title: Capsaicin 8% Patch Versus Oral Neuropathic Pain Medications for the Treatment of Painful Diabetic Peripheral Neuropathy: A Systematic Literature Review and Network Meta-analysis.
abstract: OBJECTIVE
  A network meta-analysis (NMA) was performed, aiming to assess the relative efficacy and tolerability of the capsaicin 179-mg (8% weight for weight) cutaneous patch (capsaicin 8% patch) compared with oral, centrally acting agents (ie, pregabalin, gabapentin, duloxetine, amitriptyline) in patients with painful diabetic peripheral neuropathy (PDPN).
  
  
  METHODS
  A systematic search of EMBASE/MEDLINE, Cochrane Library, and the National Health Service Centre for Reviews and Dissemination Database of Abstracts of Reviews of Effects was conducted to identify all randomized controlled trials. Data from eligible studies according to predefined inclusion and exclusion criteria were extracted, and analyses were based on aggregate-level data. Efficacy outcomes were the proportions of patients with ≥30% and ≥50% reductions in pain, and tolerability outcomes were somnolence, dizziness, nausea, diarrhea, constipation, headache, fatigue, insomnia, and rate of discontinuation due to adverse events (AEs). Data were analyzed by using a Bayesian NMA. Fixed and random effects models were estimated. Relative treatment effect was presented as odds ratios (ORs) with 95% CIs. Sources of heterogeneity were assessed.
  
  
  RESULTS
  The NMA included 25 randomized controlled trials. For ≥30% pain reduction, the capsaicin 8% patch was significantly more effective than placebo (OR, 2.28 [95% CI, 1.19-4.03]), exhibited a numerical advantage compared with pregabalin (OR, 1.83 [95% CI, 0.91-3.34]) and gabapentin (OR, 1.66 [95% CI, 0.74-3.23]), and had similar efficacy compared with duloxetine (OR, 0.99 [95% CI, 0.5-1.79]). The evidence available was not sufficient to assess the relative efficacy of amitriptyline. In the NMA for tolerability, the capsaicin 8% patch was only included for headache because the incidence was 0% for the other outcomes. Oral, centrally acting agents had a significantly elevated risk compared with placebo for somnolence (pregabalin, gabapentin, duloxetine, and amitriptyline), dizziness (pregabalin, gabapentin, duloxetine, and amitriptyline), nausea (duloxetine), diarrhea (duloxetine), fatigue (duloxetine), and discontinuation because of AEs (pregabalin, gabapentin, and duloxetine). Compared with pregabalin and gabapentin, duloxetine had a significantly lower risk of dizziness but a significantly higher risk of nausea.
  
  
  CONCLUSIONS
  This NMA suggests that the efficacy observed with the capsaicin 8% patch is similar to that observed with oral agents (ie, pregabalin, duloxetine, gabapentin) in patients with PDPN. The oral agents were associated with a significantly elevated risk of somnolence, dizziness, fatigue, and discontinuation because of AEs compared with placebo. The capsaicin 8% patch was as effective as oral centrally acting agents in these patients with PDPN but offers systemic tolerability benefits.
authors.affiliation: Astellas Pharma Europe BV, Medical Affairs, Leiden, The Netherlands. Electronic address: floortjevannooten@hotmail.com.
authors.forename: Floortje
authors.initials: F
authors.lastname: van Nooten
authors.affiliation: Pharmerit International, Rotterdam, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Treur
authors.affiliation: Pharmerit International, Rotterdam, The Netherlands.
authors.forename: Krystallia
authors.initials: K
authors.lastname: Pantiri
authors.affiliation: Astellas Pharma Europe BV, Medical Affairs, Leiden, The Netherlands.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Stoker
authors.affiliation: Pharmerit International, Rotterdam, The Netherlands.
authors.forename: Mata
authors.initials: M
authors.lastname: Charokopou
mesh_terms: D000284:Administration, Oral; D000700:Analgesics / Q000008:administration & dosage / Q000627:therapeutic use*; D002211:Capsaicin / Q000008:administration & dosage / Q000627:therapeutic use*; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D006801:Humans; D009437:Neuralgia / Q000188:drug therapy*; D057968:Transdermal Patch
chemical_list: D000700:Analgesics; D002211:Capsaicin
keywords: capsaicin patch; duloxetine; gabapentin; network meta-analysis; painful diabetic peripheral neuropathy; pregabalin