New ways to manage diabetic neuropathy

Statistics show that at least one-half of all people with diabetes have diabetic peripheral neuropathy (DPN). And while many of these patients may develop a lack of sensation, approximately 11% have chronic and painful symptoms that seriously affect their quality of life. For this reason, and the current lack of consensus about the condition's pathophysiology and most effective treatment, a group of 11 pain specialists convened in a two-day conference in 2005 to create the first diabetic peripheral neuropathic pain (DPNP) guidelines.

"The pathophysiology of DPNP is very complex, and there hasn't been one defined mechanism to date," said Stephen M. Setter, Pharm.D., CDE, DVM, associate professor of pharmacotherapy at Washington State University in Spokane. "Decades of research elucidating the pathophysiology of DPNP have failed thus far to produce a treatment that prevents or reverses its development or progression." Setter believes that oxidative stress, the formation of advanced glycation end products, protein kinase C, and the polyol pathway are all involved. Because the clinical situation is just as complex, with few effective therapies, "guidelines were critically needed to aid the practitioner in making rational medication choices," he said.

Using data from clinical trials, the group of pain experts weighed the evidence available for medications used to treat DPNP and categorized the drugs into one of three categories (see table). First-tiered choices had two or more randomized controlled trials that showed their effectiveness in treating DPN, and second-tiered drugs were shown effective in one trial for DPN and one or more trials of other painful neuropathies. The final category, honorable mention, includes topical therapies and other drugs that have shown effectiveness versus other painful neuropathies in one or more trials.

When patients do not respond adequately to the first-tiered agents, or if adverse events are too severe, a patient may require a change to another first-tiered drug with a different mechanism of action. Another option is to switch to a second-tiered agent with a different mechanism of action than that of the previously used drug. The third choice is to add another first-or second-line drug to the initial one. In this case, the guidelines suggest using principles of rational polypharmacy, including consideration of possible therapeutic synergies between drugs, choosing drugs with complementary mechanisms of action, and avoiding choices with potential additive adverse effects. Unfortunately, the pain specialists who drafted the new recommendations said that in spite of these options, very few patients would achieve 100% pain relief.

The Consensus Guidelines: Assessment, Diagnosis, and Treatment of Diabetic Peripheral Neuropathic Pain were published in an April 2006 supplement to the Mayo Clinic Proceedings. They are available on-line at http://www.paineducators.org/.