Autonomic Neuropathy The Nerve Damage You Have No Control Over

Today's post from dressamed.com (see link below) talks about autonomic neuropathy, which may be a new term to many people. Basically, it's a form of neuropathy that affects the involuntary functions of the body, breathing, digestion, excretion, sweating, sexual function, etc. You have no control over these functions and when they go wrong thanks to nerve damage, the consequences can make life pretty miserable. Most people begin their neuropathy lives with the well-known symptoms of numbness, tingling, burning etc in the feet and/or hands and for some it stays that way but for others, the damage spreads to the autonomic functions and you begin to notice things going wrong. Your doctor will inevitably try to rule out all other other possible reasons why this is happening and it may be years before you get a proper diagnosis of autonomic neuropathy. The treatment for your pain will remain the same but you may find your medicine chest being expanded to include treatments for dysfunctions elsewhere in your body. I'm sorry, there's no sugar-coated pill to this story: if you have autonomic neuropathy it sucks but there are always ways to improve your situation but you need to take time to research and explore your options. Working with your doctor and not waiting for him or her to provide answers, is the key.

When Autonomic Neuropathy Affects Bodily Functions 
Posted on May 11, 2016 Posted in Staff Pick by Staff Pick

Do any of these symptoms sound familiar? 
 
Dizziness and fainting when you stand up
Difficulty digesting food and feeling really full when you’ve barely eaten anything
Abnormal perspiration – either sweating excessively or barely at all
Intolerance for exercise – no, not that you just hate it but your heart rate doesn’t adjust as it should
Slow pupil reaction so that your eyes don’t adjust quickly to changes in light
Urinary problems like difficulty starting or inability to completely empty your bladder

If they do, you could have autonomic neuropathy. Especially if you have diabetes, your immune system is compromised by chemotherapy, HIV/AIDS, Parkinson’s disease, lupus, Guillian-Barre or any other chronic medical condition.

You need to see a doctor immediately. A good place to start would be a physician well versed in diagnosing and treating nerve disease and damage, like your local clinician who specializes in our treatment protocol.
What Is Autonomic Neuropathy?

Autonomic neuropathy in itself is not a disease. It’s a type of peripheral neuropathy that affects the nerves that control involuntary body functions like heart rate, blood pressure, digestion and perspiration. The nerves are damaged and don’t function properly leading to a break down of the signals between the brain and the parts of the body affected by the autonomic nervous system like the heart, blood vessels, digestive system and sweat glands.

That can lead to your body being unable to regulate your heart rate or your blood pressure, an inability to properly digest your food, urinary problems, even being unable to sweat in order to cool your body down when you exercise.

Often, autonomic neuropathy is caused by other diseases or medical conditions so if you suffer from: 

Diabetes
Alcoholism
Cancer
Systemic lupus
Parkinson’s disease
HIV/AIDS

Or any number of other chronic illnesses, you stand a much higher risk of developing autonomic neuropathy. Your best course of action is not to wait until you develop symptoms. Begin a course of preventative treatment and monitoring with a clinician to lessen your chances of developing autonomic neuropathy.

How Will The Clinician Diagnose My Autonomic Neuropathy?

If you have diabetes, cancer, HIV/AIDs or any of the other diseases or chronic conditions that can cause autonomic neuropathy, it’s much easier to diagnose autonomic neuropathy. After all, as a specialist in nerve damage and treatment, your clinician is very familiar with your symptoms and the best course of treatment.

If you have symptoms of autonomic neuropathy and don’t have any of the underlying conditions, your diagnosis will be a little tougher but not impossible.

Either way, your clinician will take a very thorough history and physical. Make sure you have a list of all your symptoms, when they began, how severe they are, what helps your symptoms or makes them worse, and any and all medications your currently take (including over the counter medications, herbal supplements or vitamins).

Be honest with your clinician about your diet, alcohol intake, frequency of exercise, history of drug use and smoking. If you don’t tell the truth, you’re not giving your clinician a clear picture of your physical condition. That’s like asking him to drive you from Montreal to Mexico City without a map or a GPS. You may eventually get to where you want to be, but it’s highly unlikely.

