Trigeminal Neuralgia Medication
- Author: Manish K Singh, MD; Chief Editor: Robert A Egan, MD more...
Carbamazepine remains the criterion standard, but a number of other drugs have been used for a long time and with fair success in trigeminal neuralgia (TN). These agents should be considered successively in case of resistance. Rarely, combination therapy can be provided, but it should remain exceptional for tolerance reasons and because a synergistic effect rarely occurs. Duration of treatment depends on clinical evolution but usually is long term, often lasting years. Topical analgesics have failed in patients with ophthalmologic manifestations of trigeminal neuralgia.
Anticonvulsant drugs reduce the excitability of gasserian ganglion neurons, preventing anomalous discharges and related lancinating volleys of pain. Thus, these agents may help control paroxysmal pain by limiting the aberrant transmission of nerve impulses and reducing the firing of nerve potentials in the trigeminal nerve.
Carbamazepine is the criterion standard in the medical management of trigeminal neuralgia. A 100-mg tablet may produce significant and complete relief within 2 hours, and, for this reason, a 100 mg twice a day (bid) prescription is suitable to start. If this initial dose fails, one may push the dose to 1200 mg daily (qd), as the patient will tolerate, for initial relief; maintenance doses generally are lower, 100-800 mg daily bid. If using the extended-release caplet, begin with 200 mg qd and increase as needed to a maximum dose of 1200 mg/d bid. Titrating slowly improves tolerance.
So immediate, predictable, and powerful is the relief that if the patient does not respond at least partially to carbamazepine, one should reconsider the diagnosis of idiopathic trigeminal neuralgia. Note, however, that 15% of patients do not benefit from carbamazepine, forcing trials of other medications.
Small, uncontrolled studies have indicated possible effectiveness of gabapentin in patients whose pain has become refractory to carbamazepine. This agent is often better tolerated than carbamazepine by elderly patients. No placebo-controlled studies have been published, but several open trials have reported an improvement on this drug.
As for other indications, an adequate dosage seems to vary greatly, and a trial should include raising the dose (eg, 3600 mg/d) as long as no efficacy is yet encountered, before stopping it.
Lamotrigine provided sustained relief in 2 small prospective studies. In an open-label design by Lunardi et al, all 5 patients with symptomatic trigeminal neuralgia associated with multiple sclerosis (MS) and 10 of 15 patients with idiopathic disease gained complete relief when followed for 3-8 months. Doses varied widely from 100-400 mg/d.
In a double-blind, placebo-controlled, crossover study, Zakrzewska et al found 400 mg of lamotrigine relieved the pain in 7 of 13 patients with trigeminal neuralgia compared with only 1 of 14 on placebo.
The adverse event to prevent is a rash, sometimes severe and life threatening, mostly if titration is too rapid.
Phenytoin has a similar mechanism of action to carbamazepine but is probably less effective. Phenytoin may provide relief as an add-on drug when carbamazepine monotherapy wanes, as commonly happens after 1 or several years. This drug has several common adverse effects, which are often troublesome in older patients, and drug levels do not always correlate with efficacy.
This therapy is experimental. In a pilot study of 3 patients enrolled in a National Institutes of Health (NIH)–sponsored trial, investigators could not confirm the benefits of topiramate. However, it may be a reasonable second-line agent.
Zvartau-Hind et al reported success in an uncontrolled, open-label trial of 200-300 mg daily in 6 patients with multiple sclerosis (MS), prescribed as monotherapy (in 5 of the 6 individuals) over a 6-month interval. All 6 patients reported complete relief and appeared to tolerate the drug well. Solaro et al found 150-300 mg total daily doses relieved all trigeminal neuralgia pains in a case series of 4 patients, 2 with multiple sclerosis, 1 with idiopathic trigeminal neuralgia, and 1 with previous arteriovascular malformation resection, when followed for 6 months. Carbamazepine and gabapentin had previously failed in all patients.
Oxcarbazepine is a close cousin of carbamazepine and presumably works on similar mechanisms. This agent offers a better tolerance and is easier to manage. Studies are limited, as opposed to the large body of high-level evidence with carbamazepine.
Daily maintenance doses of oxcarbazepine 400-2400 mg/d were effective in several small uncontrolled studies. Three small, multicenter, double-blind randomized trials found it as efficacious as carbamazepine in newly diagnosed or refractory trigeminal neuralgia and to be better tolerated.
The recommended starting dose is 300 mg bid. Note that this drug has not yet been approved by the US Food and Drug Administration (FDA) for trigeminal neuralgia.
This drug has not yet been approved by the FDA for trigeminal neuralgia (TN).
Skeletal Muscle Relaxants
Several small, uncontrolled studies in the 1970s and 1980s, including those by Parekh et al and Fromm et al, demonstrated effectiveness of baclofen, particularly when added to an existing regimen of carbamazepine that is not providing adequate pain control. Once baclofen is added to an anticonvulsant, the dosage of the anticonvulsant often can be reduced.
Baclofen is the only medication in this class with published data to support efficacy. This drug may induce hyperpolarization of afferent terminals and inhibit both monosynaptic and polysynaptic reflexes at the spinal level.
Baclofen is most often used after therapy with carbamazepine has been initiated, and its effects may be synergistic with those of carbamazepine.
Tricyclic antidepressants are a complex group of drugs that have central and peripheral anticholinergic effects, as well as sedative effects. They have central effects on pain transmission and block the active reuptake of norepinephrine and serotonin.
A minority of patients might respond to amitriptyline. Anticholinergic adverse effects are the limitation.
Toxins are a relatively recent experimental approach to management of trigeminal neuralgia and have been mentioned to respond to patient inquiries. These agents are not recommended because of scant evidence of efficacy. The mechanism of action of these agents remains unclear, but they appear to potentially decrease painful afferents.
Subcutaneous injections of botulinum toxin have been beneficial in a pilot study of patients with ophthalmologic manifestations of trigeminal neuralgia, but these results await confirmation.
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|Condition||Male:Female Ratio||Age of onset, y||Localization||Accompanying Symptoms||Attack Duration||Cycles||Provocation|
|Trigeminal neuralgia||1:2||>50||Unilateral||None||Seconds||Month intervals||Trigger zones|
|Cluster headache||31:1||30-40||Always unilateral||Horner syndrome, conjunctival injection, epiphora||15-180 minutes||Clusters with weeks to months intervals||Nocturnal attacks|
|Migraine||1:1||10-20||Variable||Photophobia, phonophobia, gastrointestinal symptoms||4-72 hours||Days to weeks intervals||Variable|
|Feature||Trigeminal Neuralgia||Atypical Facial Pain|
|Main location||Trigeminal area||Face, neck, ear|
|Pain duration||Seconds to 2 minutes||Hours to days|
|Character||Electric jerks, stabbing||Throbbing, dull|
|Pain intensity||Severe||Mild to moderate|
|Provoking factors||Light touch, washing, shaving, eating, talking||Stress, cold|
|Associated symptoms||None||Sensory abnormalities|