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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.