When Medications Fail, What Next? The Perennial Problem For Neuropathy Patients

Today's post from medpagetoday.com (see link below) looks at some alternative treatments for neuropathy when standard medications have failed. It's an intelligent article from the Endocrine Society, looking at neuropathy as a whole and how it's currently treated. It goes on to explain why so many people turn to alternative treatments and supplements, often without consulting their doctor first and attemtpts to provide some evidence of their success or not, as the case may be.

Treating Chronic Diabetic Nerve Pain When Medications Fail
by Julie Maurer ENDOCRINE SOCIETY Reading Room 10.18.2017  Contributing Writer, MedPage Today

When traditional medications are not effective, patients often turn to alternative treatments
 
Expert Critique

FROM THE ENDOCRINE SOCIETY Reading Room

Peripheral neuropathy is a serious complication of diabetes. As cited here, according to the ADA more than half of people with diabetes experience some degree of nerve damage. Current treatment of diabetic nerve pain is largely based on symptomatic relief. Thus far, the only widely proven treatment strategy for improving the underlying pathologic process is strict glycemic control. Quality of life is often limited by the chronic pain patients suffer.

Evidence-based medicine supports the use of first line therapies pregabalin and gabapentin for pain relief. Duloxetine, venlafaxine, and tricyclic antidepressants have also been proven to be useful therapeutic adjuncts. Our neurology colleagues often help us with upward titration of the previously mentioned medications, and may also need to add on third-line therapies if other treatments fail to alleviate symptoms. These include Lamictal, Tegretol, Topamax, or Keppra. Pain medications can also be used, but can be addictive. All of these medications come with their own unique side effect profiles.

Given the limited efficacy of current therapeutic options, patients often turn to alternative therapies. These can include “megavitamins,” magnets, acupuncture, herbal remedies, or chiropractic manipulation. It is important to inquire about alternative therapies because many patients do not consult their physician prior to trying these treatments and the efficacy of many of them have yet to be proven. Some promising interventional therapies include: Neuromodulation or spinal cord stimulation, Thai foot massage, and botulinum toxin when compared with placebo. Topical creams are also being explored.

In addition to inquiring about patient utilization of alternative therapies, it’s important for providers to optimize nutrient status and rule out other contributing conditions to nerve pain, including B12 deficiency. Current studies exploring the efficacy of antioxidants and anti-inflammatories as a way to address the underlying pathology will hopefully help many in the future with both treatment and prevention.

Full Critique

Diabetic neuropathy pain (DNP) is a common complication in diabetes. When patients find that traditional medications are not helping their pain, some will turn to alternative treatments. It is important for clinicians to be aware what may or may not be effective in order to help patients make informed choices.

According to the American Diabetes Association, more than half of people with diabetes experience some sort of nerve damage. And, with that nerve damage comes chronic pain, for which diabetes patients are often referred to pain specialists.

"DNP is very difficult to treat, but the evidence points to starting with medications such as pregabalin or gabapentin, and adding duloxetine or venlafaxine," said Carlos Pino, MD, director of the Center for Pain Medicine at the University of Vermont College of Medicine, Burlington.

Kris Ashley, MD, a fellow in of Metabolic and Nutritional Medicine at Sutter Medical Group Functional Neurology, Auburn, California, recommends similar treatment.

"Typical treatments that most neurologists who prescribe for diabetic peripheral neuropathy as a [preventive] for chronic pain include gabapentin (Neurontin), [pregabalin] (Lyrica), tricyclic antidepressants such as amitriptyline or nortriptyline," Ashley said. She added that sometimes other medications such as These would include lamotrigine (Lamictal), carbamazepine (Tegretol), topiramate (Topamax), or levetiracetam (Keppra) if the common treatments do not work. However, these medications are often less helpful than first-line medications," she said.

Alternative treatment may provide relief

When these treatments don't work or the pain is still difficult to cope with, patients and physicians often look for other therapies.

In her review entitled "Peripheral Neuropathy: Pathogenic Mechanisms and Alternative Therapies," author Kathleen A. Head, ND, with the National College of Naturopathic Medicine, Portland, Oregon, noted that traditional medications may not always help with diabetic neuropathy pain.

