HONOLULU—A new evidence-based guideline regarding the pharmacologic and nonpharmacologic treatment of painful diabetic neuropathy (PDN) was presented at the 63rd Annual Meeting of the American Academy of Neurology (AAN).
The guideline, prepared by the AAN in collaboration with the American Association of Neuromuscular and Electrodiagnostic Medicine and the American Academy of Physical Medicine and Rehabilitation, reports strong evidence for the use of pregabalin in patients with PDN, if clinically appropriate. Venlafaxine, duloxetine, amitriptyline, gabapentin, valproate, opioids, and capsaicin, as well as percutaneous electrical nerve stimulation, are “probably effective” and therefore should be considered as treatment, according to the recommendations, which were also published in the April 11 online Neurology and in the April issues of Muscle and Nerve and Physical Medicine and Rehabilitation.
“This is a major problem for patients with diabetes,” said lead author Vera Bril, MD, Professor of Neurology at the University of Toronto. “As many as 16% of them have PDN, and many of them don’t have proper treatment. As we emphasize the use of evidence-based guidelines to treat different disorders, it becomes clear that this field is very confusing, because of the volume of literature. So the guideline has been developed and will provide a framework for physicians to use when they are treating their patients.”
A Systematic Review
Dr. Bril and colleagues conducted a systematic review of literature from 1960 to August 2008 and grouped the studies according to the AAN’s classification of evidence scheme for a therapeutic article. The investigators sought to determine the efficacy of a given treatment—either pharmacologic (anticonvulsants, antidepressants, opioids, and other agents) or nonpharmacologic (electrical stimulation, magnetic field treatment, low-intensity laser treatment, Reiki massage, or others)—in reducing pain and improving physical function and quality of life in patients with PDN.
The researchers identified 2,234 citations, which resulted in 463 articles; 79 were viewed as relevant and then were rated by at least two authors. The strength of practice recommendations were linked directly to the levels of evidence and rated as follows—A (established as effective); B (probably effective, ineffective, or harmful); C (possibly effective, ineffective, or harmful); or U (data inadequate or conflicting). “This process was a very large-scale, peer-reviewed activity, with a lot of input from many physicians expert in the field,” said Dr. Bril.
The study panel used the following outcome measures, listed in order of preference—the difference in the proportion of patients reporting a greater than 30% to 50% change from baseline on a Likert or visual analog pain scale compared with no treatment or comparative treatment; percent change from baseline on a Likert or visual analog pain scale compared with no treatment or comparative treatment; and any other quantitative measure of pain reduction provided by the investigators.
Anticonvulsants, Antidepressants, and Opioids
After analyzing the data regarding anticonvulsants, the guideline authors recommended that, if clinically appropriate, pregabalin should be offered for the treatment for PDN (Level A), and that gabapentin and sodium valproate should be considered as treatment (Level B). “There is insufficient evidence to support or refute the use of topiramate for the treatment of PDN,” advised Dr. Bril and colleagues. “Oxcarbazepine, lamotrigine, and lacosamide should probably not be considered for the treatment of PDN.”
Furthermore, the researchers noted that although sodium valproate may be effective, “it is potentially teratogenic and should be avoided in diabetic women of childbearing age … Due to potential adverse effects such as weight gain and potential worsening of glycemic control, this drug is unlikely to be the first treatment choice for PDN.”
Among antidepressants, the guideline recommends that amitriptyline, venlafaxine, and duloxetine should be considered for the treatment of PDN (Level B), and that the data are insufficient to recommend one of these agents over the other. The authors also noted that venlafaxine may be added to gabapentin for a better response (Level C). “There is insufficient evidence to support or refute the use of desipramine, imipramine, fluoxetine, or the combination of nortriptyline and fluphenazine in the treatment of PDN (Level U),” they stated.
Regarding the use of opioids, the investigators recommend that dextromethorphan, morphine sulfate, tramadol, and oxycodone should be considered for the treatment of PDN (Level B) and that the research is insufficient to recommend one drug versus the other. However, the authors urged caution concerning the use of opioids. “Both tramadol and dextromethorphan were associated with substantial adverse events (eg, sedation in 18% on tramadol and 58% on dextromethorphan, nausea in 23% on tramadol, and constipation in 21% on tramadol),” they reported. “The use of opioids can be associated with the development of novel pain syndromes such as rebound headache. Chronic use of opioids leads to tolerance and frequent escalation of dose.”