Novel Therapies in Trigeminal Neuralgia: A Narrative Review

Abstract

Background: Trigeminal neuralgia (TN) is a severe neuropathic pain disorder for which treatment remains largely dependent on sodium-channel blockers. Although carbamazepine and oxcarbazepine are effective initially, adverse effects and treatment failure drive the search for novel therapies. Objective: To review emerging therapies for TN according to their level of clinical evidence and identify barriers to translation. Methods: PubMed, Embase, the Cochrane Library and ClinicalTrials.gov were searched for literature on emerging pharmacological, neuromodulatory and molecular therapies in TN and trigeminal neuropathic pain. Findings: Botulinum toxin type A has the strongest clinical evidence among novel therapies, with randomized trials demonstrating pain reduction. Sodium-channel approaches have produced mixed results, with vixotrigine failing its phase 2a endpoint, while the selective Nav1.8 inhibitor suzetrigine has not been studied in TN. A randomized trial of erenumab targeting CGRP was negative. Neuromodulation, including transcranial magnetic stimulation, peripheral stimulation and deep brain stimulation, remains supported mainly by small studies. Cannabinoid, gene-transfer and glial-directed therapies remain largely preclinical. Conclusion: Despite expanding understanding of TN pathophysiology, translation into effective novel treatments remains limited. Diagnostic heterogeneity and methodological challenges continue to impede progress. Future research should prioritize mechanism-based trials and better patient stratification.