"Conventional pain medications primarily mask symptoms and have significant side effects and addiction profiles," she stated in her review. "However, a widening body of research indicates alternative medicine may offer significant benefit to this patient population."

In a study conducted by Brunelli and Gorson, Division of Neurology, St. Elizabeth's Medical Center in Boston, 180 patients were questioned about their use of alternative treatments.
43% reported using complementary and alternative medicine.
Of that 43%, 48% tried more than one type of alternative treatment.
27% said their neuropathy symptoms improved with these unconventional approaches.
The treatments most often used were "megavitamins," magnets, acupuncture, herbal remedies, and chiropractic manipulation.
Almost half of those using alternative treatments did not consult their physician first.

It is important to note the number of patients who are not communicating that they are using alternative treatments. Despite the numerous studies, Pino suggested that not all alternative treatments have been proven helpful.

"If you mean alternative therapies such as non-traditional medical therapies, then it's important to know that there are not sufficient studies to support their use at this time," he said.

However, he noted that some interventional therapies do show promise.

"Neuromodulation or spinal cord stimulation have shown promising results in the treatment of DNP in selected patients. There is also some support in the literature for the use of botulinum toxin when compared to placebo," Pino said.

Nonetheless, many studies are being conducted on alternative treatments, and have been for years. "Systematic review of treatments for diabetic peripheral neuropathy" by Cakici, et al, reviewed the results of 27 different studies on such treatments, and that is just a small portion of the research in this area.

The study authors wrote: "We found that α-lipoic acid, opioids, botulinum toxin A, mexidol, reflexology and Thai foot massage had significant beneficial results."

Ashley also suggested alpha-lipoic acid, as well as some compounded creams, could be somewhat effective for chronic nerve pain.

"Capsaicin cream can be considered and is somewhat helpful; however, that can initially cause more pain with some people. Many doctors will also include higher doses of B vitamins, especially vitamin B12 (methylcobalamin) and methylfolate in the regimen," Ashley said.

For those patients for whom treatments are not working, Ashley suggested that an anti-inflammatory diet could be tried.

"Some practitioners will run blood work for micronutrient nutritional deficiencies that could contribute to comorbid nutritional neuropathies. Other contributing labs, such as inflammatory labs, can also be considered," Ashley said. "Supplements to reduce inflammation include curcumin, boswelia and N-acetylcysteine, and omega-3-fatty acids. The anti-inflammatory diet, along with extreme low carbohydrate diet, is also important to lower inflammation if present."

The study "Oxidative Stress in the Pathogenesis of Diabetic Neuropathy" by Andrea Vincent, et al, suggested that oxidative stress, caused by hyperglycemia, contributes to diabetic neuropathy.

"Therapies such as antioxidants that are targeted against oxidative stress remain our most promising approach to preventing neuropathy as well as other complications in diabetes," the study authors wrote.

When to try other treatments

Many physicians will only turn to other resources when traditional treatments do not help their patients. However, alternative treatments should be on their radar as patients may be taking supplements or trying therapies on their own as stated in Brunelli and Gorson's findings.

"Diabetic neuropathy can be very resistant to medications due to the severe damage to the nerves. Also, we need to keep in mind that all those medications mentioned have side effects that may not be tolerated by patients," said Alaa Abd-Elsayed, MD, MPH medical director, UW Health Pain Services in Wisconsin.

Pino notes there are many reasons why medications may not be helpful to the patient.

"Sometimes the medications need time to work, or the dose is inadequate or the patient may develop side effects that limit the use of the medication," he said.

Control the diabetes

As with most complications from diabetes, most can be reduced or delayed by treating the disease itself.

"Aggressive control of diabetes is very important, educate patients on the side effects that may develop if it is not well controlled, treat DNP once diagnosed to avoid its progression, collaborate with pain providers if you think traditional treatment is not working," Abd-Elsayed said.

Ashley added: "Many people are resistant to drug therapy in part due to poor glucose control, nutrient deficiencies, comorbid problems, and other toxicities that could contribute to neuropathy. Generally healthier patients seem to respond better to most therapies. It is important to try to keep patients on as little medication as possible."

https://www.medpagetoday.com/reading-room/endocrine-society/diabetes/68624