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The Fibromyalgia Drugs Your Doctor (Probably) Knows Nothing About

  [ 144 votes ]   [ 6 Comments ]
By Cort Johnson • www.ProHealth.com • July 23, 2013


Reprinted with the kind permission of Cort Johnson.

Fibromyalgia syndrome – Novel therapeutic agents. – J. Ablin and D. Buskila. Maturitas 2013

“The long term follow-up of FMS patients indicates…..that the degree of improvement achieved by many medications…is modest at best” – Ablin and Buskia

Affecting 2-3% of the population of the U.S., or about 8,000,000 people, fibromyalgia’s impact is huge; yet physician ignorance is high, with many doctors restricting their drug prescriptions to the three drugs the FDA has approved for fibromyalgia.

The Mayo Clinic – which appears to set the standard for brief, pithy and unrevealing treatment prescriptions for FM and chronic fatigue syndrome – lists just three categories of FM drugs: NSAID’s, anti-depressants and anti-seizure drugs. Adding muscle relaxants, pain relievers (tramadol, opioids) and benzodiazpines to the mix, WebMD does better, but that list, as a recent review article focusing on possible FM drugs indicated, is still far too short.

If Ablin and Buskila are right, many doctors are just scratching the surface of the drug possibilities for fibromyalgia. With all the misery present in FM, it’s not acceptable that doctors are not aware of the all drug possibilities present.

(In fact, with their emphasis on the central-nervous-system-affecting drugs, Ablin and Buskila are certainly underestimating the drug possibilities for FM as research uncovers problems in the periphery (e.g., muscles, skin, immune system) as well. The finding that small fiber neuropathy may be common in fibromyalgia, for example, shifts the treatment focus in an entirely different direction, to the immune system and intravenous gamma globulin (IVIG).)

The review article is called ‘novel therapeutic agents’ but many of the drugs in it received one or two studies in the past. These ‘novel agents’ are mostly promising drugs that need more study.

The ‘Novel’ Fibromyalgia Drugs

Norepinephrine Reuptake Inhibitors (NRI’s)

  • Esreboxetine – the dogma in FM ‘antidepressant’ use is that serotonin and norepinephrine reuptake inhibitors work better than serotonin or norepinephrine reuptake inhibitors, but two studies suggest that the NRI esreboxetine can be quite helpful. A large (n>1,000 people) randomized, placebo-controlled, blinded study found esreboxetine produced significant reductions in pain, fatigue and fibromyalgia impact scores. (Note that studies indicate antidepressants can reduce pain in people without depression.)

Dopamine Receptor Agonists

A neurotransmitter most known for its ‘reward enhancing’ factors (and the role it plays in drugs like cocaine and amphetamines), dopamine also opens up the blood vessels (a vasodilator), is an immune modulator (reduces activity of lymphocytes), reduces food flow through the gut (gut motility), reduces insulin secretion and more.

Attention deficit disorder, restless leg syndrome, Parkinson’s disease and schizophrenia have all been associated with dopamine dysfunction. Low dopamine levels are associated with many symptoms common to fibromyalgia and chronic fatigue syndrome including stiff, achy muscles, tremors, cognitive impairment, difficulty focusing, poor balance and coordination, a walking pattern characterized by talking small steps and impaired fine motor skills.

  • Pramipexole - greater than 42% of FM patients achieved a greater than 50% reduction of pain in a 2005 study. Visual analogue pain scores were reduced by an average of 36%. Lesser improvements in function and fatigue were found.

Substance P Antagonists

A neurotransmitter that increases pain, substance P levels are increased in fibromyalgia, making it (and its receptor) an intriguing drug target. (Receptors found on the outside of cells or soluble receptors in the bloodstream react with a substance (such as substance P) to initiate change (such as increase pain). Reducing substance P receptor levels would, therefore, reduce substance P’s effects on the body. Substance P antagonists have been investigated for their use in reducing nausea during chemotherapy, as antidepressants and in reducing pain. A safety review indicated they were generally safe and well tolerated.

  • Casiopitant (Rezonic) – knocks down the receptor for substance P (neurokinin-1). A Casiopitant FM trial ended in 2008 but the results have not been published.

  • Aprepitant – the review does not mention aprepitant, the only substance P antagonist used in clinical practice. New substance P inhibitors are under development.

Opioid Antagonists

“More extensive use of opioid antagonists as well as the introduction of novel microglial activation inhibitors (miRNA) pose exciting new possibilities for the treatment of FMS.” – Ablin and Buskila

It may seem strange to target drugs that knock down one of the main pain inhibiting systems in the body but the opioid receptors in many FM patients appear to filled and elevated opioid activity in the brain can cause increased, not decreased pain sensitivity.

