The reviewers point to other limitations, including that all studies were short-term, lasting less than 6 months, and that all studies on effective drugs had more than 9% of participants drop out due to adverse effects.
With more than 9% of the United States population having diabetes and an estimated half of those having some form of diabetic peripheral neuropathy, even if symptomless, identifying the optimal treatment is a high priority for neurologists and other clinicians.
Making that especially critical is the fact that, in some cases of severe neuropathy, amputation is the only real option.
New research published online recently in the journal Neurology and in publications of the Agency for Healthcare Research and Quality (AHRQ) suggests that certain antidepressants and antiseizure drugs are among medications that can effectively treat diabetic nerve pain.
“Providing pain relief for neuropathy is crucial to managing this complicated disease,” explained systematic review author Julie Waldfogel, PharmD, of The Johns Hopkins Hospital. “Unfortunately, more research is still needed, as the current treatments have substantial risk of side effects, and few studies have been done on the long-term effects of these drugs.”
Overall, 106 studies were included in the systematic review of trials conducted after release of the American Academy of Neurology’s 2011 guideline “Treatment of Painful Diabetic Neuropathy.”
Moderate-strength evidence suggested that duloxetine and venlafaxine, which act as serotonin-norepinephrine reuptake inhibitors, were effective in reducing neuropathy-related pain. Only weak evidence was identified, however, for the effectiveness of the botulinum toxin, the antiseizure drugs pregabalin and oxcarbazepine, tricyclic antidepressants, and atypical opioids.
Waldfogel emphasized that the long-term use of opioids is not recommended for chronic neuropathic pain, adding that the guidance was bolstered by the lack of evidence of long-term benefit, as well as growing concerns about the risk of abuse, misuse, and overdose.
Overall, the reviewers said, “For reducing pain, duloxetine and venlafaxine, pregabalin and oxcarbazepine, tricyclic antidepressants, atypical opioids, and botulinum toxin were more effective than placebo.”
Some of the evidence was contrary to the 2011 AAN guideline, however. For example, researchers note that pregabalin works in the same way as gabapentin, which was found to be no more effective than placebo in the recent review. The previous guideline said the drug was probably effective.
In addition, the seizure drug valproate and topical capsaicin cream, which were recommended as probably effective in the 2011 AAN guideline, were deemed ineffective in this meta-analysis.
“Unfortunately, there was not enough evidence available to determine if these treatments had an impact on quality of life,” Waldfogel said. “Future studies are needed to assess this.”