Pharmacotherapy of neuropathic pain: Efficacy of first-line drugs

Abstract

Neuropathic pain often requires long-term treatment, but response to pharmacotherapy is limited and individually variable. The aim was to compare the efficacy and therapeutic position of first-line medicines for neuropathic pain in adults. A targeted narrative literature review was conducted by searching PubMed/MEDLINE and the Cochrane Library for publications from January 2015 to July 2026. Search terms were "neuropathic pain", "pharmacotherapy", "tricyclic antidepressants", "serotonin-norepinephrine reuptake inhibitors", "gabapentin", "pregabalin", and "head-to-head trial". Guidelines, systematic reviews, and meta-analyses evaluating pain-intensity reduction in adults were included; trigeminal neuralgia and sciatica were excluded because they require separate treatment algorithms. The most consistent first-line recommendations concern tricyclic antidepressants, serotonin and norepinephrine reuptake inhibitors, gabapentin, and pregabalin. In a meta-analysis of 229 studies, the number needed to treat (NNT) for one patient to achieve at least 50% pain reduction was 3.6 for tricyclic antidepressants, 6.4 for serotonin and norepinephrine reuptake inhibitors, 6.3 for gabapentin, and 7.7 for pregabalin. However, a meta-analysis of 10 direct-comparison studies involving 920 participants found no clinically relevant difference between tricyclic antidepressants and gabapentin or pregabalin (mean difference 0.10; 95% confidence interval -0.13 to 0.32). Gabapentin and pregabalin bind to the α2δ subunit of voltage-gated calcium channels and do not inhibit sodium channels. The findings indicate that no drug class is universally the most effective. Treatment selection should be individualized according to comorbidities, age, renal function, adverse-effect profile, and previous treatment response.