New evidence-based guidelines for PDN treatment

In an effort to address the efficacy of various treatment options available to reduce pain and improve physical function and quality of life (QOL) in patients with painful diabetic neuropathy (PDN), a broad literature review was conducted and new guidelines were published online May 17 in Neurology and presented at the American Academy of Neurology Annual Meeting in Honolulu.

The literature review was conducted using MEDLINE and EMBASE from 1960 to August 2008. Of the 2,234 citations identified, 79 were included in the analysis. The studies were classified according to the American Academy of Neurology classification of evidence scheme for a therapeutic article and treatments were classified as Level A (established as effective, ineffective, or harmful), Level B (probably effective, ineffective, or harmful), Level C (possibly effective, ineffective, or harmful), and Level U (data inadequate or conflicting). Recommendations were linked to the strength of the evidence.

The pharmacologic agents reviewed included anticonvulsants, antidepressants, opioids, anti-arrhythmics, cannabinoids, aldose reductase inhibitors, protein kinase C beta inhibitors, antioxidants (alpha-lipoic acid), transketolase activators (thiamines and allithiamines), topical medications (analgesic patches, anesthetic patches, capsaicin cream, clonidine), and others. The nonpharmacologic modalities included infrared therapy, shoe magnets, exercise, acupuncture, external stimulation (transcutaneous electrical nerve stimulation), spinal cord stimulation, biofeedback and behavioral therapy, surgical decompression, and intrathecal baclofen.

Summary of treatment recommendations

The Level A recommendation is that pregabalin 300 mg/d to 600 mg/d is established as effective in lessening the pain of PDN and should be prescribed for relief, if clinically appropriate. It also improves QOL and lessens sleep interference.

The Level B recommendations included:

• Gabapentin 900 mg/d to 3,600 mg/d and sodium valproate 500 mg/d to1,200 mg/d may be effective and should be considered; however the authors note that sodium valproate is potentially teratogenic and may not be appropriate for diabetic women of childbearing age.

• Venlafaxine 75 mg/d to 225 mg/d, duloxetine 60 mg/d to 120 mg/d, amitriptyline 25 mg/d to 100 mg/d, dextromethorphan 400 mg/d, morphine sulphate titrated to 120 mg/d, tramadol 210 mg/d, oxycodone mean 37 mg/d, max 120 mg/d should be considered for treatment; however in each drug class, data were insufficient for researchers to recommend 1 agent over another.

Capsaicin 0.075% 4 times daily and isosorbide dinitrate spray should be considered for treatment.

Percutaneous electrical nerve stimulation 3 to 4 weeks should be considered for the treatment of PDN.

Treatments not recommended include oxcarbazepine, lamotrigine, lacosamide, clonidine, pentoxifylline, mexiletine, magnetic field treatment, low-intensity laser therapy, and Reiki therapy.

Other treatments were associated with weak or insufficient evidence, so researchers could not make a recommendation.

“The panel recognizes that PDN is a chronic disease and that there are no data on the efficacy of the chronic use of any treatment, as most trials have durations of 2–20 weeks. It is important to note that the evidence is limited, the degree of effectiveness can be minor, the side effects can be intolerable, the impact on improving physical function is limited, and the cost is high, particularly for novel agents,” the authors concluded.