons.
Thanks for the well wishes on the Ketamine therapy. From what I've read most people know after just one or two sessions if it really helps with depression. They are known as super responders. Maybe I'll be one.
Hi ziggypiggy. I came across your post from 9 months ago. My doctor has suggested ketamine injections for my debilitating depression caused by stopping ropinirole after many years of use. Did you ever receive these injections? If so, did they help relieve your depression? How about RLS? Any relief there?
No. I did a couple sessions and didn't see any difference. My psychiatrist said most people will respond right away or not. At $450 a pop I decided not to go further. Didn't notice any effect on RLS but that was not my focus at the time. Depression and RLS are so hard to treat together. If you can afford it may be bv worth a try.
Thanks for your reply. That is pricy. My insurance will pay for at least a portion, I’ll have to find out how much. I’m sorry it didn’t work for you. I think I’ll give it a try. At this point I’m pretty desperate. I have tried taking Wellbutrin for the last year or so. But it gives me extreme anxiety and insomnia. Even without RLS or depression, one cannot live on 1 or 2 hours of sleep a night. But without the Wellbutrin I return to a life of suicidal thoughts. I took an SSRI for many years until I found out it makes RLS worse. I was on a high dose of Ropinirole for 16 years. I didn’t feel depressed then because my brain was flooded with dopamine. By when I finally was free of ropinirole my depression became debilitating. Good luck to you on finding some relief from your depression.
I’m sorry to hear the ketamine didn’t work for you ziggypiggy. I’m about to start a course of low dose oral ketamine therapy for my depression. Fingers crossed I’m one of the ones that it’s effective for.
Looking into it. Tried everything else. Though the last two weeks have been amazing. Added 5mg Olanzapine for sleep. My depression and anxiety have dropped dramatically. Hoping it continues. I've had honeymoon periods on medications before so I'm just going to enjoy the moment.
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Success with iron infusion (sort of)
Iron Infusion in the U.S.
Infusion how long to \"kick in\"? Hehe. 
Creativity as therapy?
New therapies for RLS!! New research finally!
