Evidence-based guideline: Treatment of painful diabetic neuropathy [RETIRED]

Abstract

Objective: To develop a scientifically sound and clinically relevant evidence-based guideline for the treatment of painful diabetic neuropathy (PDN). Methods:We performed a systematic review of the literature from 1960 to August 2008 and classified the studies according to the American Academy of Neurology classification of evidence scheme for a therapeutic article, and recommendations were linked to the strength of the evidence. The basic question asked was: "What is the efficacy of a given treatment (pharmacologic: anticonvulsants, antidepressants, opioids, others; and nonpharmacologic: electrical stimulation, magnetic field treatment, low-intensity laser treatment, Reiki massage, others) to reduce pain and improve physical function and quality of life (QOL) in patients with PDN?" Results and Recommendations:Pregabalin is established as effective and should be offered for relief of PDN (Level A). Venlafaxine, duloxetine, amitriptyline, gabapentin, valproate, opioids (morphine sulfate, tramadol, and oxycodone controlled-release), and capsaicin are probably effective and should be considered for treatment of PDN (Level B). Other treatments have less robust evidence or the evidence is negative. Effective treatments for PDN are available, but many have side effects that limit their usefulness, and few studies have sufficient information on treatment effects on function and QOL. Neurology Diabetic sensorimotor polyneuropathy represents a diffuse symmetric and length-dependent injury to peripheral nerves that has major implications on quality of life (QOL), morbidity, and costs from a public health perspective.1,2 Painful diabetic neuropathy (PDN) affects 16% of patients with diabetes, and it is frequently unreported (12.5%) and more frequently untreated (39%).3 PDN presents an ongoing management problem for patients, caregivers, and physicians. There are many treatment options available, and a rational approach to treating the patient with PDN requires an understanding of the evidence for each intervention.This guideline addresses the efficacy of pharmacologic and nonpharmacologic treatments to reduce pain and improve physical function and QOL in patients with PDN. The pharmacologic agents reviewed include anticonvulsants, antidepressants, opioids, anti-arrhythmics, cannabinoids, aldose reductase inhibitors, protein kinase

Efficacy and Safety of Mirogabalin (DS-5565) for the Treatment of Diabetic Peripheral Neuropathic Pain: A Randomized, Double-Blind, Placebo- and Active Comparator–Controlled, Adaptive Proof-of-Concept Phase 2 Study

“…Beginning at week 1, the highest three mirogabalin dosing groups (15,20, and 30 mg/day) had significantly greater mean reductions from baseline to week 5 in ADPS compared with placebo, and one dosing group (30 mg/day) met the criteria for minimally clinically meaningful effect (i.e., a decrease $1.0 point versus placebo). These data are compelling given the study population had DPNP for a mean of 5.8 years, which is longer than those who participated in pregabalin trials, where subjects were excluded if the duration of DPNP was .5 years (20,(23)(24)(25).…”

“…Overall efficacy and safety data suggest that mirogabalin, given either once or twice daily with or without titration, provides analgesic effects with a potentially wider safety margin compared with current first-line treatments for DPNP. Three of the mirogabalin arms (15,20, and 30 mg/day) had statistically significant reductions in ADPS versus placebo at week 5 and one (30 mg/day) met the criteria of "minimally meaningful effect," defined as a $1.0-point decrease versus placebo. In addition, statistically significant reductions in ADPS versus placebo were observed as early as week 1 in the mirogabalin 15-, 20-, and 30-mg/day groups and continued through week 5 despite a high placebo response rate.…”

“…Nonselective a2d ligands, gabapentin and pregabalin (13), are first-line treatments for DPNP (14,15); however, of these, only pregabalin is approved by the U.S. Food and Drug Administration for treatment of DPNP (14,16). For many patients with DPNP, pain relief is inadequate and therapy is poorly tolerated (4).…”

9. Microvascular Complications and Foot Care

“…Head-tohead treatment comparisons and studies that include quality-of-life outcomes are rare, so treatment decisions must consider each patient's presentation and comorbidities and often follow a trial-and-error approach. Given the range of partially effective treatment options, a tailored and stepwise pharmacological strategy with careful attention to relative symptom improvement, medication adherence, and medication side effects is recommended to achieve pain reduction and improve quality of life (62).…”

9. Microvascular Complications and Foot Care

“…Comparative efficacy studies and trials that include quality-of-life outcomes are rare, so treatment decisions must consider each patient's presentation and comorbidities and often follow a trial-and-error approach. Given the range of partially effective treatment options, a tailored and stepwise pharmacological strategy with careful attention to relative symptom improvement, medication adherence, and medication side effects is recommended to achieve pain reduction and improve quality of life (50,64,65).…”