  • Low Dose Naltrexone (LDN) – An opioid antagonist long used by people with fibromyalgia for relief, LDN finally got a clinical trial and it was successful. At the low doses used in the trial, Ablin and Busklin suggested LDN’s effectiveness in FM may have been more due to anti-inflammatory effects than to opioid antagonism.

Cannabinoid Drugs

One theory suggests the endocannabinoid system in the body is simply not up to snuff in fibromyalgia, chronic fatigue syndrome, IBS, migraine and other disorders. This major system, which is found throughout the peripheral and central nervous systems, plays a key role in pain reduction and has strong anti-inflammatory properties.

A review of cannabinoid use in non-cancer pain found that fifteen of eighteen trials “demonstrated a significant analgesic effect of cannabinoid as compared with placebo and several reported significant improvements in sleep. There were no serious adverse effects.” Cannabinoids were described as usually ‘modestly effective’ in treating neuropathic pain.

(On a personal note I’ve found medical marijuana to be effective in reducing pain, enhancing sleep and as a stress reducer.) Dr. Clauw has said he would readily swap out cannabinoid drugs/medical marijuana for opioids and other drugs if they were available. Different kinds of medical marijuana can have different effects.

  • Nabilone – is a synthetic cannabinoid often used to treat nausea during chemotherapy. Nabilone improved pain and functional capacity and reduced anxiety in FM in two studies and improved sleep (but did not effect pain in one).

NMDA Antagonists

Located in the dorsal horn of the spinal cord, the NMDA receptors are found in prime territory to regulate pain symptoms. Dorsal horn neurons receive and filter sensory information from all over the body and then transmit it to the brain. Over activation of these neurons has been shown to participate in producing hypersensitivity pain states (central sensitization). This suggests that toning down the NMDA receptors on these neurons could turn down pain levels, as well.

  • Dextromethorphan – A 2005 study indicated dextromorphan reduced a key part of the process (windup) believed to produce central sensitization in fibromyalgia. Thirty percent of FM patients responded ‘positively’ to dextromethorphan in another.

  • Ketamine – Several studies indicate Ketamine can reduce pain in fibromyalgia.  (See “Ketamine and Fibromyalgia”)

  • Memantine (Axura, Akatinol) – Studies indicating raised levels of glutamate in the insula, hippocampus and posterior cingulate cortex regions of the brains of FM patients have ignited interest in Memantine. Memantine is a new class of drug that blocks glutamate from exciting the NMDA receptors believed to contribute to central sensization…Memantine also enhances dopamine activity. A fibromyalgia memantine trial should be getting underway soon.

R-HT3 (Serotonin) Receptor Antagonists

Depending on where it’s produced, serotonin either enhances pain or diminishes it. 5-HT3 receptor antagonists attempt to diminish serotonin’s pain facilitating properties. 5-HT3 receptor blockade may also be able to reduce several immune factors that may be important in ME/CFS/FM, including TNF-a, IL-1b, IL-6 and fatty acid derivatives called prostaglandins that may be increased in ME/CFS.

  • Dolasetron – Forty-two and 28% of FM patients in one trial had greater than 30% and 50% decreases in pain. Reductions in fibromyalgia impact, anxiety and depression were not significantly different.

  • Tropisetron – Tropisetron not only helped to normalize cardiac autonomic nervous system functioning but reduced ‘pain perception’ as well in a 2007 study. Forty-five percent of patients reported having ‘good’ to ‘very good’ results in a large 2004 retrospective study. Fifty percent of FM patients in a small trial reported Tropisetron had a good or very good influence on their pain. Serum substance P levels droped in the responders. Reduced activation of brain regions associated with pain production was found in another small Tropisetron study. Forty patients of FM patients reported a greater than 35% reduction of pain in a large 2001 Tropisetron trial. The number of tender points and sleep and dizziness were significantly improved. Tropisetron also has neuroprotective, autonomic nervous system, immune modulating and sensory gating properties.

Sodium Oxybate

Sodium oxybate (Xyrem) is so unusual the authors put it in a category all its own. Approved for the treatment of narcolepsy, Xyrem is horrendously expensive but targets a key sleep dysfunction in ME/CFS/FM. Two recent studies indicated Xyrem does reduce pain and improve sleep in FM, but the FDA, citing concerns with abuse (it’s the ‘date rape’ drug) and side effects, failed to approve it, making unavailable for most in the US.