Once your history and physical are completed, your clinician will order some tests. Depending upon your actual symptoms and which systems seem to be affected, these tests might include:
Ultrasound
Urinalysis and bladder function tests
Thermoregulatory and/or QSART sweat tests
Gastrointestinal tests
Breathing tests
Tilt-table tests (to test your heart rate and blood pressure regulation). Once your tests are completed and your clinician determines you have autonomic neuropathy, it’s time for treatment. 

Treatment and Prognosis

Our clinicians are well versed in treating all types of peripheral neuropathy, including autonomic neuropathy. They adhere to a very specialized treatment protocol that was developed specifically for patients suffering from neuropathy. That’s why their treatments have been so successful – neuropathy in all its forms is what they do.

Autonomic neuropathy is a chronic condition but it can be treated and you can do things to help relieve your symptoms.

Your clinician will work with you and your other physicians to treat your neuropathy and manage your underlying condition. They do this through:

Diet Planning and Nutritional Support
You need to give your body the nutrition it needs to heal.

If you have gastrointestinal issues caused by autonomic neuropathy, you need to make sure you’re getting enough fiber and fluids to help your body function properly.

If you have diabetes, you need to follow a diet specifically designed for diabetics and to control your blood sugar.
If your autonomic neuropathy affects your urinary system, you need to retrain your bladder. You can do this by following a schedule of when to drink and when to empty your bladder to slowly increase your bladder’s capacity.

Individually Designed Exercise Programs
If you experience exercise intolerance or blood pressure problems resulting from autonomic neuropathy, you have to be every careful with your exercise program. Make sure that you don’t overexert yourself, take it slowly. Your clinician can design an exercise program specifically for you that will allow you to exercise but won’t push you beyond what your body is capable of. And, even more importantly, they will continually monitor your progress and adjust your program as needed.

Lifestyle Modifications
If your autonomic neuropathy causes dizziness when you stand up, then do it slowly and in stages. Flex your feet or grip your hands several times before you attempt to stand to increase the flow of blood to your hands and feet. Try just sitting on the side of your bed in the morning for a few minutes before you try to stand.
Change the amount and frequency of your meals if you have digestive problems.

Don’t try to do everything all at once. Decide what really needs to be done each day and do what you can. Autonomic neuropathy is a chronic disorder and living with any chronic condition requires adaptations. Your clinician knows this all too well and will work with you to manage your level of stress and change your daily routines to help you manage your condition and your life.

All of these changes in conjunction with medications, where needed, will make it easier to live with autonomic neuropathy and lessen the chances of serious complications. Early intervention with a NeuropathyDR® clinician is still the best policy if you have any of the underlying conditions that can cause autonomic neuropathy. But if you already have symptoms, start treatment immediately.

About The Author

Dr. John Hayes, Jr. is an Evvy Award Nominee and author of “Living and Practicing by Design” and “Beating Neuropathy-Taking Misery to Miracles in Just 5 Weeks!”. His work on peripheral neuropathy has expanded the specialty of effective neuropathy treatments to physicians, physical therapists and nurses. A free Ebook, CD and information packet on his unique services and trainings can be obtained by registering your information at neuropathydr.com. To book interviews and speaking engagements call 781-754-0599.

Syndicated by EzineArticles

https://www.dressamed.com/root/autonomic-neuropathy/

HIGH SUGAR DIET NO PROBLEM FOR GENETIC MUTANTS

Imagine being able to take a pill that lets you eat all of the ice cream, cookies, and cakes that you wanted -- without gaining any weight.

New research from USC suggests that dream may not be impossible. A team of scientists led by Sean Curran of the USC Davis School of Gerontology and the Keck School of Medicine of USC found a new way to suppress the obesity that accompanies a high-sugar diet, pinning it down to a key gene that pharmaceutical companies have already developed drugs to target.

So far, Curran's work has been solely on the worm Caenorhabditis elegans and human cells in a petri dish -- but the genetic pathway he studied is found in almost all animals from yeast to humans. Next, he plans to test his findings in mice.

Curran's research is outlined in a study that will be published on Oct. 6 by Nature Communications.

Building on previous work with C. elegans, Curran and his colleagues found that certain genetic mutants -- those with a hyperactive SKN-1 gene -- could be fed incredibly high-sugar diets without gaining any weight, while regular C. elegansballooned on the same diet.

