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A new guideline from the American Academy of Neurology addresses treatment of patients with painful diabetic neuropathy. Based on a comprehensive literature review, the authors conclude that only one drug, the anticonvulsant pregabalin (Lyrica), merits “Level A” support (i.e., support based on at least 2 high-quality randomized trials). However, the highest-quality pregabalin trials demonstrated only small benefits over placebo (effect sizes of 10%–15%). Numerous drugs — particularly antidepressants, other anticonvulsants, and opioids — have “Level B” (i.e., less rigorous) ratings; effect sizes were larger for some of these drugs than for pregabalin, but studies were methodologically inferior.
The guideline authors call for head-to-head drug comparisons, and one has just been published. In a double-blind, randomized, crossover trial, researchers compared 6-week courses of amitriptyline and duloxetine (Cymbalta) in 58 adults with painful diabetic neuropathy. Amitriptyline was titrated from 10 to 50 mg (if tolerated), and duloxetine was titrated from 20 to 60 mg. Pain relief provided by the two drugs was similar; for example, with both drugs, 60% of patients improved by >30% on visual analog pain scales. Dry mouth was more common with amitriptyline, constipation was more common with duloxetine, and somnolence was common with both.
Bril V et al. Evidence-based guideline: Treatment of painful diabetic neuropathy. Report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology 2011 Apr 11; [e-pub ahead of print]. (http://dx.doi.org/10.1212/WNL.0b013e3182166ebe)
Kaur H et al. A comparative evaluation of amitriptyline and duloxetine in painful diabetic neuropathy: A randomized, double-blind, cross-over clinical trial. Diabetes Care 2011 Apr; 34:818. (http://dx.doi.org/10.2337/dc10-1793)
Comment
This guideline reminds us that more effective and better-tolerated therapies are needed for painful diabetic neuropathy. The only FDA-approved treatments are pregabalin and duloxetine; other drugs are prescribed off-label. The guideline lists pregabalin as the only Level A treatment, but that's partly because large industry-sponsored studies exist for brand-name pregabalin but not for many of the other drugs. For cost reasons, many patients will prefer initial trials of inexpensive generic amitriptyline and gabapentin, rather than expensive brand-name drugs (duloxetine and pregabalin).