Safety and Efficacy of Lidocaine Versus Ketamine Infusion for Resistant Orofacial Pain

This Phase II, randomised, quadruple-masked, parallel trial (n=105) will evaluate the safety and efficacy of intravenous lidocaine, ketamine and a combined lidocaine–ketamine infusion in adults with treatment-resistant orofacial pain, with the primary outcome of pain reduction measured by the Visual Analog Scale (VAS). Interventions are lidocaine 5 mg/kg (max 500 mg) infused over 4 hours, ketamine 0.3 mg/kg infused over 4 hours, and a combined infusion of lidocaine 2.5 mg/kg plus ketamine 0.15 mg/kg infused over 4 hours. Participants will be randomised equally into three arms and receive their assigned slow intravenous infusion once weekly for three consecutive weeks with continuous cardiovascular and neurological/CNS monitoring during and after each infusion. Efficacy assessments occur at baseline, prior to the 2nd and 3rd infusions, and at 1, 3 and 6 months post-treatment; secondary measures include cortisol changes, depression assessment using PLAT‑Q and adverse event monitoring. Adults over 18 with orofacial pain refractory to standard therapies (including trigeminal neuralgia, TMJ dysfunction, malignant otitis externa, migraine or atypical facial pain) are eligible, and planned analyses include one-way ANOVA and repeated measures ANOVA for continuous outcomes.