Long-Term Efficacy and Safety of Treatments for Chronic Peripheral Neuropathic Pain: A Systematic Review and Narrative Synthesis

Peripheral neuropathic pain (PNP) is a chronic condition that often requires long-term treatment. In 2025, the Neuropathic Pain Special Interest Group (NeuPSIG) updated its recommendations for treatment of neuropathic pain based on data from double-blind, randomized controlled trials (RCTs) with a duration of ≥ 3 weeks. To complement the existing body of evidence, we reviewed the long-term efficacy/safety of NeuPSIG-recommended treatments for PNP. We conducted a systematic literature review including clinical trials and observational studies of any design. Two literature searches were performed using PubMed and Embase (December 2024, May 2025). We included studies that enrolled ≥ 50 adult patients with PNP receiving ≥ 1 treatment recommended in the 2025 NeuPSIG guidance and with duration of ≥ 13 weeks. A supplemental search for long-term studies on high-concentration capsaicin 8% patch (HCCP) was performed. Results were synthesized narratively due to heterogeneity in study designs and outcomes. We included 34 articles in our analysis (31 studies) varying in design, including interventional (RCTs and open-label studies) and observational studies. Most studies had a duration of 26–52 weeks. Four treatments (HCCP, duloxetine, gabapentin, pregabalin) were evaluated in ≥ 5 studies. HCCP was evaluated in the greatest number of long-term studies ( n = 13) and in various PNP conditions, followed by duloxetine ( n = 7) in painful diabetic peripheral neuropathy (pDPN) only, gabapentin ( n = 6) in various PNP conditions and pregabalin ( n = 5) mostly in pDPN. Collected data support long-term efficacy of all products. The lowest rates of discontinuations due to adverse events were reported with HCCP. The findings from this literature review emphasize the importance of expanding long-term evidence for chronic pain therapies. The review determined that the largest body of evidence is available for HCCP. Finally, it highlights the need for more standardized long-term evidence studies for chronic pain therapies.