Effectiveness and Tolerability of Topical Amitriptyline 10% Plus Lidocaine 2% Gel in Adults With Post‐Traumatic Trigeminal Neuropathic Pain: A Real‐World Evidence Study

BACKGROUND: Post-traumatic trigeminal neuropathic pain (PTNP) is a debilitating orofacial pain disorder most commonly caused by trigeminal nerve injury after dental procedures or facial trauma. Available systemic therapies have modest and inconsistent efficacy, with substantial tolerability concerns limiting adherence. OBJECTIVES: To evaluate the real-world effectiveness and tolerability of a compounded intraoral mucoadhesive gel containing amitriptyline 10% plus lidocaine 2% in adults with PTNP. METHODS: This retrospective real-world evidence study included adults with PTNP meeting ICHD-3/ICOP criteria who were treated at a tertiary orofacial pain clinic from May 1, 2023, to April 30, 2024. The primary outcome was the within-patient change in pain intensity on a 0-10 numerical rating scale (NRS) from baseline to week 8. Secondary outcomes included responder rates (≥ 50% and ≥ 30% pain reduction), patient global impression of improvement (PGI-I) and adverse events (AEs). RESULTS: Of 94 patients identified, 40 were included in the complete-case initiator cohort. Mean pain intensity decreased from 6.3 ± 1.7 at baseline to 3.0 ± 2.7 at week 8, corresponding to a mean within-patient reduction of 3.30 points (95% CI, 2.51-4.09; p < 0.001). Twenty-two of 40 patients (55%; 95% CI, 40-69) achieved a ≥ 50% reduction in pain intensity, and 27 of 40 (68%; 95% CI, 52-80) achieved a ≥ 30% pain reduction. Seventy-five percent (30/40, 95% CI, 60-86) reported overall improvement on the PGI-I. Mild treatment-related AEs occurred in five of 40 patients (12%); no serious AEs or treatment discontinuations were reported. CONCLUSION: In this retrospective real-world study, topical amitriptyline-lidocaine mucoadhesive gel was associated with statistically significant and clinically meaningful pain improvement in adults with PTNP, together with favourable tolerability. These findings support targeted mucosal delivery as a promising local therapeutic option and potential medication-sparing strategy, particularly when systemic therapies are ineffective or poorly tolerated. Randomized controlled trials are now needed to confirm efficacy and clarify the role of topical amitriptyline in PTNP treatment pathways and routine clinical care.