Abstract
<title>Abstract</title> <p>Background Acute exacerbations of trigeminal neuralgia may require intravenous treatment when usual oral therapy is insufficient, but randomized comparative evidence is limited. This pilot trial aimed to estimate the efficacy and safety of intravenous lacosamide versus phenytoin and inform a definitive trial. Methods This single-center, prospective, randomized, open-label, parallel-group pilot trial was conducted in Mexico City. Adults aged ≥ 18 years with classical, secondary, or idiopathic trigeminal neuralgia, an acute exacerbation uncontrolled by usual oral therapy, and a requirement for intravenous treatment were eligible. Fifty-eight individuals were assessed and 57 were randomized 1:1 using sequentially numbered, opaque, sealed envelopes to lacosamide 200 mg intravenously over ≥ 15 minutes (n = 27) or phenytoin 15 mg/kg intravenously at ≤ 50 mg/min (n = 30). Participants, care providers, and outcome assessors were unblinded; the statistical analyst was blinded. The primary outcome was ≥ 50% reduction in pain intensity at 2 hours. All randomized participants were analyzed as assigned. Recruitment and 24-hour follow-up were completed in May 2026. Results At 2 hours, ≥ 50% pain reduction occurred in 25/27 participants (92.6%) receiving lacosamide and 27/30 (90.0%) receiving phenytoin (odds ratio [OR] 1.39, 95% confidence interval [CI] 0.21–9.01; p = 1.00). Complete pain freedom occurred in 9/27 (33.3%) versus 5/30 (16.7%) (p = 0.22), and rescue medication was required in 2/27 (7.4%) versus 6/30 (20.0%) (p = 0.26), respectively. Any adverse event occurred in 15/27 (55.6%) versus 28/30 (93.3%) participants (OR 0.09, 95% CI 0.02–0.45; p = 0.0015). No serious adverse events or treatment discontinuations occurred. Conclusions Both groups had high short-term response rates, but wide confidence intervals preclude definitive conclusions about comparative efficacy. Lacosamide was associated with fewer adverse events. These findings support a larger confirmatory randomized trial. Trial registration: ISRCTN92009764, registered July 22, 2026. Retrospectively registered.</p>