Open AccessComparative Efficacy and Safety of Six Antidepressants and Anticonvulsants in Painful Diabetic Neuropathy: A Network Meta-analysis
Author(s) -
Neelima Rudroju,
Dipika Bansal,
Shiva Teja Talakokkula,
Kapil Gudala,
Debasish Hota,
Anil Bhansali,
Babita Ghai
Publication year - 2013
Publication title -
pain physician
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 99
eISSN - 2150-1149
pISSN - 1533-3159
DOI - 10.36076/ppj.2013/16/e705
Subject(s) - medicine , meta analysis , diabetic neuropathy , medline , anesthesia , intensive care medicine , diabetes mellitus , political science , law , endocrinology
Background: Anticonvulsants and antidepressants are mostly used in management of painfuldiabetic neuropathy (PDN). However there are few direct comparisons between drugs of theseclasses, making evidence-based decision-making in the treatment of painful diabetic neuropathydifficult.Objectives: This study aimed to perform a network meta-analysis and benefit-risk analysis toevaluate the comparative efficacy and safety of these drugs in PDN treatment.Study Design: Comparative effectiveness study.Setting: Medical Education and Research facility in India.Methods: A comprehensive data search was done in PubMed, Cochrane, and Embase upto August 2012. We then systematically reviewed the studies which compared any of 6 drugsfor the management of PDN: amitriptyline, duloxetine, gabapentin, pregabalin, valproate, andvenlafaxine or any of their combinations. We performed a random-effects network meta-analysisto 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 primaryoutcomes for efficacy and safety, respectively. We also performed benefit-risk analysis, takingefficacy 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 thangabapentin. 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, andamitriptyline. Benefit-risk balance favored the order: gabapentin, venlafaxine, pregabalin,duloxetine/gabapentin combination, duloxetine, placebo, and amitriptyline.Limitations: We could not include valproate in our analysis owing to the lack of studies reportingthe dichotomous efficacy and safety outcomes.Conclusion: Gabapentin was found to be most efficacious and amitriptyline to be least safeamong the treatments included in the study. Gabapentin showed most favorable balance betweenefficacy and safety.Key words: Amitriptyline, diabetic neuropathy, duloxetine, gabapentin, network meta-analysis,pain, pregabalin, valproate, valproic acid, venlafaxine