Pharmacologic Interventions for Painful Diabetic Neuropathy

This article has been corrected. The original version (PDF) is appended to this article as a Supplement. Background: Multiple treatments for painful diabetic peripheral neuropathy are available. Purpose: To evaluate the comparative effectiveness of oral and topical analgesics for diabetic neuropathy. Data Sources: Multiple electronic databases between January 2007 and April 2014, without language restriction. Study Selection: Parallel or crossover randomized, controlled trials that evaluated pharmacologic treatments for adults with painful diabetic peripheral neuropathy. Data Extraction: Duplicate extraction of study data and assessment of risk of bias. Data Synthesis: 65 randomized, controlled trials involving 12 632 patients evaluated 27 pharmacologic interventions. Approximately one half of these studies had high or unclear risk of bias. Nine head-to-head trials showed greater pain reduction associated with serotonin–norepinephrine reuptake inhibitors (SNRIs) than anticonvulsants (standardized mean difference [SMD], −0.34 [95% credible interval {CrI}, −0.63 to −0.05]) and with tricyclic antidepressants (TCAs) than topical capsaicin 0.075%. Network meta-analysis showed that SNRIs (SMD, −1.36 [CrI, −1.77 to −0.95]), topical capsaicin (SMD, −0.91 [CrI, −1.18 to −0.08]), TCAs (SMD, −0.78 [CrI, −1.24 to −0.33]), and anticonvulsants (SMD, −0.67 [CrI, −0.97 to −0.37]) were better than placebo for short-term pain control. Specifically, carbamazepine (SMD, −1.57 [CrI, −2.83 to −0.31]), pregabalin (SMD, −0.55 [CrI, −0.94 to −0.15]), venlafaxine (SMD, −1.53 [CrI, −2.41 to −0.65]), duloxetine (SMD, −1.33 [CrI, −1.82 to −0.86]), and amitriptyline (SMD, −0.72 [CrI, −1.35 to −0.08]) were more effective than placebo. Adverse effects included somnolence and dizziness with TCAs, SNRIs, and anticonvulsants; xerostomia with TCAs; and peripheral edema and burning sensation with pregabalin and capsaicin. Limitation: Confidence in findings was limited because most evidence came from indirect comparisons of trials with short (≤3 months) follow-up and unclear or high risk of bias. Conclusion: Several medications may be effective for short-term management of painful diabetic neuropathy, although their comparative effectiveness is unclear. Primary Funding Source: Mayo Foundation for Medical Education and Research.