Stephanie was fine until one day at age 22 she turned to pick up something in the shower and experienced a lightning pain in her back. She had no idea what was ahead of her. An examination indicated she had the jagged and brittle spinal column of an 80-year old woman: unbeknownst to her she had severe degenerative disc disease.
A deteriorating back turned Stephanies life around
A failed discectomy on a bulging lumber disc (L-5) that left the disc oozing fluid into her spinal column led to three lower level back surgeries (discs L4-S1). An insertion of a spinal stimulator in her lower back that gave her an MRSA infection, left her in the hospital for a week (and the stimulator removed). She had a cervical spine fusion (C4-5) in August of last year to stabilize her neck.
Multiple surgeries and dozens and dozens of doctors visits later she’s been diagnosed with severe fibromyalgia, chronic fatigue syndrome (from her rheumatologist), chronic pain response syndrome and bi-polar depression/PTSD (from a violent incident three years ago).
She’s tried over the counter meds, “many, many, MANY drugs”, steroid injections, trigger point injections, physical therapy, physical exams, acupuncture, massage therapy, water therapy, discograms. Most doctors tried to give her more and more pain killers, but they only worked for a short time. After the spinal stimulator failure she had two options: pain pump or ketamine infusions.
She’s now 32 years old. She hasn’t worked since 2007.
The ketamine infusions turned out to be a godsend. She gets 800 mgs of ketamine infused for five hours a day for two days in a row. Propofol helps her sleep through the infusion cycle. She feels tired and out of sorts for about 24 hours after the infusion but her pain goes from an 8-9 every day to a 2-3 for 3-4 weeks. Then she does the infusion again.
She said ketamine has saved her life and has been “fantastic for depression”.
The Ketamine Story
The ketamine story is one of the more unusual (of the many unusual) drug stories in medicine. Developed in the 1970’s as an anesthetic, ketamine shares a classification as a “dissociative agent” (a hallucinogen) with PCP. An NMDA receptor antagonist it also interacts with opioid receptors (pain) and monoamine transporters (depression). It’s ability to produce hallucinations in some patients at anesthetic doses and it’s abuse as a recreational drug has limited its applications.
Ketamine’s ability to induce anesthesia without significantly affecting respiratory functioning made it the anesthesia of choice in the Vietnam war. It’s ability to significantly reduce pain and depression may ultimately usher in a new model of drug.
Ketamine is more and more being used to treat people with intractable pain in disorders like complex regional pain syndrome (CRPS) and depression. It appears to work by blocking NMDA receptors for glutamate. It’s dissociative properties allow patients to dissociate from the pain in their bodies.
It can cause a variety of side effects including vivid dreams, hallucinations and delirium, heart rate changes, nausea, double vision and more. Few adverse side-effects from long term use have been reported, but studies are rare and toxicity and addiction are concerns. According to one report, oral, intramuscular and intranasal ketamine preparations are also available.
Ketamine, Pain and Fibromyalgia
Ketamine use was considered in fibromyalgia as far back as 1995 when a study reported IV ketamine decreased pain intensity and increased endurance in FM patients. A 1997 study reported pain reductions in FM and a 2000 study suggested it might be getting at core issues in the disease. A 2002 review recommended ketamine be used in combination with low-dose opioids in FM. A 2011 study found that 30 minute ketamine infusions were effective in the short term but did not produce longer term effects.
Ketamine’s ability to reverse perhaps the most painful disease of all – CRPS – stimulated interest in it
The effects of ketamine on neuropathic pain have been mixed, but ketamine’s effects on perhaps the most tenacious pain disorder, complex regional pain syndrome, have been startling. Ketamine produced complete and sometimes long term remission in all CRPS patients in one study. Other placebo-controlled, randomized studies using long infusion times have produced significant reductions in pain lasting up to three months. One author has argued that fibromyalgia and CRPS share numerous similarities – including a positive response to ketamine.
One review stated that “on the basis of a few short term trials with limited clinical applications, ketamine may be effective in the treatment of chronic peripheral and central neuropathic pain, phantom and ischemic limb pain, fibromyalgia, chronic regional pain syndrome (CRPS), visceral pain and migraine”.
