RSD/CRPS, Multiple Sclerosis, LDN & Ketamine


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It is rare for me to see a patient who is not complex.

They have failed so many treatments for so many years before they call.

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This is the report of a lovely woman in her early 70’s with progressive Multiple Sclerosis for 30 years and paraplegia that has forced her to use an electric scooter the last 5 years, and power wheelchair the last 2o years. Because of total paralysis of the right lower limb, she fell and shattered her femur, the thigh bone, in August 2009. Tragically, and all too often, the surgeon failed to diagnose Complex Regional Pain Syndrome [CRPS], even failed to visit her in the hospital. CRPS increased the fatigue she had already had from Multiple Sclerosis.

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Thankfully a physical therapist suggested the diagnosis.

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Why is pain management not a required subject for physicians?

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I have written elsewhere that the American Pain Society discovered that our National Institute of Health, NIH, devotes less than half of 1% of their research dollar to pain research. Of 28 NIH institutes, none for pain, three for addiction. This will not change soon. The only hope is that RSDSA.org will succeed in collaborating with all pain organizations, groups with dystonia, chronic fatigue in order to give a voice and research dollar to advances.

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Before seeing me in September, she had 11 sympathetic blocks with no benefit.

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Does it make you wonder why 11 were done?

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How does insurance authorize 11 when 10 had no benefit? I have just learned that a doctor must indicate at least 50% relief before another will be authorized. That explains it.

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Then she was given opioids including tramadal and Butrans patch which rendered her a “zombie,” sedated, poor memory, unable to function. She tried 4 or 5 treatments of Calmare with no benefit but was advised she needed a clear neural pathway for it to work. That was not possible due to the Multiple Sclerosis.
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Lyrica caused severe edema. Gabapentin 1400 mg/day caused weight gain, increased her appetite  more than usual, but she remained on it. She craves sweets more than usual, at times uncontrollably. Perhaps it can be slowly tapered now. Advil 600 mg gave some benefit but caused ulcers that required Nexium.

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Since her initial visit a few weeks ago, she became 60% better during her two week stay.

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I will highlight only two of the new medications started.

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It may also be said that opioids are not the answer.

Opioids may perpetuate pain.
They may produce paradoxical pain or opioid induced hyperalgesia or windup.

They may block the effect of ketamine and other adjuvants that would otherwise lower pain.

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Of importance is that she was not able to tolerate clothing on her right lower limb for three years, not even a sheet, and now she is able to sleep through the night without pain for the first time in three years and able to wear a skirt. This allows her to go out with family to restaurants and even to enjoy shopping with her daughter. Her dose of ketamine is very small relative to most of my patients and she uses it only once or twice a day since most of the new medications have brought her pain down.

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At her first visit one month ago, she rated pain from 6 to 8 on a scale of 10, average 7/10. Now 60% better, ranging from zero to 7, average 4. Yes zero pain, sleeping through the night without pain and waking without pain. She had not been able to tolerate touch to the right thigh or foot and would pull her skirt above the thigh, removing her shoe.

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Now she indicates pain continues to improve.

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Of interest, despite an abundance of concern that low dose naltrexone [LDN] may flare her Multiple Sclerosis, we were easily able to increase the dose to triple what is usually called “LDN.” This did not flare her condition and may be one of the most effective medications she is taking for pain.

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What is LDN?

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The FDA has sanctioned its use in the USA only in doses of 50 to 400 mg for addiction to opioids and alcohol.

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Low dose naltrexone [LDN] is a fascinating medication. It has been used in low dose in persons with Multiple Sclerosis since 1985 when a Harvard trained neurologist in New York City, Dr. Bihari, first discovered that it relieved all disability in some patients with Multiple Sclerosis and prevented recurrent attacks. Since then, doctors in Scotland, where they have the highest incidence of Multiple Sclerosis, find that one of the earliest signs of recovery in this population is relief of neurogenic bladder. It is said that persons with Multiple Sclerosis must remain on LDN for 1.5 years before they might fully assess its value.

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 Multiple Sclerosis may be flared unless very small doses of LDN are used.

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Many with Mulitple Sclerosis cannot tolerate more than 2 or 3 mg, perhaps due to spasticity. There is a great deal of dogma on the web about its mechanism, dosing and timing for off label use. Use the search function on this site to review the prior discussions I posted on LDN, MS, CRPS.

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Naltrexone is a glial modulator.

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What’s that?!

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By serendipity, four years ago I discovered naltrexone in low dose may relieve chronic intractable pain. I had been using it for perhaps eight years in microgram doses but I found in milligram doses it is even more profound.

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The mechanism of naltrexone and a wee bit of glial research is discussed here. The Nobel Prize was awarded last year for the discovery that these glia are your innate immune system. They are profoundly important in many diseases including chronic pain, Major Depression, Multiple Sclerosis, Alzheimers, Parkinsons Disease, ALS, Autism. They produce inflammatory cytokines that lead to inflammation.

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Now that she has been home for two weeks, on a number of medications that I started, not just the ketamine and LDN, I hope she will comment on her experience and her progress since flying back to the east coast after her brief visit here.

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It is often essential to taper off opioids to allow other medication to work.