"The high-sugar diet that the bacteria ate was the equivalent of a human eating the Western diet," Curran said, referring to the diet favored by the Western world, characterized by high-fat and high-sugar foods, like burgers, fries and soda.

The SKN-1 gene also exists in humans, where it is called Nrf2, suggesting that the findings might translate, he said. The Nrf2 protein, a "transcription factor" that binds to a specific sequence of DNA to control the ability of cells to detox or repair damage when exposed to chemically reactive oxygen (a common threat to cells' well being), has been well studied in mammals.

Pharmaceutical companies have already worked to develop small-molecule drugs that target Nrf2, in hopes that it will produce more anti-oxidants and slow aging.

Though the promise of a pill to help control your body's response to food is enticing, it is not without risk, Curran said. Increased Nrf2 function has been linked to aggressive cancers.

"Perhaps it is a matter of timing and location," Curran said. "If we can acutely activate Nrf2 in specific tissues when needed then maybe we can take advantage of its potential benefits."

rhNGF no its not a misprint

If you have been surfing the web looking for useful information about neuropathy, you may well have come across the unusually named, rhNGF as one of three proven effective treatments for neuropathic pain and problems. The other two are cannabis and capsaicin and have been extensively covered on this Blog but rhNGF is for most people, a complete mystery and when you try to research it on the Net, you can understand why!

Recombinant human nerve growth factor (rhNGF) is regarded as the most promising therapy in decades, for neurodegeneration of the central and peripheral nervous systems as well as for several other pathological conditions involving the immune system. However, rhNGF is not commercially available as a drug. For a start, it hasn’t been approved by the major, international medical authorities as yet, so any discussion at the moment is pretty much irrelevant but its day will come and it will be useful to have some idea of what it is and what it does.

At this point it might be advisable to avoid all websites ‘selling’ this as a product. It’s one of those things that attracts health and fitness fanatics, (like anabolic steroids for instance although there is absolutely no connection)and I have no idea why but because the national organisations haven’t as yet approved it for neuropathy treatment... you know the story for HIV patients... throwing any doubtful ‘variable’ into the mix is rarely advisable.

Giving a simple definition of rhNGF, is however, easier said than done because it is an extremely complex chemical structure. I certainly don’t understand much about it but will attempt here to simplify the information available on the Net. If you know better, or have any information to offer, please use the contact form at the top of the page, to put us all better in the picture.

First of all, the letters stand for Recombinant Human Nerve Growth Factor. ‘Recombinant means the new entity (e.g., gene, protein, cell, individual) that results from genetic recombination.

In short, NGF is a protein that is involved in the growth of peripheral nerve cells and was discovered 50 years ago as a molecule that promoted the survival and differentiation of sensory and sympathetic neurons. It is a small secreted protein that is important for the growth, maintenance, and survival of certain target neurons (nerve cells). It also functions as a signalling molecule.

While "nerve growth factor" refers to a single factor, "nerve growth factors" refers to a family of factors also known as neurotrophins. Neurotrophins represent an important family of regulatory proteins essential for sensory nerve development. Several neurotrophins have been identified, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin 3 (NT3). NGF is one of the most studied neurotrophins. It is a key regulator of sensory neurone excitability and an important mediator of injury-induced nociceptive and neuropathic pain.

It is an immensely complex biological process for the layman but NGF ‘s have shown very promising results in animal studies. Recombinant human nerve growth factor (rhNGF) has been in phase III trials (essentially meaning it's taken seriously!) and the results are also extremely encouraging.

Particular attention is given to a growing body of evidence that suggests that among other roles, NGF signalling, aids neuroprotective and repair functions. The analysis points to many interesting unanswered questions and to the potential for continuing research on NGF to substantially enhance our understanding of the mechanisms and treatment of neurological disorders.

The administration of nerve growth factor (NGF) has been found to prevent neuropathies induced by anti-cancer drugs such as cisplatin, vincristine and taxol. However, it is clinically important to know whether NGF is beneficial once the neuropathy is already established and this is one of the reasons why medical authorities are not yet ready to approve commercial drugs. It’s something with great potential and something which will require a lot more research and assessment.