Flupirtine

A non-opioid, non-NSAID pain reliever, doctors have been using Flupirtine for over twenty years to fight pain in Europe, and it is approved in the US as an anticonvulsant. It’s not clear how Flupirtine does what it does but it appears to involve the NMDA receptors and the sympathetic nervous system. A 2010 review suggested Flupirtine may be a unique kind of analgesic agent and interest in the drug has increased recently. A study long, long ago suggested it might be helpful in fibromyalgia but no followup studies were ever done.

Expect Changes


Ablin and Buskila ended the paper on this hopeful note.

“As the fibromyalgia saga continues to unfold, novel and unexpected targets are added to the spectrum of treatments…..Indeed, FMS diagnosis and management in a decade may prove to be very different from what we know today…” – Ablin and Buskila

Source: Health Rising, July 13, 2013. By Cort Johnson.



Please Discuss This Article:   Post a Comment 

Treatments for fibromyalgia
Posted by: khch1979@gmail,com
Aug 1, 2013
I can promise you my MD knows nothing about any new treatments they haven't even heard of using magnesium and malic acid. They don't have a clue and it's a shame that they don't care to learn either, since fibromyalgia isn't real anyway right! If it wasn't for my Naprapath I would have no help at all she really cares and try's to help whenever she learns something new she tells me. I've gone to so many MDs and they just don't know anything besides antidepressants and pain killers for a so called treatment. I love Pro Health they are on the cutting edge always of new treatments and really care about helping people. My Naprapath and I both follow your site and order from you , thank you for all your help through the years and thank you for a great article . I started using neuro B12 - 2 months ago and wow what a difference from my old B12 it really is helping with energy and clearer thinking. I love taking natural cures and getting results, it's obviously something I was missing, if MDs could only grasp that concept how much better would health care be?
Reply Reply

 
Neuro B-12
Posted by: wolfhoundlady
Aug 23, 2013
Hello, I am interested in knowing what the difference is in neuro B-12. How is it ordered?

Will look forward to your responce as I have taken injectable B-12, but did not see a big difference.

Thank you.

Sheri Day

 


Thank you!
Posted by: Anne1234
Aug 8, 2013
This is my first HealthWatch email from ProHealth, first article read. I want to thank you for sending something so timely and useful for me. As a Fibro sufferer, I'm always on the lookout for new treatments and medicines to help my condition. Amazingly, you might think, so is my doctor! I can print this out and pass it along to him. He'll read it, and give me his honest opinion after doing some research. You've just become a member of my healthcare team.
Reply Reply

The Fibro Drugs your doctor knows nothing about............
Posted by: rt207
Aug 14, 2013
Wow, great article! I'll be printing this and taking it to my Pain Management doctor. He will read it and give me his opinion, but I doubt he would order anything that is out of the "norm" of what everyone else is using. Things are BAD here in Florida! For so many years, this state was known as a "pill mill" state, and in trying to stop the bad guys, the DEA and state politicians have made is extremely hard for legitimate pain patients to get proper care and meds!
I moved here from PA, and I didn't know how good I had it there! In PA, my family doctor was the leader in my healthcare team, and ordered all my meds, consullting with my Rheumy if needed. Here, you have to go to a Pain doctor for any pain meds, a psychiatrist for any nerve meds, benzodiazapines, etc., and a primary care doctor for "regular" meds, ie blood pressure, etc. All that does is make your care not coordinated, no one talks to anyone else, or knows what's going on, it's just awful.
Also, here, if the pharmacist decides that you "look" like you might be suspicious, they just tell you that they are out of whatever prescription you may have! Not one thing you can do about it either.
Maybe with more articles like the one above, more openness, and more pain patients standing up for their rights, someday we can all get the care we deserve!
Thanks for a great article, sorry to have went off on a rant there, it is just so frustrating and demeaning to not be able to get the care you need.
Hope everyone is having a not too painful day.......:)
Reply Reply

Fantastic information!
Posted by: cphero
Dec 18, 2013
As always, I am incredibly impressed with the information posted on this site. The information you posted here is information I can take to my pain doctor for further exploration.
Reply Reply

Pramipexol
Posted by: johan30
Dec 19, 2013
I am the living proof that pramipexol works positively on my fibro.
My doctor gave me pramipexol because she thought that i had restlesslegs, later on i was diagnosed fibro.
When i started with pramipexol it worked so good, i never felt that good. Because it worked so good and my doctor doesnt know why, she though that i maybe had parkinson.
But i don't have parkison.

I have also ready that dopamina-antagonist also increases growth hormone, and the more growth hormone the less fibro complaints!
Reply Reply


Post a Comment

 
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