title: Pharmacologic interventions for painful diabetic neuropathy: An umbrella systematic review and comparative effectiveness network meta-analysis.
abstract: BACKGROUND
  Multiple treatments for painful diabetic peripheral neuropathy are available.
  
  
  OBJECTIVE
  To evaluate the comparative effectiveness of oral and topical analgesics for diabetic neuropathy.
  
  
  METHODS
  Multiple electronic databases between January 2007 and April 2014, without language restriction.
  
  
  METHODS
  Parallel or crossover randomized, controlled trials that evaluated pharmacologic treatments for adults with painful diabetic peripheral neuropathy.
  
  
  METHODS
  Duplicate extraction of study data and assessment of risk of bias.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  Several medications may be effective for short-term management of painful diabetic neuropathy, although their comparative effectiveness is unclear.
  
  
  BACKGROUND
  Mayo Foundation for Medical Education and Research.
authors.forename: Marcio L
authors.initials: ML
authors.lastname: Griebeler
authors.forename: Oscar L
authors.initials: OL
authors.lastname: Morey-Vargas
authors.forename: Juan P
authors.initials: JP
authors.lastname: Brito
authors.forename: Apostolos
authors.initials: A
authors.lastname: Tsapas
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Barbara G
authors.initials: BG
authors.lastname: Carranza Leon
authors.forename: Olivia J
authors.initials: OJ
authors.lastname: Phung
authors.forename: Victor M
authors.initials: VM
authors.lastname: Montori
authors.forename: M Hassan
authors.initials: MH
authors.lastname: Murad
mesh_terms: D000701:Analgesics, Opioid / Q000627:therapeutic use; D000927:Anticonvulsants / Q000009:adverse effects / Q000627:therapeutic use*; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects / Q000627:therapeutic use*; D015982:Bias; D002211:Capsaicin / Q000009:adverse effects / Q000627:therapeutic use*; D003929:Diabetic Neuropathies / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D010146:Pain / Q000188:drug therapy* / Q000209:etiology; D016032:Randomized Controlled Trials as Topic; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D000701:Analgesics, Opioid; D000927:Anticonvulsants; D000929:Antidepressive Agents, Tricyclic; D002211:Capsaicin; D017367:Selective Serotonin Reuptake Inhibitors