Analysis finds several treatments for painful diabetic neuropathy more effective than placebo

A large meta-analysis recently compared the effectiveness of pharmacological treatments for painful diabetic neuropathy.

Researchers included 65 randomized, controlled trials of oral and topical analgesics, published between January 2007 and April 2014. More than 12,000 patients with painful diabetic peripheral neuropathy and 27 interventions were included. Results were published in the Nov. 4 Annals of Internal Medicine.

Using the 9 head-to-head trials available, analysis authors concluded that serotonin-norepinephrine reuptake inhibitors (SNRIs) reduced pain more than anticonvulsants and that tricyclic antidepressants (TCAs) reduced pain more than topical capsaicin 0.075%. There wasn't enough evidence to make any other direct comparisons, but the network meta-analysis showed that SNRIs, topical capsaicin, TCAs, and anticonvulsants (specifically, carbamazepine, venlafaxine, duloxetine, and amitriptyline) were all better than placebo.

As for adverse effects, patients taking TCAs, SNRIs, and anticonvulsants frequently reported somnolence and dizziness. Xerostomia was common with TCAs, and nausea, constipation, and dyspepsia were common with SNRIs. Peripheral edema was reported with pregabalin and burning at the application site was reported with capsaicin.

While the results of this analysis add to the body of evidence on treatments for diabetic neuropathy, it's still unclear which are most effective, the authors concluded. They noted that their research was limited by the lack of head-to-head trials, the heterogeneity of results, high risk of bias, and little data going beyond 3 months of treatment. Only duloxetine and pregabalin are currently FDA approved for neuropathic pain in diabetes, and the American Academy of Neurology currently recommends pregabalin as the first-line treatment, the authors noted.

That recommendation is based on a “somewhat arbitrary cutoff,” according to an accompanying editorial. Physicians should base their choice among the effective therapies on cost, comorbid conditions, and potential adverse effects, the editorialists recommended. Gabapentin, amitriptyline, nortriptyline, and capsaicin are dramatically less expensive than pregabalin, duloxetine, and venlafaxine. The editorialists called for more comparative effectiveness trials but concluded that currently “the most cost-effective approach is to try 1 or more TCAs as first-line medications, followed by gabapentin.”