Efficacy and safety of lacosamide in patients with trigeminal neuralgia: an 8-week pilot dose-escalation study

Background: Trigeminal neuralgia (TN) is a severe neuropathic pain condition in the orofacial region, with carbamazepine recommended as the first-line treatment. Nonetheless, its application is constrained by unfavorable drug responses and side effects. The objective of this research was to assess the effectiveness and safety of lacosamide, a third-generation anticonvulsant, in individuals with TN, and to juxtapose the findings with observational records from recently diagnosed TN patients who underwent carbamazepine monotherapy within the corresponding timeframe. Methods: An 8-week flexible dose titration of lacosamide was performed on newly diagnosed 12 TN patients who were divided into two groups: 200 mg/day (n = 5), and 400 mg/day (n = 7). Outcome measures included average pain score, Brief Pain Inventory-facial scores, and side effects. Patients were followed-up at 2, 4 and 8 weeks after baseline. Results: The percentage change of pain score at 4-week visit was compared between both lacosamide groups and patients receiving carbamazepine (n = 6) for four weeks during concurrent period. Both lacosamide groups experienced a decrease in pain score at 2-week follow-up, and differences in average pain score reduction were not observed between the two groups across all visits (p > 0.05). The mean Brief Pain Inventory-facial score in the lacosamide 200 mg/day group was higher than that in the 400 mg/day group at the 2-week follow-up (p = 0.03). Interestingly, the 4-week follow-up revealed that there were no significant variances in pain intensity between the lacosamide and the contemporaneous carbamazepine cohorts (p > 0.05). Frequently noted adverse events were mild somnolence (n = 9), slight vertigo (n = 5), and emotional lability (n = 2) without instances of severe adverse drug responses. Conclusions: Lacosamide demonstrates potential as a therapeutic option for patients suffering from trigeminal neuralgia. Clinical Trial Registration: TCTR20210811002.

Trigeminal neuralgia; Lacosamide; Carbamazepine; Brief pain inventory-facial

[1] Lambru G, Zakrzewska J, Matharu M. Trigeminal neuralgia: a practical guide. Practical Neurology. 2021; 21: 392–402.

[2] Ashina S, Robertson CE, Srikiatkhachorn A, Di Stefano G, Donnet A, Hodaie M, et al. Trigeminal neuralgia. Nature Reviews Disease Primers. 2024; 10: 39.

[3] Khawaja SN, Scrivani SJ. Trigeminal neuralgia. Dental Clinics of North America. 2023; 67: 99–115.

[4] Meng Q, Gu H, Zhang Q, Yi Z, Jiang D. Carbamazepine cutaneous adverse reactions and HLA gene variation in the Chinese population: a systematic review and meta-analysis. Pharmacogenomics. 2023; 24: 459–474.

[5] Nakkam N, Konyoung P, Amornpinyo W, Saksit N, Tiamkao S, Khunarkornsiri U, et al. Genetic variants associated with severe cutaneous adverse drug reactions induced by carbamazepine. The British Journal of Clinical Pharmacology. 2022; 88: 773–786.

[6] Koliqi R, Polidori C, Islami H. Prevalence of side effects treatment with carbamazepine and other antiepileptics in patients with epilepsy. Materia Socio-Medica. 2015; 37: 167–171.

[7] Díaz DV, Alvarado GG, Medina AL, Clavel JFG, Muñoz AG. Trigeminal neuralgia: therapeutic strategies to restore quality of life. Journal of Oral & Facial Pain and Headache. 2024; 38; 32–37.

[8] Sheets PL, Heers C, Stoehr T, Cummins TR. Differential block of sensory neuronal voltage-Gated sodium channels by lacosamide [(2R)-2-(Acetylamino)-N-benzyl-3-methoxypropanamide], lidocaine, and carbamazepine. The Journal of Pharmacology and Experimental Therapeutics. 2008; 326: 89–99.

[9] Bainbridge J, De Backer M, Eckhardt K, Tennigkeit F, Bongardt S, Sen D, et al. Safety and tolerability of lacosamide monotherapy in the elderly: a subgroup analysis from lacosamide trials in diabetic neuropathic pain. Epilepsia Open. 2017; 2: 415–423.

[10] Ziegler D, Hidvégi T, Gurieva I, Bongardt S, Freynhagen R, Sen D, et al. Efficacy and safety of lacosamide in painful diabetic neuropathy. Diabetes Care. 2010; 33: 839–841.

[11] de Greef BTA, Hoeijmakers JGJ, Geerts M, Oakes M, Church TJE, Waxman SG, et al. Lacosamide in patients with Nav1.7 mutations-related small fibre neuropathy: a randomized controlled trial. Brain. 2019; 142: 263–275.