Depression
A single subanesthetic dose infusion of…. ketamine has been shown to have rapid and potent antidepressant effects in treatment-resistant major depressive disorder and bi-polar depression. Iadarola et. al.
The SSRI’s and SNRI’s that dominate the treatment for depression now, can take months to achieve optimal effectiveness and even then many patients do not benefit. Ketamine, on the other hand, can rapidly and potently diminish depression. It’s quick mode of action suggest possibilities as an anti-suicide drug.
Response rates in depression are around 70% and remission rates – for up to a month (but usually shorter) post infusion – are about 30%. With repeated infusions, over 70% patients remained in remission up to 83 days (with an average of 18 days).
Numerous studies have validated its effectiveness; the question now is how it’s doing what it’s doing. A large search has been underway to understand more about its glutamergic properties. At least three molecular targets have been found, and the development of new glutamatergic acting antidepressants with fewer side effects are underway.
“ In slightly more than a decade, the emergence of ketamine’s rapid antidepressant effects has been viewed by some experts in the field as arguably the most important psychiatric discovery in half a century. “ Niciu et. al.
Ketamine appears to enhance synaptic plasticity in several brain regions implicated in depression (prefrontal cortex, anterior cingulate cortex, amygdala, and hippocampus) – some of which have popped up at one time or another in ME/CFS as well.
“The initial ketamine trials have spurred worldwide interest from the pharmaceutical industry, academia, and government in developing the next generation of antidepressant medications. Niciu et. al.
Interest in ketamine effects on depression and bi-polar disorder is high and the field is expanding rapidly. The next generation of antidepressants may be ketamine-based.
- Ketamine: the Future of Depression Treatment?
- Ketamine Advocacy Network – maintains a list of doctors using ketamine
Conclusions
Ketamine’s success could spark the development of new types of pain and antidepressant drugs
The early indications are positive but the infusion requirements, the potential side effects, the unknown aspects of long term use, and the recreational abuse of this drug limit ketamine’s use at his point. Much work and perhaps a new formulation needs to be done before this drug could be considered a primary treatment for FM or most other pain disorders.
For patients with intractable, treatment resistant pain or depression , however– provided they’re able to find a doctor to prescribe it – ketamine may be a viable and perhaps not to be missed alternative.
Numerous clinical trials involving ketamine are underway and new, safer and easier formulations of the drug are in the developmental stages.
- Update! Ketamine drug approved for depression – find out more about Spravato – the first truly new approach to depression approved by the FDA in decades – and get an update on what’s going with ketamine and pain in
I seem to recall that Guaifenisen was a horse tranquilizer, is that right? I took it for years. It did something my lumps and bumps went away, cannot say that it helped with pain. It did keep tarter off the teeth, it is back now. I remember my dentist was amazed at no tarter.
I believe you are thinking of ketamine, which has been used as a veterinary anaesthetic (not specifically for horses and not the same thing as a “tranquilizer”). Guaifenesin is an expectorant and acts as a form of local stimulant. It is interesting you say it did not help your pain. I tried it as well, just because what the heck, and it did nothing. Clinical trials indicated it performs no better than placebo for pain/fibro/ME/CFS. It can be helpful if you have a persistent phlegmy cough, but that’s pretty much it. I wish we could get proper funding for proper research so we can stop self-experimenting with random unproven “treatments” that do nothing but eat up our resources and may do us harm in the long run. Ketamine at least sounds more promising and has data behind it.
I was prescribed oral ketamine by my (UK NHS) pain consultant in Spring last year, and stayed on it until the winter. It worked wonderfully for my chronic fibro pain, but, unfortunately, when I severely injured my hip, it provided no pain relief at all for it, so I had to come off it in order to take other, more effective, pain medications for my hip. It is unfortunate that it did not work for ‘new’ pain, as it was far preferable to the opioid pain relief I now take, having no noticeable side effects for me.
