Updated Guidelines Needed for Neuropathic Pain Therapies

New research supports a revision of the Neuropathic Pain Special Interest Group (NeuPSIG) recommendations for treating neuropathic pain as uncertainty remains with current treatment options.1,2

“Neuropathic pain, caused by a lesion or disease of the somatosensory nervous system, substantially affects patients’ quality of life and imposes a substantial economic burden on individuals and society. Regardless of the etiology of nerve damage, the treatment of neuropathic pain is challenging, requiring accurate diagnosis and biopsychosocial assessment and the application of evidence-based recommendations that consider efficacy and safety of available treatments,” lead investigator Nadia Soliman, PhD, Pain Research Group, Department of Surgery and Cancer, Imperial College London, London, United Kingdom, and colleagues wrote.1

Soliman and colleagues included 284 pharmacological and 29 neuromodulation double-blind, randomized, placebo-controlled studies, for a total of 313 studies, in the meta-analysis, from Embase, PubMed, the International Clinical Trials Registry, and ClinicalTrials.gov with data from 2013 to 2024. A total of 48,789 adult participants (20,611 female and 25,078 male) were included in the studies to be randomized to trial groups.1

The study’s primary efficacy outcome was the proportion of responders (50% or 30% reduction in baseline pain intensity or moderate pain relief) and the primary safety outcome was the number of participants who withdrew from the treatment due to adverse events. They also calculated a risk difference, to calculate the number needed to treat (NNT) and the number needed to harm (NNH) for each treatment, for each comparison and did a random-effects meta-analysis. Soliman and colleagues used the Cochrane risk of bias tool 2 to assess risk of bias and GRADE to assess certainty of evidence. They then compiled recommendations based on evidence of efficacy, adverse events, accessibility, and cost, and feedback from engaged lived experience partners.

Overall, the investigators found evidence for a strong recommendation for use of tricyclic antidepressants (TCAs), α2δ-ligands, and serotonin and norepinephrine reuptake inhibitors (SNRIs) as first-line treatments; a weak recommendation for capsaicin 8% patches, capsaicin cream, and lidocaine 5% plasters as second-line recommendation; and a weak recommendation for botulinum toxin (BTX-A), repetitive transcranial magnetic stimulation (rTMS), and opioids as third-line treatments for neuropathic pain.1

Specifically, TCAs had an NNT of 4.6 (95% CI, 3.2-7.7) and an NNH of 17.1 (95% CI, 11.4-33.6; moderate certainty of evidence), α2δ-ligands had an NNT of 8.9 (95% CI, 7.4-11.0) and an NNH of 26.2 (95% CI, 20.4-36.5; moderate certainty of evidence), SNRIs had an NNT of 7.4 (95% CI, 5.6–10.9) and an NNH of 13.9 (95% CI, 10.9–19.0; moderate certainty of evidence), BTX-A had an NNT of 2.7 (95% CI, 1.8–9.61) and an NNH of 216.3 (95% CI, 23.5–∞; moderate certainty of evidence), capsaicin 8% patches had an NNT of 13.2 (95% CI, 7.6–50.8) and an NNH of 1129.3 (95% CI, 135.7–∞; moderate certainty of evidence), opioids had an NNT of 5.9 (95% CI, 4.1–10.7) and an NNH of 15.4 (95% CI, 10.8–24.0; low certainty of evidence), rTMS had an NNT of 4.2 (95% CI, 2.3–28.3) and an NNH of 651.6 (95% CI, 34.7–∞; low certainty of evidence), capsaicin cream had an NNT of 6.1 (95% CI, 3.1–∞) and an NNH of 18.6 (95% CI, 10.6–77.1; very low certainty of evidence), and lidocaine 5% plasters had an NNT of 14.5 (95% CI, 7.8–108.2) and an NNH of 178.0 (95% CI, 23.9–∞; very low certainty of evidence).1

“It is necessary for health-care professionals to adapt these recommendations to their own contexts, to consider the cost and accessibility of each treatment, as well as individual patient values and preferences, to ensure their quality implementation in health care,” Soliman and colleagues concluded.1

REFERENCES

1. Soliman N, Moisset X, Ferraro MC, et al. Pharmacotherapy and non-invasive neuromodulation for neuropathic pain: a systematic review and meta-analysis. Lancet Neurol. 2025; 24(5); pp: 413-428. doi: 10.1016/S1474-4422(25)00068-7

2. Finnerup NB, Attal N, Haroutounian S, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. Lancet Neurol. 2015; 14(2); pp: 162-173. doi: 10.1016/S1474-4422(14)70251-0