An update on pharmacotherapy for trigeminal neuralgia

ABSTRACT

Introduction

Trigeminal neuralgia is a rare condition that can be effectively treated by carbamazepine or oxcarbazepine but these older drugs are associated with dose-dependent and potentially treatment-limiting adverse effects. Third-generation anticonvulsants, new calcitonin gene-related peptide blockers for migraine, and older drugs such as ketamine and cannabinoids may be promising adjuvants or monotherapeutic options.

Areas Covered

The new drugs, their presumed mechanisms of action, safety and efficacy are discussed herein. There is a paucity of robust clinical evidence in support of these drugs for trigeminal neuralgia. New migraine agents are considered as well although migraines and trigeminal neuralgia are distinct, albeit similar, conditions. No new drugs have been released to market in recent years with the specific indication of trigeminal neuralgia.

Expert opinion

In real-world clinical practice, about half of trigeminal neuralgia patients take more than one agent for prevention and combination therapy may be the optimal approach. Combination therapy might allow for lower doses of carbamazepine or oxcarbazepine, thus reducing the number and severity of potential adverse events but the potential for pharmacokinetic drug-drug interactions must be considered. Drug therapy for trigeminal neuralgia involves acute or abortive treatments, often administered in hospital versus long-term preventive therapy, usually involving oral agents.

Plain Language Summary

Trigeminal neuralgia is a relatively rare condition that usually affects one side of the face below the eye around the cheekbone. The cause of trigeminal neuralgia is sometimes a damaged nerve or a nerve that has lost part of its outer protective sheath (myelin). However, trigeminal neuralgia may have other neurological causes as well. Pain can be triggered by touch, pressure, or chewing and it tends to occur in very painful brief attacks followed by pauses with little or no pain. There are two types of drug treatment for trigeminal neuralgia: drugs to stop an ongoing attack (which are often administered in an emergency room or hospital intravenously) and drugs that are taken orally over the long term to reduce or prevent attacks.

The two most effective drugs for trigeminal neuralgia are carbamazepine and oxcarbazepine, which are actually drugs to prevent seizures. They are effective in reducing the pain intensity and number of attacks of trigeminal neuralgia but they have side effects. In fact, these side effects can be so severe that people stop taking the drugs.

Many new drugs have come to market recently that may work for trigeminal neuralgia, although none was specifically developed for this use. The newest generation of anti-seizure medications including eslicarbazepine, lacosamide, levetiracetam, and retigabine, may be just as effective as the older carbamazepine and oxcarbazepine drugs with fewer side effects. Clinical studies are needed to test them in trigeminal neuralgia patients but their mechanisms of action suggest that they might work well.

There are some new drugs developed for migraine headache that inhibit a substance in the body called CGRP. Migraine headaches and trigeminal neuralgia have some of the same symptoms but they are different conditions but both involve too much CGRP.

Other new drugs include lasmiditan, pimozide (used for Tourette syndrome), tizanidine (muscle relaxant), lamotrigine and vixotrigine (anti-seizure drugs) may also be beneficial. It may be that people with trigeminal neuralgia will have to take combination therapy, the use of two or more drugs with different mechanisms of action. Older drugs like ketamine and cannabinoids are also being considered as possible add-on agents for therapy for trigeminal neuralgia.

KEYWORDS:

• Calcitonin gene-related peptide antagonists
• eslicarbazepine
• lamotrigine
• lacosamide
• levetiracetam
• pimozide
• trigeminal neuralgia
• zavegepant

Article highlights

• First-line treatments for trigeminal neuralgia remain limited to the older sodium-channel blockers carbamazepine (most effective) and oxcarbazepine although these drugs have treatment-limiting side effects. These side effects are dose dependent.

• In real-world clinical practice, adjuvant agents are often used to reduce the dose of carbamazepine or oxcarbazepine, but there is little prescribing guidance in the literature for optimal drug combinations. Both carbamazepine and oxcarbazepine have numerous pharmacokinetic drug-drug interactions with drugs common for this indication.

• Third-generation antiseizure medications such as eslicarbazepine, retigabine, and lacosamide are promising; the latter may be effective in both abortive and prophylactic treatments.

• Drugs that inhibit calcitonin gene-related peptides (CGRP) have revolutionized migraine care but their applicability to trigeminal neuralgia is not established but is plausible.

• Other new agents of interest include lasmiditan, pimozide, tizanidine, lamotrigine, and vixotrigine. There are case studies and a few small clinical studies in the literature, but there is no body of robust research in support of these agents specifically for trigeminal neuralgia, a relatively rare condition.

Declaration of interest

JV Pergolizzi is a consultant, speaker, owner and/or researcher for Spirify Pharma, Salix, Enalare Therapeutics, Neumentum, Advantx Pharmaceuticals, NEMA Research, Innocan Pharmaceuticals and Bridge Therapeutics. JA LeQuang is a consultant and/or medical writer for NEMA Research, Neumentum and BIOTRONIK. M Wagner is a consultant for NEMA Research. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.