Regarding our own situation as HIV patients with neuropathy, recombinant human nerve growth factor (rhNGF) was used in a multicenter, placebo-controlled, randomized trial by Justin McArthur of Johns Hopkins University and colleagues to evaluate its efficacy as a treatment for HIV-associated peripheral neuropathy. Nearly 300 individuals were randomized to receive two different doses of nerve growth factor or placebo. After 18 weeks of randomized treatment, there was a significant difference in average and maximum pain intensity favouring rhNGF. However, there were no differences in terms of mood, analgesic use, or epidermal nerve fibre density between the groups.

Giovanni Schifitto of the University of Rochester and colleagues reported on data from the 48-week open-label phase of the rhNGF study described above. After the randomized phase, 200 of the 235 eligible patients continued taking either 0.1 or 0.3 mcg/ kg of rhNGF. Neurological and quantitative sensory testing was performed at baseline and at week 48. Consistent pain improvement was observed in all groups, with the high-dose recipients demonstrating better outcomes than low-dose participants.

I'm sorry, I don't understand enough about it to be able to describe it more simply and for once, research on the Web leads you to very complicated scientific journals and papers which are way above my head. So why write a post about it you may ask? The reason is that a) you will probably see it mentioned in passing (but not in detail) and b) if it is one of three things they are pretty sure about, then it's only a matter of time before it becomes available in an approved format. It's a treatment for the future then and the more questions patients ask, the more likely the whole treadmill will turn more quickly, to everyone's benefit.

Good luck looking for information and if you do find something useful to share with us, please do - knowledge is always power, especially concerning medical issues.

Theres No Magic Bullet For Neuropathy Vid

Although this short video from beatingneuropathytv (see link below) is clearly an advertisement for Dr. Hayes' own site and although this blog makes a point of not advertising services or private companies, what he says here is vitally important for people living with neuropathy. There is no 'quick fix' despite what you may hear about this cure or the other, they don't exist. Neuropathy is a complex disorder for which there is currently no cure. Your symptoms may be helped according to what you take and according to what's appropriate for you in your particular case but there is no cure for nerve damage as a general rule. This means that you have to work your way through the myriad of possibilities until you find something that works for you in reducing your symptoms. This has to be done in collaboration with your doctor or specialist but you can also help yourself greatly by doing the research, especially in the field of supplements. You also need to be very aware of the side effects and efficiency of whatever chemical drug you've been prescribed and discuss these with your doctor. If something is not working after a few months (or even less in some cases) you should be moved on to the next option. In the standard treatment of neuropathy, there are about ten drug treatments and several options within each one of those. Creating a partnership with your doctor is important and if your doctor is unwilling to do that, it may be wise to move on to another (just as with the medication). Looking through the alphabetical list to the right of this blog will inform you of the standard course of treatments for neuropathy and give you lots of information to take to your doctor's appointment with you.



Episode 33 – There Isn’t A Magic Cure  
Posted by John Hayes Jr Thursday, November 7th, 2013
 
Dr. Hayes talks about the importance of an integrated approach to fighting Neuropathy and Chronic Pain, and how clinic experience tells us drug-only treatment is almost never the answer! As experience tells us day after day, this is the ONLY approach with any lasting hope of return to health!



http://beatingneuropathy.tv/2013/11/episode-33-there-isnt-a-magic-neuropathy-cure/

Medical Marijuana Versus Opioids A No Brainer

Today's post from blogs.jwatch.org (see link below) takes the view that it's now time to seriously consider using medical marijuana as an alternative to the opioid pain killers so many neuropathy patients (and other chronic pain sufferers) need. If there is genuinely a health crisis caused by opioid abuse among genuine subscribers (as the media insists) then we really need to start appreciating what we already have in the locker and stop attaching moral stigmas to marijuana, that are decades out of date. There is now more than enough evidence that marijuana truly works for people living with nerve damage pain, so as the article states...'legalise it already'! In that way, the health authorities can take control of the situation, control the quality and the costs and cut out the middle men dealers. Yet still people with absolutely no knowledge of the science look at marijuana as being the spawn of the devil and equal in its evil effects to opioids themselves (which are by the way, very effective if taken as prescribed and controlled by a specialist doctor or pharmacist). It's time to destroy the myths about marijuana. Well worth a read!

