Medical Sciences
Comparative Effectiveness of Tricyclic Antidepressants, Serotonin–Norepinephrine Reuptake Inhibitors, and Anticonvulsants for Diabetic Painful Neuropathy: A Systematic Review and Meta-Analysis
By Sreeya Reddy, Shakeel Ahmed and Munmun Chattopadhyay.
Abstract
Introduction
Diabetic painful neuropathy (DPN) is one of the most common and debilitating complications of diabetes, substantially impairing the quality of life of patients. In the absence of disease-modifying therapies, treatment remains focused on symptomatic pain control with non-opioid pharmacologic agents; however, comparative evidence guiding optimal medication selection remains limited. Using a systematic review, pairwise meta-analysis, and network meta-analysis, this study compares the effectiveness of current non-opioid-based treatments, including amitriptyline, duloxetine, gabapentin, and pregabalin, for pain reduction in patients with DPN.
Methods
PubMed and Google Scholar were systematically searched for randomized and clinical trials published between 2010 and 2025 evaluating these medications as monotherapy for DPN. A total of n = 11 studies met the inclusion criteria. Pain outcomes measured using the Numeric Rating Scale (NRS), Visual Analog Scale (VAS), or Brief Pain Inventory (BPI) were standardized to a common metric. Random-effects pairwise meta-analyses were performed to estimate within-drug treatment effects, followed by a frequentist network meta-analysis to compare therapies through direct and indirect evidence. Mean change in pain severity was the primary outcome. We performed heterogeneity, network consistency, and sensitivity analyses under varying correlation assumptions.