TRICYCLIC antidepressants (TCAs) and non-invasive neuromodulation techniques like repetitive transcranial magnetic stimulation (rTMS) demonstrate the highest efficacy for neuropathic pain, with TCAs achieving a number needed to treat (NNT) of 4.6, according to a comprehensive meta-analysis of 313 trials involving 48,789 participants.
Neuropathic pain remains a complex clinical challenge due to limited treatment efficacy and significant side effects. Updated recommendations from the Neuropathic Pain Special Interest Group (NeuPSIG), incorporating new pharmacological and neuromodulation evidence, aim to refine therapeutic strategies. This systematic review and meta-analysis evaluated 284 pharmacological and 29 neuromodulation trials, focusing on double-blind, placebo-controlled studies to reassess first- to third-line treatments.
The analysis revealed strong recommendations for TCAs (NNT=4.6, 95% CI 3.2–7.7), α2δ-ligands (gabapentin/pregabalin; NNT=8.9), and serotonin-norepinephrine reuptake inhibitors (SNRIs; NNT=7.4) as first-line options due to moderate certainty of efficacy and safety. Second-line weak recommendations included capsaicin 8% patches (NNT=13.2) and lidocaine 5% plasters (NNT=14.5), while third-line options featured botulinum toxin (NNT=2.7) and rTMS (NNT=4.2). Opioids, though effective (NNT=5.9), received a weak third-line recommendation due to low safety certainty (NNH=15.4). Neuromodulation techniques like rTMS showed promise but require further validation.
These findings underscore the importance of prioritising TCAs and SNRIs in clinical practice, while advocating cautious opioid use. Future research should focus on long-term efficacy trials, personalised treatment algorithms, and integrating neuromodulation into standard care pathways. Clinicians are encouraged to adopt a stratified approach, combining pharmacological and non-invasive methods to optimise outcomes in this heterogeneous patient population.
Reference
Soliman N et al. Pharmacotherapy and non-invasive neuromodulation for neuropathic pain: a systematic review and meta-analysis. The Lancet Neurology. 2025;24(5):413-28.