[12] Lambru G, Stubberud A, Rantell K, Lagrata S, Tronvik E, Matharu MS. Medical treatment of SUNCT and SUNA: a prospective open-label study including single-arm meta-analysis. The Journal of Neurology, Neurosurgery, and Psychiatry. 2021; 92: 233–241.

[13] Adamo D, Coppola N, Pecoraro G, Nicolò M, Mignogna MD. Lacosamide in trigeminal neuralgia: report of a case refractory to first- and second-generation anticonvulsants. The Journal of Craniomandibular & Sleep Practice. 2023; 41: 126–130.

[14] Muñoz-Vendrell A, Tena-Cucala R, Campoy S, García-Parra B, Prat J, Martínez-Yélamos S, et al. Oral lacosamide for the treatment of refractory trigeminal neuralgia: a retrospective analysis of 86 cases. Headache. 2023; 63: 559–564.

[15] Muñoz-Vendrell A, Teixidor S, Sala-Padró J, Campoy S, Huerta-Villanueva M. Intravenous lacosamide and phenytoin for the treatment of acute exacerbations of trigeminal neuralgia: a retrospective analysis of 144 cases. Cephalalgia. 2022; 42: 1031–1038.

[16] Sandhu SK, Halpern CH, Vakhshori V, Mirsaeedi-Farahani K, Farrar JT, Lee JYK. Brief pain inventory-facial minimum clinically important difference. Journal of Neurosurgery. 2015; 122: 180–190.

[17] Shaibani A, Fares S, Selam J-L, Arslanian A, Simpson J, Sen D, et al. Lacosamide in painful diabetic neuropathy: an 18-week double-blind placebo-controlled trial. The Journal of Pain. 2009; 10: 818–828.

[18] Sarideechaigul W, Kitkhuandee A, Siritapetawee M, Butda P, Jorns TP. Profiling of patients presenting with trigeminal neuralgia and outcomes of medical management in a tertiary care center. The Journal of the Medical Association of Thailand. 2019; 102: 57.

[19] Tremont-Lukats IW, Megeff C, Backonja M-M. Anticonvulsants for neuropathic pain syndromes. Drugs. 2000; 60: 1029–1052.

[20] Turk DC, Dworkin RH, Allen RR, Bellamy N, Brandenburg N, Carr DB, et al. Core outcome domains for chronic pain clinical trials: IMMPACT recommendations. Pain. 2003; 106: 337–345.

[21] Nova CV, Zakrzewska JM, Baker SR, Riordain RN. Treatment outcomes in trigeminal neuralgia—a systematic review of domains, dimensions and measures. World Neurosurgery: X. 2020; 6: 100070.

[22] Ben‐Menachem E, Grebe HP, Terada K, Jensen L, Li T, De Backer M, et al. Long‐term safety and efficacy of lacosamide and controlled‐release carbamazepine monotherapy in patients with newly diagnosed epilepsy. Epilepsia. 2019; 60: 2437–2447.

[23] Yang C, Peng Y, Zhang L, Zhao L. Safety and tolerability of lacosamide in patients with epilepsy: a systematic review and meta-analysis. Frontiers in Pharmacology. 2021; 20: 694381.

[24] Shin Y-W, Moon J, Cho YW, Kim DW, Hong SB, Kim D-Y, et al. Tolerability of lacosamide rapid dose titration: a randomized, multicenter, prospective, open-label study. Epilepsy & Behavior. 2021; 115: 107663.

[25] Sunwoo J-S, Byun J-I, Lee SK. A case of lacosamide-induced hepatotoxicity. The International Journal of Clinical Pharmacology and Therapeutics. 2015; 53: 471–473.

[26] Kamitaki BK, Minacapelli CD, Zhang P, Wachuku C, Gupta K, Catalano C, et al. Drug-induced liver injury associated with antiseizure medications from the FDA Adverse Event Reporting System (FAERS). Epilepsy & Behavior. 2021; 117: 107832.

[27] Jeiziner C, Wernli U, Suter K, Hersberger KE, Meyer Zu Schwabedissen HE. HLA-associated adverse drug reactions—scoping review. Clinical and Translational Science. 2021; 14: 1648–1658.

[28] Sukasem C, Sririttha S, Chaichan C, Nakkrut T, Satapornpong P, Jaruthamsophon K, et al. Spectrum of cutaneous adverse reactions to aromatic antiepileptic drugs and human leukocyte antigen genotypes in Thai patients and meta-analysis. The Pharmacogenomics Journal. 2021; 21: 682–690.

[29] Verrotti A, Lattanzi S, Brigo F, Zaccara G. Pharmacodynamic interactions of antiepileptic drugs: from bench to clinical practice. Epilepsy & Behavior. 2020; 104: 106939.

[30] Campbell CM, Gilron I, Doshi T, Raja S. Designing and conducting proof-of-concept chronic pain analgesic clinical trials. Pain Report. 2019; 4: e697.