The Changing Face of Trigeminal Neuralgia

A Narrative Review

Stine Maarbjerg MD, PhD; Rafael Benoliel BDS (Hons)


Headache. 2021;61(6):817-837. 

In This Article

Alternative and Future Pharmacotherapy for Classical Trigeminal Neuralgia174

Some nonantiepileptic or new drugs show promise in the management of CTN.[175] Pimozide is a centrally acting dopamine D2-receptor antagonist with evidence of efficacy that is greater than carbamazepine at 6 weeks.[176] Up to 83% of participants reported adverse effects, but these did not lead to withdrawal. Tizanidine is an alpha-2 adrenergic receptor agonist structurally related to clonidine and increases presynaptic inhibition of motor neurons. In a small trial, tizanidine was well tolerated, but the clinical effects were inferior to those of carbamazepine.[177] A later study revealed that patients experienced recurrence of TN within 1–3 months.[178]

Levetiracetam is an antiepileptic whose mechanism may involve inhibition of voltage-dependent N-type calcium channels, facilitation of GABA-ergic inhibitory transmission, reduction of delayed rectifier potassium current, and/or binding to synaptic proteins that modulate neurotransmitter release. Refractory CTN cases were treated with levetiracetam (3–4 g/day) as add-on therapy and experienced a reduction in the number of daily attacks by 62.4%. However, seven of the 23 patients withdrew from the study due to side effects.[179] The results in patients with central pain due to MS or with painful polyneuropathy were disappointing and therefore the potential of levetiracetam in neuropathic pain management is unclear.[180,181] Lacosamide is a functionalized amino acid whose precise antiepileptic mechanism is unknown. It enhances sodium channel inactivation, normalizes activation thresholds, decreases pathophysiological neuronal activity, and is beneficial in animal models of neuropathic pain.[182] Lacosamide has a modest effect in painful diabetic neuropathy, but increasing dosages induced significant side effects with little clinical benefit.[183] Early clinical findings suggest some benefit for refractory patients with CTN.[184] Eslicarbazepine is an AED that targets voltage-gated sodium channels. In a retrospective, open-label, multicenter, intention-to-treat study, 18 patients with TN were studied. The dose of eslicarbazepine ranged between 200 and 1200 mg/day and attained a response rate of 88.9% with 71% of patients reporting adverse events and 22% of patients discontinuing treatment.[185]

A new Nav1.7 selective state-dependent, sodium channel blocker (vixotrigine) has been developed.[186] Nav1.7, a major sodium receptor in the nociceptive system, is not located in the brain, thus preventing any side effects associated with depression of CNS excitability.[187] Vixotrigine demonstrates good tolerability at therapeutic doses, time to treatment failure, number of paroxysms, and average daily pain score. The new drug was well tolerated, and no severe or serious adverse events were reported.[188]