Medical Marijuana and Painful Neuropathy — An Opportunity to Make Us Believers 

By Paul E. Sax, M.D.

From Journal WatchJanuary 10th, 2016
 
Medical marijuana is now officially available in New York, the city with by far the largest number of people living with HIV/AIDS in the country. Reporting on the first dispensary in Manhattan, the aptly named Julie Weed (yes! her real name!) writes:

One of the most promising areas for research is the substitution of medical marijuana for opioids like OxyContin and Percocet for pain management …“68% of our patients with AIDS-related neuropathy have said that medical marijuana has allowed them to stop taking opioid prescription pain killers which can be addictive, cause a variety of harmful side-effects, and — most critically – are the cause of thousands of overdose deaths per year.”

Some thoughts based on this claim, and the long history of medical marijuana and HIV/AIDS: 

Could 68% of patients with painful peripheral neuropathy really stop opioid pain killers with marijuana? Wow. If that’s true, it’s huge — even half this rate would be a dramatic advance. Among the most frustrating conditions in all of medicine, painful peripheral neuropathy has a list of treatments as varied as the products sold in the “Cough and Cold” aisle at your pharmacy — and are, unfortunately, about equally effective. Proven strategies to help people come off chronic narcotics are badly needed. 

HIV specialists have been hearing about the medical use of marijuana even longer than we’ve had effective antiretroviral therapy. Initially touted as an appetite stimulant for HIV-related anorexia and weight loss, and as palliative therapy to ease the pain of death and dying, it gained further use in the mid-1990s when early HIV-related combination regimens caused so much nausea. This randomized clinical trial led by Donald Abrams — who has done some of the best work studying marijuana in HIV against great odds — found that 5 days of smoked cannabis was more effective than placebo in 50 patients with painful peripheral neuropathy. Of course blinding the study arms was (and remains) essentially impossible given the euphoric effects of the drug, but maybe that’s the whole point. 

Just legalize the stuff already. That’s how I’d characterize the opinion on marijuana for the vast majority of the doctors, nurses, and social workers I work with, some of whom (like me) both remember Woodstock (the original one, kids) and enjoy the music from it, or are younger, and have the same view. If marijuana is legalized, it can be more easily regulated, taxed, and studied (see below) — just like that other legal psychoactive drug, alcohol. Seems like this is hardly a minority view (the link is to the source of the graphic at the top of the page). 

Legalization would allow more rigorous studies of therapeutic use, long-term effects, and safety. Such studies are now essentially prohibited by the federal government since marijuana is considered a drug of abuse. As a result, many claims about its medical indications are based on either small, short term, or methodologically questionable studies or, even worse, strongly-held beliefs based mostly on anecdote — the weakest form of scientific evidence. That is, I’m afraid, what that “68% have stopped their opiates” claim is from the opening paragraph. Until it’s studied more rigorously, we’re stuck with the frustration of dealing with claims that marijuana is a valid treatment for practically every chronic condition under the sun. A similar claim might be made of benzodiazepines like Valium, Xanax, and Klonopin — which definitely make people feel better — but clinical research has more clearly defined both the benefits and risks of this drug class. 

The quasi-medical atmosphere of some marijuana dispensaries is a huge negative to the acceptance of legitimate medical use. Got a free 10 minutes? That plus saying you have “insomnia” gets you a weed license for the medical stuff in Venice, no medical records required. Medical marijuana exists in this bizarre parallel system to “real” FDA approved drugs, and the absence of good scientific data means that the indications for use state-by-state are literally and figuratively all over the map. Got to love this indication (and I use the word loosely) for medical use from California: “Any other chronic or persistent medical symptom that substantially limits the ability of the person to conduct one or more major life activities (as defined by the Americans with Disabilities Act of 1990) or, if not alleviated, may cause serious harm to the patient’s safety or physical or mental health.” If it’s based on patient report, that covers pretty much anything, doesn’t it?

So what’s my take right now? Count me in the same camp as these authors, who published their views in a JAMA editorial last year, writing:

If the states’ initiative to legalize medical marijuana is merely a veiled step toward allowing access to recreational marijuana, then the medical community should be left out of the process, and instead marijuana should be decriminalized … Evidence justifying marijuana use for various medical conditions will require the conduct of adequately powered, double-blind, randomized, placebo/active controlled clinical trials to test its short- and long-term efficacy and safety. The federal government and states should support medical marijuana research.

