+100%-

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 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 - fibromyalgia

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.

Conclusions

ketamine's success in pain

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

A Ketamine Revolution for Depression and Pain? Spravato, Fibromyalgia and ME/CFS

 

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