Assessing the efficacy of trigeminal nerve stimulation for drug-resistant epilepsy: A systematic review and...

The management of drug-resistant epilepsy (DRE) is challenging as the conventional anti-epileptic drugs have failed to control seizures in these patients. In recent years, neuromodulation therapies have gained attention, specifically trigeminal nerve stimulation(TNS) for seizure control has emerged as an effective therapeutic option. However, its precise effectiveness, particularly as measured by response rates and seizure reduction rates, remains debated. In accordance with PRISMA guidelines, we performed a meta-analysis of the existing original studies across PubMed, SCOPUS, Cochrane, and Web of Science medical databases from inception to 31 October 2024. We aimed to include studies discussing trigeminal nerve stimulation, to evaluate the efficacy and safety of TNS in managing DRE. A total of 9 eligible studies were included. Our meta-analysis included nine studies with a total of 411 patients. Pooled analysis of double-arm studies demonstrated that TNS significantly increased the response rate at 3 months (RR 2.03, 95% CI [1.07, 3.84], P-value for effect = 0.03). The effect was not significant at 6 or 12 months (6 months: RR 3.00, 95% CI [0.41, 21.98], P-value for effect = 0.28; 12 months: RR 3.24, 95% CI [0.39, 26.97], P-value for effect = 0.28). TNS showed borderline statistical significance reduction in seizure frequency compared to sham at 3 months (RR 2.85,95%CI[0.99,8.22], P = 0.05). The effect was not significant at 6 or 12 months (6 months: RR 3.01,95% CI[0.44, 20.58], P = 0.26; 12 months: RR 3.26,95%CI[0.38,27.68], P = 0.28). In single-arm analysis, the pooled proportion of patients achieving a response (≥ 50% seizure reduction) was 42% (95% CI: 30% to 54%) at 3 months, 48% (95% CI: 36% to 61%) at 6 months, and 45% (95% CI: 30% to 60%) at 12 months. The mean percentage seizure reduction was 29% (95% CI: 8% to 51%) at 3 months, 40% (95% CI: 28% to 52%) at 6 months, and 46% (95% CI: 29% to 62%) at 12 months. This meta-analysis provides evidence supporting TNS as a well-tolerated therapy with a statistically significant short-term effect at 3 months. Point estimates at 6 and 12 months suggest potential long-term benefit, but the evidence is fragile due to imprecise and wide confidence intervals. Larger randomized trials are needed to confirm the long-term efficacy of TNS for DRE.