Most classes of medications that are used to treat painful diabetic neuropathy include drugs that have at best a moderate level of evidence to support their effectiveness or have insufficient evidence to support or refute their use, according to a new guideline published online April 11 in Neurology.
The guideline gives no higher levels of evidence of effectiveness than those in its assessments of studies of vitamins, alpha-lipoic acid, medications absorbed through the skin, and electrical nerve stimulation and other devices. The anticonvulsant drug pregabalin was the only treatment that had strong evidence in support of its effectiveness.
Dr. Vera Bril
Painful diabetic neuropathy affects 16% of the estimated 25 million people with diabetes who live in the United States, yet "many of the patients don’t tell their doctors about their pain, and if they do, they don’t get well treated," lead author Dr. Vera Bril said in an interview in advance of the annual meeting of the American Academy of Neurology, where the guideline was presented.
A wide variety of purported treatments exist for this condition, she added, but "it’s confusing to grasp the entire published literature in this area to know what you should do if you want to use evidence-based medicine. It’s very difficult for an individual physician to judge all of these different papers independently and to determine how good the evidence is. In that way this guideline is a way to give a framework for physicians to use to be able to treat their patients successfully."
Efforts to develop the guideline began in 2007, when experts from the AAN, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation convened to devise a strategy. The following year they began an exhaustive search of the topic in the medical literature, targeting articles that dealt with the treatment of painful diabetic neuropathy, described the intervention clearly, reported the completion rate of the study, and defined the outcome measures clearly. A total of 79 studies met those criteria.
The expert panel then made treatment recommendations based on a review of the articles, and rated each recommendation based on strength of evidence. For example, in the anticonvulsant category, the panel found strong evidence for pregabalin as an agent to reduce pain and improve physical function and quality of life (level A), moderate evidence for gabapentin and sodium valproate (level B), and insufficient evidence to support or refute the use of topiramate (level U).
In the antidepressants category, the panel found moderate evidence to support the use of amitriptyline, venlafaxine, and duloxetine (level B), weak evidence for adding venlafaxine to gabapentin for better response (level C), and insufficient evidence to support or refute the use of desipramine, imipramine, fluoxetine, or the combination of nortriptyline and fluphenazine (level U).
"It’s not just one drug or one approach to consider," emphasized Dr. Bril, professor and chair of neurology at the University of Toronto. "You have to tailor your choice to your patient and his or her clinical status."
In the opioids category, the panel found moderate evidence for the use of dextromethorphan, morphine sulphate, tramadol, and oxycodone (level B). "Opioids should be used carefully," she advised.
The panel found moderate evidence for the use of capsaicin and isosorbide dinitrate spray (level B), weak evidence for the Lidoderm patch (level C), and insufficient evidence to support or refute the usefulness of vitamins andalpha-lipoic acid (level U).
"The fact that we didn’t find evidence in some cases doesn’t mean a treatment won’t work, but that the studies were negative or didn’t show any evidence," Dr. Bril explained.
Moderate evidence was found to support the use of percutaneous electrical nerve stimulation (level B), but the studies were negative for electromagnetic field treatment, low-intensity laser treatment, and Reiki therapy.
Dr. Bril said that this field of medicine is hampered by a lack of rigorous trials. "There’s a lot of work that needs to be done," she said. "A lot of the studies look at pain relief but don’t look at other things that are important, like how the patients function and their quality of life. The studies aren’t long enough. This is a chronic disorder, and the studies here are usually brief. There’s a need for longer-term studies."
The guidelines are also scheduled to appear in the April 2011 edition of Muscle and Nerve as well as the April 2011 edition of PM&R.
Dr. Bril disclosed that she has received research support from Talecris Biotherapeutics, Eisai Inc., Pfizer Inc, Eli Lilly & Co., and Johnson & Johnson. Her 10 coauthors disclosed numerous conflicts of interest with pharmaceutical companies, including travel and speaker honoraria, research support, consulting fees, and advisory board roles.