Interesting how pain can be produced in different ways – and respond to different drugs. It’s interesting as well that ketamine worked for your fibro pain but not the structural problems with your hip. Good luck with your hip and I hope you can get back to ketamine at some point.
I just thought I’d update this. I did go back on the ketamine, and again found it helpful, but after some months the benefit started to wear off, until I weaned myself off with no change in my pain levels. I’d say it’s good, short-term, but isn’t a long-term treatment due to this wearing off of benefit. It may depend on the dose and method of taking – I was taking an oral solution, but an alternative, higher, regular transfusion (as was used for my initial tolerance test) may give more-lasting benefit.
Thanks for the update Thia and good luck in your continuing search.
Yet another area in which Dr. Jay Goldstein was way ahead of his time. As of his retirement in 2003, ketamine was his #1 drug of choice in treating ME/CFS patients, and he had used it on more than a thousand of them. He used IV, nasal, and oral forms. Ketamine had a higher rate of success than any other drug he used. He devotes many pages in Tuning the Brain to describing its use.
Exactly, Steve. You beat me to it. I was pleased to see the title of this post and that Ketamine is getting more attention. I’m hoping to try it at the end of July. Dr. Goldstein was so way ahead of everyone it just pains me at the lack of interest in his work and methods.
Thanks for sharing, Cort.
Who knew? You guys did but I sure didn’t. That adds some real validation to the idea that ketamine works in ME/CFS because as I remember Goldstein tried everything in the book. His discovery of ketamine was the result of exhaustive searching..
Thanks for pointing that out 🙂
Dr. Goldstein gave me a ketamine infusion in 1997, after all other methods had failed to alleviate my CFS symptoms. I experienced complete remission of my symptoms for a week. Then, they slowly crept back. I tried to duplicate the effect with at home IM treatments, which helped, but never duplicated the dramatic full remission.
I wish I could find someone to try the IV infusion on me again. I use the drug on others all the time, as an anesthesiologist. It’s strange how many physicians, including anesthesiologists are afraid of this medication. It is nearly the perfect anesthetic: it produces (in high enough doses) unconsciousness, analgesia (pain relief), amnesia, and it is also an anti-inflammatory and and bronchodilator. It’s only downsides are that it raises blood pressure and heart rate (sometimes this is beneficial), and it can cause strange dreams. Some patients like the dreams. Nausea is possible with any anesthetic, and I’m not convinced that ketamine is more likely to cause nausea than any other anesthetic drug.
One important benefit of ketamine is that it can prevent or reverse opioid tolerance and prevent the onset of “opioid induced hyperalgesia” which can apparently occur when patient get infusions of short acting opioids during surgery. The analgesic and anti-tolerance effects of ketamine require very low doses, unlike those needed to achieve unconsciousness in anesthesia. I did a presentation on the use of ketamine for post-op pain control in residency, in 2004. Medicine changes very slowly; this use of ketamine is still rare.
Thanks for the article.
Hi Vlynx. Do you recall how long the infusion was that Dr. Goldstein gave you? I have a clinic here willing to do it for me but they won’t do it at Goodstein’s recommendation of 3 hours (as written in his books). They insist on 30-60 minutes which I’m very reluctant to do.
Also do you think if I did 1/4 of the dose then 30 minutes would be okay?
For the last 4 months I’ve been using Ket nasal spray for temporary (up to several hours) headache and other ME/CFS pain – prescribed by my pain neurologist. It often gives temporary relief by dropping Level 4 – 6 pain down a few notches. It doesn’t do much for Level 7 or higher. Not perfect but what is?
Just wanted to add my thoughts re Jay Goldstein. I have been following the successful trials of ketamine with a raised eyebrow- because Goldstein was a couple of decades ahead of all of it. I jst applied to participate in a trial of ketamine here in Australia for treatment-resistant depression. They didn’t allow me to to take part, due to “diagnostic complexity”. Sigh.
Anyway- here is what I posted on this topic in April 2014 regarding mood disturbance in CFS:
……………………………………………..
There is no clear answer to all of this- I have spent 18 years grappling with this question.
