Slow-inactivated sodium channels as a therapeutic target in trigeminal neuralgia: evidence from a systematic review and meta-analysis of lacosamide

Background: Lacosamide (LCM), a selective enhancer of the slow inactivation of voltage-gated sodium channels, has been proposed as a treatment for trigeminal neuralgia (TN), although its clinical efficacy and safety remain incompletely defined. Methods: We conducted a systematic review and meta-analysis of cohort studies involving adults with TN. PubMed, EMBASE, and CENTRAL were searched from inception to 16 October 2025. The primary outcomes were efficacy, measured as pain relief, and safety, assessed by adverse events (AEs) associated with LCM. Results: Four studies were included in the quantitative synthesis. The pooled proportion of patients achieving pain relief with oral LCM was 66.7% (95% confidence interval (CI): 57.3%–74.9%; I2 = 0.0%). The pooled overall incidence of adverse events with oral LCM was 35.2% (95% CI: 26.8%–44.6%; I2 = 20.7%). The most frequently reported adverse event of oral LCM was sleepiness/somnolence (24.6%), followed by dizziness (21.7%), instability (2.5%), first-degree atrioventricular block (1.7%), and inattention (1.7%). All adverse events were infrequent and generally non-persistent. Additionally, intravenous LCM in acute exacerbation of TN reported that 77.8% of patients achieved patient-reported pain absence within 10 hours, with only 1.6% experiencing sleepiness. Conclusion: Lacosamide (LCM) has shown favorable outcomes in some patients with trigeminal neuralgia (TN) and may serve as an alternative therapy, particularly those refractory to or intolerant of first-line agents, and intravenous LCM may be useful for acute exacerbations. However, the current evidence is preliminary, observational, and insufficient to support comparative treatment decisions. Randomized controlled trials are needed to establish its efficacy and safety. The PROSPERO Registration: CRD420261295578.

Trigeminal neuralgia; Antiseizure medication; Lacosamide

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