Totally agree. Meanwhile, here’s a study design free for the taking:

Title: A randomized, blinded study of cannabis versus placebo to reduce opiate use in HIV-related neuropathic pain.

Entry criteria: Painful HIV-related neuropathy for ≥3 months, confirmed by a neurologist at screening, and requiring the use of opiates for control. Stable doses of opiates for at least 4 weeks prior to screening are required. HIV RNA must be < 50 copies/mL on non-neurotoxic containing ART.

Intervention: Smoked cannabis or placebo for 24 weeks; up to daily use as desired by study subjects. Adjunctive therapies (gabapentin, antiepileptics, non-steroidal anti-inflammatory drugs, acupuncture) will be administered at the discretion of the investigators.

Primary endpoint: Time to cessation of opiate use as estimated by the Kaplan-Meier method.

Secondary endpoints: Time to reduction in 25, 50, and 75% of opiate use; absolute and relative reduction in opiate dose. Proportion opiate free at study completion. And what the hell, might as well also do Numeric Pain Rating Scale, Change in Pain Inventory Score, Numeric Rating Scale Sleep Interference Score, Medical Outcomes Study Sleep Scale, Patient Global Impression of Change of Pain, and all those other neuropathy assessments. Throw in some neurocognitive testing just for fun.

Funding: National Institutes of Health

You’re welcome!

Let’s see if what you think.

What should we do with marijuana?

Legalize, regulate, and study it like alcohol.
Decriminalize and study it, and reserve for medical use only, like benzodiazepines.
Leave things as they are now.

View Results

http://blogs.jwatch.org/hiv-id-observations/index.php/medical-marijuana-and-painful-neuropathy-an-opportunity-to-make-us-believers/2016/01/10/

Comparing Neuropathy Drugs Finds No Winner

Today's post from medscape.com (see link below) looks at the research into neuropathy drugs done by researchers in South Dakota. It concludes that there is no single drug that works significantly better than any other (something experienced neuropathy patients could have told them from the off) and once again, suggests that if that's the case, then cheaper options may be better. This blog warns against that sort of thinking which may lead to patients being sold short in favour of saving money. However, it is refreshing to read comparisons between drugs and their effectiveness, especially if they are based on factual research. The drug companies may not be too pleased to see their drugs being placed below others on a scale but for the patient, this sort of disclosure is what we need.

No Clear Winner for Relief of Diabetic Neuropathy Pain 
Medscape Medical News Pam Harrison November 13, 2014

A new comparison of the effectiveness of different analgesic medications used for the treatment of diabetic neuropathy pain has not identified any clear winner.

Rather, several analgesics from different pharmacologic classes — serotonin-norepinephrine reuptake inhibitors (SNRIs), anticonvulsants, tricyclic antidepressants (TCAs) and topical capsaicin 0.75% — seem to be effective for the short-term management of this condition, say the researchers, led by Dr Marcio Griebeler (Sanford Health, Sioux Falls, South Dakota).

The comparative effectiveness of these agents also remains unclear, they say.

"We have four drug classes that are clearly better than placebo, but comparing them head-to-head is difficult to do, and we don't have a lot of good information as to which drug might be better," agreed Dr Brian Callaghan (University of Michigan, Ann Arbor, Michigan), who coauthored an accompanying editorial.

"I don't use capsaicin much because of the side effects, but the other three drug classes all have comparable evidence of their efficacy, so my thoughts about them come down to comorbidity, side effects, and maybe most important, cost," he told Medscape Medical News.

Dr Griebeler said the question she and her coauthors sought to answer was whether there is any medication that is better than any others for diabetic neuropathy. "Since very few studies were head-to-head comparisons, we had to do indirect comparisons using placebo as the comparator agent, and when we did this, some drugs were a bit better than others, but there wasn't a huge difference between them, so we cannot make a strong recommendation for any of them."

The research was published in the November 4, 2014 issue of the Annals of Internal Medicine.

Randomized Controlled Trials and Head-to-Head Studies Needed

Dr Griebeler and colleagues analyzed a total of 65 randomized controlled trials involving 12,632 patients in which 27 pharmacologic interventions for diabetic neuropathy pain were evaluated.