First, I would point out that Jay Goldstein, one of the best ever CFS clinicians, said that CFS could be ‘shoehorned into a definition of atypical or treatment-resistant depression’,
Second, we need to understand there is no distinction in real terms between ‘neurological’ and ‘psychiatric’ illness. It’s a quirk of history that the disciplines were separated. The only difference is how particular labels resonate in the public. That’s all they are- arbitrary labels.
Really- do people not think that ‘psychiatric’ or ‘mental’ or ‘psychological’ illness involves physiological dysfunction of the brain and central nervous system, just as CFS does? Do people not think that infection can cause ‘psychiatric/mental/psychological’ illness, just as it does CFS? Have a look at this if you have any doubts- a very meaningful article, due to the massive sample size and 5 decades of data.
http://www.health.harvard.edu/blog/infection-autoimmune-disease-linked-to-depression-201306176397
As good as the ICC document is, it is very wrong to downplay mood disturbance in CFS. We DO suffer from disturbed mood, and it’s not just ‘reactive’ – it’s often part and parcel of the illness, just as it is with any other physiological illness of the brain/CNS.
Incidentally, the black dog institute here in Australia has in recent years been raving about ketamine’s results in treating treatment-resistant depression in trials, saying it works in 70% of cases..and within hours of being slowly infused by IV. This was something Jay Goldstein did decades ago…for CFS…with similarly excellent results.
So- it’s true clinicians have no idea how to treat us…but that’s because their understanding of brain illness is incredibly limited…and revolves around trialling a range of antidepressants with a very narrow therapeutic means of action. They are obsessed with serotonin..where we are often more likely to respond to drugs that are dopaminergic or noradrenergic, although we often can’t tolerate them either.
I have POTS, disturbed immune function, severe PEM, temperature dysregulation, blurred vision etc. I also have depression and anxiety..and they are absolutely not ‘reactive’ due to 18 years of hellish struggle- they are part and parcel of the illness.
I have rapid therapeutic response to certain drugs due to their brain and CNS effects (such as guaiphenesin). This is probably due to its effect as an NMDA antagonist. (ketamine is also an NMDA antagonist). There may well be a primary immune dysregulation involved…or it may just be that the glandular fever that started this illness has caused brain dysfunction, and immune dysregulation is just a downstream effect, rather than a cause. Again- people with chronic depressive illness also have disturbed immune function.
Nothing is black and white – labels least of all!!!
I use a prescription Amitriptyline/Ketamine cream on my hands and feet for Erythromelalgia. I never knew exactly what Ketamine was until reading this. This was very interesting, maybe the Ketamine is also helping with my ME/CFS and Fibro.
Clarissa,
Do you just get a prescription for a branded medication with those ingredients and, if so, what is it? I thought it was still in clinical trials, for diabetic neuropathy.
No mood dioder or depression here. I see no evidence to suggest that ANS/CNS dysfunction goes hand in hand with mood disorders. Is there proven linkage in such disorders as MS?
I’ve been watching ketamine infusion/coma since learning a young physician diagnosed with Fibromyalgia went for ketamine treatment with Dr. Anthony Kirkpatrick in Florida.
There was a video of the young physician’s initial evaluation by Dr. Kirkpatrick and follow-up evals post ketamine infusion. The young physician had been an athlete participating in “extreme sports” but he was totally trashed by Fibromyalgia. He was having great difficulty working and had limited to no ability to function beyond work. The infusions seemed to work from the videos I watched but I’ve heard relapses can occur.
I’ve tried to locate the videos but I suspect they’ve been taken down given the stigma associated with Fibromyalgia and other “functional somatic syndromes”.
I was prescribed oral Ketamine for Fibro pain about 10 years ago. It did nothing for the pain. I stayed on it for one week and all it did was make me feel sleepy and “stupid” and slow …100 times worse than the brain “fog” issues I experience.
