Pharmacologic interventions for painful diabetic neuropathy: an umbrella systematic review and comparative effectiveness network meta-analysis (Protocol)

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]), 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.