title: Comparative efficacy and safety of six antidepressants and anticonvulsants in painful diabetic neuropathy: a network meta-analysis.
abstract: BACKGROUND
  Anticonvulsants and antidepressants are mostly used in management of painful diabetic neuropathy (PDN). However there are few direct comparisons between drugs of these classes, making evidence-based decision-making in the treatment of painful diabetic neuropathy difficult.
  
  
  OBJECTIVE
  This study aimed to perform a network meta-analysis and benefit-risk analysis to evaluate the comparative efficacy and safety of these drugs in PDN treatment.
  
  
  METHODS
  Comparative effectiveness study.
  
  
  METHODS
  Medical Education and Research facility in India.
  
  
  METHODS
  A comprehensive data search was done in PubMed, Cochrane, and Embase up to August 2012. We then systematically reviewed the studies which compared any of 6 drugs for the management of PDN: amitriptyline, duloxetine, gabapentin, pregabalin, valproate, and venlafaxine or any of their combinations. We performed a random-effects network meta-analysis to rank treatments in terms of efficacy and safety. We chose the number of patients experiencing = 50% reduction in pain and number of patient withdrawals due to adverse events (AE) as primary outcomes for efficacy and safety, respectively. We also performed benefit-risk analysis, taking efficacy outcome as benefit and safety outcome as risk. Analysis was intention-to-treat.
  
  
  RESULTS
  We included 21 published trials in the analysis. Duloxetine, gabapentin, pregabalin, and venlafaxine were shown to be significantly efficacious compared to placebo with odds ratios (OR) of 2.12, 3.98, 2.78, and 4.43, respectively. Amitriptyline (OR: 7.03, 95% confidence interval [CI]: 1.87, 29.05) and duloxetine (OR: 3.26, 95% CI: 1.04, 9.97) caused more withdrawals than gabapentin. The ranking order of efficacy was gabapentin, venlafaxine, pregabalin, duloxetine/gabapentin, duloxetine, amitriptyline, and placebo and the ranking order of safety was placebo, gabapentin, pregabalin, venlafaxine, duloxetine/gabapentin combination, duloxetine, and amitriptyline. Benefit-risk balance favored the order: gabapentin, venlafaxine, pregabalin, duloxetine/gabapentin combination, duloxetine, placebo, and amitriptyline.
  
  
  CONCLUSIONS
  We could not include valproate in our analysis owing to the lack of studies reporting the dichotomous efficacy and safety outcomes.
  
  
  CONCLUSIONS
  Gabapentin was found to be most efficacious and amitriptyline to be least safe among the treatments included in the study. Gabapentin showed most favorable balance between efficacy and safety.
authors.affiliation: Clinical Research Unit, Department of Pharmacy Practice, National Institute of Pharmaceutical Education and Research, SAS Nagar (Mohali), India; Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Neelima
authors.initials: N
authors.lastname: Rudroju
authors.forename: Dipika
authors.initials: D
authors.lastname: Bansal
authors.forename: Shiva Teja
authors.initials: ST
authors.lastname: Talakokkula
authors.forename: Kapil
authors.initials: K
authors.lastname: Gudala
authors.forename: Debasish
authors.initials: D
authors.lastname: Hota
authors.forename: Anil
authors.initials: A
authors.lastname: Bhansali
authors.forename: Babita
authors.initials: B
authors.lastname: Ghai
mesh_terms: D000588:Amines / Q000627:therapeutic use; D000639:Amitriptyline / Q000627:therapeutic use; D000927:Anticonvulsants / Q000627:therapeutic use*; D000928:Antidepressive Agents / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003509:Cyclohexanecarboxylic Acids / Q000627:therapeutic use; D003511:Cyclohexanols / Q000627:therapeutic use; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D000068736:Duloxetine Hydrochloride; D000077206:Gabapentin; D006801:Humans; D000069583:Pregabalin; D013876:Thiophenes / Q000627:therapeutic use; D014635:Valproic Acid / Q000627:therapeutic use; D000069470:Venlafaxine Hydrochloride; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000588:Amines; D000927:Anticonvulsants; D000928:Antidepressive Agents; D003509:Cyclohexanecarboxylic Acids; D003511:Cyclohexanols; D013876:Thiophenes; D000639:Amitriptyline; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D000077206:Gabapentin; D000069470:Venlafaxine Hydrochloride; D000068736:Duloxetine Hydrochloride