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I feel she was able to benefit from these low doses of medication because she tapered off all opioid medication prior to her visit, thus allowing her system to recover and respond to these medications. We will know more in the next few months as she slowly titrates up on some of the medications that were started.

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Next year on her return, we may be able to withdraw some of the medications depending on how well she is doing.

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Finally, ketamine does cause her to have brief side effects. Her husband likens the effect the same as half a glass of wine: “She’s really cute.” Thankfully, most people have no side effects and if they do, they rarely last more than 20 minutes.

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She sends an update below, 80 to 90% better. Hopefully this will continue to improve over the next months as she slowly increases the medication we started. And ketamine has an additive effect in some. It is anti-inflammatory.

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The material on this site is for informational purposes only.

It is not a substitute for medical advice, diagnosis or treatment provided by a qualified health care provider.

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Please understand that it is not legal for me to give medical advice without a consultation.

If you wish an appointment, please telephone my office or contact your local psychiatrist.

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For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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Ketamine Rapidly Relieves Depression by Restoring Brain Connections


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This research is one of the most dramatic findings in the field of depression and mood disorders. It was published in Science by researchers from Yale and the National Institute of Mental Health, discussed by PBS here.

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The speed with which ketamine can relieve major depression is deeply moving to witness. In my experience prescribing nasal ketamine it works almost 100% of the time. I have discussed ketamine and previous publications on it for Major Depression and PTSD. It is also effective for suicidal and bipolar depression patients.

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Ronald S. Duman, PhD, the lead scientist, reviews his group’s research in this 2011 video:

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Stress and depression leads to structural changes in the brain and these structural changes are reversible.

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Depression affects 17% of the population, almost one in five of the population. Only one third of patients are effectively treated by existing antidepressants, even after many weeks. Nerve growth factors, in particular BDNF, are decreased by stress, with a very significant loss in depressed patients. BDNF produces antidepressant behavior in rodent models of depression.

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BDNF is important for influencing the survival and function of neurons.

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There are certain neurogenic zones in the brain that produce new neurons. Stress decreases the number of new neurons. Chronic antidepressant use increases the numbers and proliferation of these new neurons. Antidepressant treatment increases neurogenesis and this is dependent upon BDNF, this neurotrophic factor.

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[His slide shows] Exercise, Prozac, ECT, antipsychotics, antidepressants increase neurogenesis.

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Not only are there more synapses made by ketamine, but they are a larger size which is indicative of ones that are more functionally connected. Antidepressants take many weeks. A single dose of ketamine rapidly reverses depressive behaviors and loss of connections and completely reverses the decrements that had occurred over several weeks.

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In suicidal patients given ketamine at Yale in the Emergency Room, within a matter of hours, the suicidality is completely reversed. These people are better for weeks after a single dose of ketamine treatment. [emphasis mine]

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Therapeutically ketamine is even more rapidly acting than ECT.

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Ketamine increases BDNF. But research shows its effects are blocked in mice that are deficient in BDNF. Riluzole also influences BDNF, but the side effect profile is so serious that I would not consider prescribing it without more data on safety.

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Safety concerns are often raised in publications regarding chronic ketamine use. Most of my patients have no side effects at all. It is one of the safest medications we have and only a small percentage experience transient side effects. The favorable side effect profile, simplicity and low cost is key. The results for nasal ketamine are not 100%, neither is IV ketamine, but I have patients who respond to nasal spray when they failed IV ketamine. More importantly, they can carry it in their pocket and use as needed.

 

My experience prescribing ketamine goes back almost to the year 2000 for persons with chronic pain who have used ketamine several times daily, and since Spring 2012 for Major Depression. Its effect for depression lasts longer than for chronic intractable pain where it is short lasting. In the past, I prescribed it orally, by mouth, but since late 2011 I have prescribed it in a nasal spray and that form works for depression.

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The neuroprotective action of ketamine has been published since at least 1988.

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Patients can use nasal ketamine as needed. Schedules vary, everyone is different. It is short acting, but it does not stop working.

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However, the use of other adjuvants, such as glial modulators, in treatment of depression is essential to understand, and is now work in progress. The role of inflammation and glia in the pathogenesis of depression has been well established since 2000, and discussed here.

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Does ketamine also restore brain connections in patients with chronic pain? Chronic pain and major depression both lead to brain atrophy and memory loss. Both cause the same imbalance in glial cytokines. Both may respond to glial modulators, e.g. low dose naltrexone among others that have worked in some patients.

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“The original link between ketamine and relief of depression was made at the Connecticut Mental Health Center in New Haven by John Krystal, chair of the department of psychiatry at Yale, and Dennis Charney, now dean of Mt. Sinai School of Medicine, who helped launch clinical trials of ketamine while at the National Institute of Mental Health,” reported by Yale  here.

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I hope to add new approaches to treatment of anxiety that has failed to respond to other interventions.

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The material on this site is for informational purposes only, and is not a substitute

 for medical advice, diagnosis or treatment provided by a qualified health care provider.

~

Please understand that it is not legal for me to give medical advice without a consultation.

If you wish an appointment, please telephone my office or contact your local psychiatrist.

~

For My Home Page, click here:  Welcome to my Weblog on Pain Management!

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