Diabetic neuropathy medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Despite advances in the understanding of the metabolic causes of neuropathy, treatments aimed at interrupting these pathological processes have been limited by side effects and lack of efficacy. Thus, with the exception of tight glucose control, treatments are for reducing pain and other symptoms and do not address the underlying problems.

Agents for pain control include tricyclic antidepressants (TCAs), serotonin reuptake inhibitors (Selective serotonin reuptake inhibitor/ SSRIs) and antiepileptic drugs (AEDs). A systematic review concluded that "tricyclic antidepressants and traditional anticonvulsants are better for short term pain relief than newer generation anticonvulsants."

Medical Therapy

Tight glucose control

Treatment of early manifestations of sensorimotor polyneuropathy involves improving glycemic control. Tight control of blood glucose can reverse the changes of diabetic neuropathy, but only if the neuropathy and diabetes is recent in onset. Conversely, painful symptoms of neuropathy in uncontrolled diabetics tend to subside as the disease and numbness progress. Of course, these uncontrolled patients are at great risk for diabetic foot ulcers and amputation because of neuropathy.

Tricyclic antidepressants

TCAs include imipramine, amitriptyline, desipramine and nortriptyline. These drugs are effective at decreasing painful symptoms but suffer from multiple side effects that are dosage dependent. One notable side effect is cardiac toxicity, which can lead to fatal arrhythmias. At low dosages used for neuropathy, toxicity is rare, but if symptoms warrant higher doses, complications are more common. Among the TCAs, amitriptyline is most widely used for this condition, but desipramine and nortriptyline have fewer side effects.

Serotonin reuptake inhibitor

SSRIs include fluoxetine, paroxetine, sertraline and citalopram. They are less effective that TCAs in relieving pain, but are better tolerated. Side effects are rarely serious, and do not cause any permanent disabilities. They cause sedation and weight gain, which can worsen a diabetic's glycemic control. They can be used at dosages that also relieve the symptoms of depression, a common concommitent of diabetic neuropathy.

The SSNRI duloxetine (Cymbalta) is approved for diabetic neuropathy. By targeting both serotonin and norepinephrine, it targets the painful symptoms of diabetic neuropathy, and also treats depression if it exists. Typical dosages are between 60mg and 120mg.

Antiepileptic drugs

Antiepileptics (Anti Epileptic Drugs, AED), especially gabapentin and the related pregabalin, are emerging as first line treatment for painful neuropathy. Gabapentin compares favorably with amitriptyline in terms of efficacy, and is clearly safer. Its main side effect is sedation, which does not diminish over time and may in fact worsen. It needs to be taken three times a day, and it sometimes causes weight gain, which can worsen glycemic control in diabetics. Carbamazepine (Tegretol®) is effective but not necessarily safe for diabetic neuropathy. Its first metabolite, oxcarbazepine, is both safe and effective in other neuropathic disorders, but has not been studied in diabetic neuropathy. Topiramate has not been studied in diabetic neuropathy, but has the beneficial side effect of causing mild anorexia and weight loss, and is anecdotally beneficial.

Other treatments

Methylcobalamin, a special form of Vitamin B12, is being studied now for treatment of neuropathy, both injected and oral. Initial studies and anecdotal evidence in cats have been very encouraging. A systematic review of randomized controlled trials suggested benefit, but the trials were not of good quality and the possibility of publication bias exists.

α-lipoic acid, an anti-oxidant that is a non-prescription dietary supplement has shown benefit in a randomized controlled trial that compared once-daily oral doses of 600 mg to 1800 mg compared to placebo, although nausea occurred in the higher doses.

In addition to pharmacological treatment there are several other modalities that help some cases. While lacking double blind trials, these have shown to reduce pain and improve patient quality of life particularly for chronic neuropathic pain: Interferential Stimulation; Acupuncture; Meditation; Cognitive Therapy; and prescribed exercise. In more recent years, Photo Energy Therapy devices are becoming more widely used to treat neuropathic symptoms. Photo Energy Therapy devices emit near infrared light typically at a wavelength of 890nm. This wavelength is is believed to stimulate the release of Nitric Oxide, an Endothelium-derived relaxing factor into the bloodstream, thus vasodilating the capilaries and venuoles in the microcirculatory system. This increase in circulation has been shown effective in various clinical studies to decrease pain and improve sensation in diabetic and non-diabetic patients. Photo Energy Therapy devices seem to address the underlying problem of neuropathies, poor microcirculation, which leads to pain and numbness in the extremities4, 5.

While it is quite true that recognized treatment modalities backed up by double blind trials do not address the underlying causality of diabetic neuropathy, two other programs have had substantial although still anecdotal results. The first involves a program of nutritional supplements put forth in an Internet article researched and published by diabetic neuropathy patients themselves (although heavily referencing peer-reviewed research articles). This article is entitled "A Multidisciplinary Approach to Diabetic Neuropathy Treatment" and its treatment regimen has been instrumental in substantial reversal in individuals throughout the world.

The second method involves a combination of a vegan diet combined with moderate walking exercise. It has been used over several decades to affect both Type II diabetes as well as diabetic peripheral neuropathy.