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.
Objectives: 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.
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 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.
Limitations: We could not include valproate in our analysis owing to the lack of studies reporting
the dichotomous efficacy and safety outcomes.
Conclusion: 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.
Key words: Amitriptyline, diabetic neuropathy, duloxetine, gabapentin, network meta-analysis,
pain, pregabalin, valproate, valproic acid, venlafaxine
Efficacy and Safety of Lacosamide in Painful Diabetic Neuropathy