I can attest to ketamine’s effectiveness for me after using Spravato, nasal spray (esketamine) on and off for the past 18 months. I had CPTSD, ME/CFS, fibromyalgia, and treatment resistant MDD. My fibromyalgia is in complete remission, depression is 80% improved as long as neuroinflammation is controlled, and CFS is 50% or more improved, and I’ve experienced no PEM since receiving treatment for POTS these past 2 weeks. I use a scopolamine patch for Spravato treatments due to nausea and vomiting that will occur without it. I also used multiple therapies, supplements and other medications such as EMDR and biofeedback to address dysautonomia, LDN, gabapentin and Flexeril, so nothing has been a magic bullet, but trial and error and persistence have been key.
Persistence so often is the key isn’t it. I really acknowledge you for keeping on plugging on and ultimately finding some answers. Good luck with the rest of ME/CFS.
What are you doing for POTS?
Sorry I missed your email… for POTS I was given Propranolol, a beta blocker, which slowed my heart rate and most of the spikes*. This meant that I waste much less energy with that rapid heartbeat. I can do much more and still pace without PEM!
*I did have an episode of tachycardia that didn’t resolve, had cardiac ablation for atrial flutter, and it seems to have also decreased my sympathetic nervous system activation that causes hyper hydrosis, a symptom that is stopping me from looking for a part time job.
I made a successful transition from 60mg of MS-Contin(Morphine) to stimulant therapy(30mg Ritalin) for pain. My Doctor also diagnosed that my ME/CFS has a CIDP/RLS sub-component and prescribed Requip 0.25mg adjusting to 0.50mg nightly. Requip is a Ergoline medication derived from the Ergot Fungus(Hallucinigen).Two alkaloid’s of the Ergot were synthesized to create a effective Dopamine Agonist that is beneficial for nervous system disorders as well as pain related symptoms. This change in thinking toward’s pain management is changing lives and has changed my quality of life for the better. I still rely on a hydrocodone tab occasionally for breakthrough pain but usually a Motrin will do the trick. In addition to my RLS symptoms and sleep disorder’s abating the Requip has done a great job at regulating my blood pressure both high/low and relieving many deppresive symptoms, though I need to be aware of Manic behavior. I might add that the Requip also had a very strong effect on my sex drive. These Dopamine Agonist medications seem to have a very positive effect on Reward Thinking. So before one think’s about falling into the Ketamine hole, please look around at some of the other possibilities.
Where in New Zealand can I go for the treatments?
Hi Louis, did you find anyone in NZ who can offer ketamine treatment? cheers
I was so pleased to see the comments re. Dr. Goldstein. He was my doctor for about 4 years and was able to help me through the use of ketamine (iv and nasal spray). Both pain and depression improved with this regimen. Goldstein was an incredibly dedicated man who, because he was so progressive, had to deal with other medical doctors very against his protocols. I’ve had fibro for 28 years – a pretty constant companion and have tried innumerable treatments. Recently tried low dose naltrexone which has helped some people though not myself. High doses of Effexor have actually helped reduce my pain levels by about 3 points which doesn’t sound like much but which is huge experientially.
Experientially really is the key. Good to hear about Goldstein – he was a very dedicated and innovative doctor who recognized the distress people were in and went all out to relieve it. A very interesting man! Congrats on the Effexor..
Hi,
I’m a little confused, the title mentions CFS, but the article only discusses FM/Pain and depression. Any information on the benefits of Ketamine for CFS?
I haven’t read this in quite a while but while I know of people with ME/CFS who have benefited from Ketamine I don’t know of any studies or case reports on that.
Hey Cort,
I wanted to bubble this back up because there seems to be more access to treatment in the US and a bit more research in the last few years – I’m wondering if you’ve heard more about beneficial usage for me/cfs specifically?
OR am wondering if anyone has experienced any fatigue relief from ketamine?
Looks like there was a 2017 NIH study for Ketamine in bipolar patients that notes fatigue relief as a notable biproduct:
here’s that study: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4769920/
(And seems there is a new, ongoing study for me/cfs that concludes in 2023.. – I’m sure you’re already keeping tabs on that one Cort)
thanks!
Who is doing the study that is suppose to be avail in 2023?