Out of these, nine head-to-head trials were identified in which medications from different pharmacologic classes were compared.

"In general, trials were brief (mean follow-up, 14 weeks) and enrolled mostly middle-aged men who had type 1 or 2 diabetes for more than 5 years," the authors observe.

Expressed as a standard mean difference (SMD) in pain relief, results from these nine head-to-head trials indicated that the SNRIs and the TCAs reduce pain more effectively than anticonvulsants (SMD, -0.34) and topical capsaicin 0.75%.

Because of the few head-to-head studies, Dr Griebeler and colleagues then used a network meta-analysis to indirectly compare drug classes. Although they found that SNRIs are more effective than anticonvulsants and TCAs are better than topical capsaicin, results of other comparisons among these four categories of medications did not significantly differ.

In conclusion, "evidence is scant, mostly indirect, and often derived from brief trials with an unclear or high risk of bias."

"Our network meta-analysis therefore has implications for future research efforts and highlights the need for properly designed randomized controlled trials and more head-to-head comparisons of the most commonly used medications for painful diabetic neuropathy (that is, amitriptyline, gabapentin, pregabalin, and duloxetine)."

Only Pregabalin, Duloxetine Approved for Painful Diabetic Neuropathy

Dr Griebeler and colleagues also note that varying recommendations for the management of painful diabetic neuropathy have been proposed.

The European Federation of Neurological Societies recommended in 2010 that tricyclics, gabapentin, pregabalin (Lyrica, Pfizer), and SNRIs (including duloxetine and venlafaxine) should be used as first-line agents. Tramadol or stronger opioids are considered as second- or third-line medications.

In 2011, the International Toronto Expert Panel on Diabetic Neuropathy proposed similar recommendations, while the American Academy of Neurology recommends offering pregabalin as a first-line option, whereas venlafaxine, duloxetine, amitriptyline, gabapentin, valproate, opioids (morphine sulfate, tramadol, and controlled-release oxycodone), and capsaicin should be considered later.

The doctors note, however, that only pregabalin and duloxetine are approved by the US Food and Drug Administration and the European Medicines Agency for the treatment of neuropathic pain in diabetes.

Cost May Be Deciding Factor

In their accompanying editorial, Dr Callaghan and colleague Dr Eva Feldman (University of Michigan, Ann Arbor), wonder, "Which medications should physicians prescribe while we wait for more definitive evidence? Unfortunately, current guidelines and the US FDA are less helpful to busy clinicians than one might hope."

They point out one of the marked differences among the medications used for the treatment of diabetic neuropathy is cost.

As Dr Callaghan observes, gabapentin and pregabalin both have the same mechanism of action and do the same thing to relieve painful diabetic neuropathy. "Yet one (gabapentin) is 10 times cheaper than the other," he points out.

Meanwhile the cost of venlafaxine, though now available generically, remains high and is not much less than the cost of duloxetine, until recently a patented drug.

"The tricyclic antidepressants have been around forever," Dr Callaghan added, "and while their market share has decreased over the years, they are probably some of our best medications and certainly the cheapest for neuropathic pain."

The approval of pregabalin and duloxetine for the treatment of painful diabetic neuropathy has given these two agents more prominence than the others, and perhaps an unfair market share, Dr. Callaghan suggested.

"I'm a neuromuscular physician with a special interest in neuropathy, so this is something that I deal with all the time," he remarked.

"I think cost is a big component in our choice of medication — both out-of-pocket costs for patients and then everybody's premiums having to go up if we are not careful [about] how we manage our resources. So if the medicines are the same, why not use the cheaper ones?

"Given the current price of these medications, we believe that the most cost-effective approach is to try one or more TCAs as first-line medications, followed by gabapentin. The high-cost options of venlafaxine, duloxetine, and pregabalin should be reserved for when these other medications have failed."

The study was funded by the Mayo Foundation for Medical Education and Research and Clinical and Translational Science Awards. Dr Griebeler and coauthors have reported no relevant financial relationships, nor have Dr Callaghan and Dr Feldman.

Ann Intern Med. 2014;161:639-649, 674-675. Abstract, Editorial

http://www.medscape.com/viewarticle/834877#vp_2